Wetherbee, James D.
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.
Following a series of acid mine drainage (AMD) projects funded largely by EPA’s Clean Water Act Section 319 non-point source program, the pH level in Aaron Run is meeting Maryland’s water quality standard – and the brook trout are back.
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).
Mishra, Bhoopesh; Haack, Elizabeth A; Maurice, Patricia A; Bunker, Bruce A
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 Cd2+ 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.
Vugts, Danielle J; Klaver, Chris; Sewing, Claudia; Poot, Alex J; Adamzek, Kevin; Huegli, Seraina; Mari, Cristina; Visser, Gerard W M; Valverde, Ibai E; Gasser, Gilles; Mindt, Thomas L; van Dongen, Guus A M S
All clinical 89 Zr-immuno-PET studies are currently performed with the chelator desferrioxamine (DFO). This chelator provides hexadentate coordination to zirconium, leaving two coordination sites available for coordination with, e.g., water molecules, which are relatively labile ligands. The unsaturated coordination of DFO to zirconium has been suggested to result in impaired stability of the complex in vivo and consequently in unwanted bone uptake of 89 Zr. Aiming at clinical improvements, we report here on a bifunctional isothiocyanate variant of the octadentate chelator DFO* and the in vitro and in vivo comparison of its 89 Zr-DFO*-mAb complex with 89 Zr-DFO-mAb. The bifunctional chelator DFO*-pPhe-NCS was prepared from previously reported DFO* and p-phenylenediisothiocyanate. Subsequently, trastuzumab was conjugated with either DFO*-pPhe-NCS or commercial DFO-pPhe-NCS and radiolabeled with Zr-89 according to published procedures. In vitro stability experiments were carried out in saline, a histidine/sucrose buffer, and blood serum. The in vivo performance of the chelators was compared in N87 tumor-bearing mice by biodistribution studies and PET imaging. In 0.9 % NaCl 89 Zr-DFO*-trastuzumab was more stable than 89 Zr-DFO-trastuzumab; after 72 h incubation at 2-8 °C 95 % and 58 % intact tracer were left, respectively, while in a histidine-sucrose buffer no difference was observed, both products were ≥ 92 % intact. In vivo uptake at 144 h post injection (p.i.) in tumors, blood, and most normal organs was similar for both conjugates, except for skin, liver, spleen, ileum, and bone. Tumor uptake was 32.59 ± 11.95 and 29.06 ± 8.66 % ID/g for 89 Zr-DFO*-trastuzumab and 89 Zr-DFO-trastuzumab, respectively. The bone uptake was significantly lower for 89 Zr-DFO*-trastuzumab compared to 89 Zr-DFO-trastuzumab. At 144 h p.i. for 89 Zr-DFO*-trastuzumab and 89 Zr-DFO-trastuzumab, the uptake in sternum was 0.92 ± 0.16 and 3.33 ± 0.32 % ID
de Garavilla, L.; Chermak, T.; Valentine, H.L.
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 completemore » 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.« less
Benz, Carina; Bull, Torill; Mittelmark, Maurice; Vaandrager, Lenneke
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. © The Author(s) 2014.
Library Journal, 2005
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…
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…
Technology Teacher, 2008
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…
Wiche, Oliver; Tischler, Dirk; Fauser, Carla; Lodemann, Jana; Heilmeier, Hermann
Effects of citric acid and desferrioxamine B (DFO-B) on the availability of Ge and selected rare earth elements (REEs) (La, Nd, Gd, Er) to Phalaris arundinacea were investigated. A soil dissolution experiment was conducted to elucidate the effect of citric acid and DFO-B at different concentrations (1 and 10 mmol L -1 citric acid) on the release of Ge and REEs from soil. In a greenhouse, plants of P. arundinacea were cultivated on soil and on sand cultures to investigate the effects of citric acid and DFO-B on the uptake of Ge and REEs by the plants. Addition of 10 mmol L -1 citric acid significantly enhanced desorption of Ge and REEs from soil and uptake into soil-grown plants. Applying DFO-B enhanced the dissolution and the uptake of REEs, while no effect on Ge was observed. In sand cultures, the presence of citric acid and DFO-B significantly decreased the uptake of Ge and REEs, indicating a discrimination of the formed complexes during uptake. This study clearly indicates that citric acid and the microbial siderophore DFO-B may enhance phytoextraction of Ge and REEs due to the formation of soluble complexes that increase the migration of elements in the rhizosphere.
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.
This essay addresses the reception of Karl Marx's writings among Russian Jewish revolutionaries in the 1870s. It explores the way Aaron Shemuel Lieberman (1843-1880), known as "the father of Jewish socialism," interpreted Marx through a kabbalistic prism. It argues that Jews were attracted to Marx in part because of the overlaps between historical materialism and certain strands of the kabbalistic tradition. It also sheds light on the early reception of Marx and the way his theory of revolution was reinterpreted to reflect the unique socio-economic conditions of the Russian Empire.
Kuban-Jankowska, Alicja; Sahu, Kamlesh K; Gorska-Ponikowska, Magdalena; Tuszynski, Jack A; Wozniak, Michal
Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2. ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity. We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Morin, Courtnie; Stanley, Candace
Building upon Kuh's (2008) research on high-impact educational practices, the authors interviewed Dr. Aaron Thompson to discuss effective implementation of these teaching and learning initiatives and the advancement of faculty development programming to support them. Dr. Thompson is the Interim President of Kentucky State University and Council on…
Price, Eric W; Carnazza, Kathryn E; Carlin, Sean D; Cho, Andrew; Edwards, Kimberly J; Sevak, Kuntal K; Glaser, Jonathan M; de Stanchina, Elisa; Janjigian, Yelena Y; Lewis, Jason S
The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as a 89 Zr-based immuno-PET imaging agent to noninvasively determine the local levels of HGF protein in tumors. Because recent clinical trials of HGF-targeting therapies have been largely unsuccessful in several different cancers (e.g., gastric, brain, lung), we have synthesized and validated 89 Zr-DFO-AMG102 as a companion diagnostic for improved identification and selection of patients having high local levels of HGF in tumors. To date, patient selection has not been performed using the local levels of HGF protein in tumors. Methods: The chelator p -SCN-Bn-DFO was conjugated to AMG102, radiolabeling with 89 Zr was performed in high radiochemical yields and purity (>99%), and binding affinity of the modified antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA)-type binding assay. PET imaging, biodistribution, autoradiography and immunohistochemistry, and ex vivo HGF ELISA experiments were performed on murine xenografts of U87MG (HGF-positive, MET-positive) and MKN45 (HGF-negative, MET-positive) and 4 patient-derived xenografts (MET-positive, HGF unknown). Results: Tumor uptake of 89 Zr-DFO-AMG102 at 120 h after injection in U87MG xenografts (HGF-positive) was high (36.8 ± 7.8 percentage injected dose per gram [%ID/g]), whereas uptake in MKN45 xenografts (HGF-negative) was 5.0 ± 1.3 %ID/g and a control of nonspecific human IgG 89 Zr-DFO-IgG in U87MG tumors was 11.5 ± 3.3 %ID/g, demonstrating selective uptake in HGF-positive tumors. Similar experiments performed in 4 different gastric cancer patient-derived xenograft models showed low uptake of 89 Zr-DFO-AMG102 (∼4-7 %ID/g), which corresponded with low HGF levels in these tumors (ex vivo ELISA). Autoradiography, immunohistochemical staining, and HGF ELISA assays confirmed that elevated levels of HGF protein were present only in U87MG tumors and that 89 Zr-DFO-AMG102 uptake was closely correlated
Frings, Jannik; Krause, Matthias; Akoto, Ralph; Wohlmuth, Peter; Frosch, Karl-Heinz
Valgus deformities of the lower extremity influence patellofemoral joint kinematics. However, studies examining the clinical outcome after treatment of patellar instability and maltracking due to valgus deformity are rare in recent literature. This study's purpose is to analyze the clinical results after combined distal femoral osteotomy (DFO) for treatment of patellar instability. From 2010 to 2016, 406 cases of patellofemoral instability and maltracking were treated. Twenty cases of recurring (≥ 2) patellar dislocations with genu valgum and unsuccessful conservative treatment were included in the study. A radiological analysis was performed, and anteroposterior (AP), lateral and long leg standing radiographs were analyzed, and the leg axis was pre- and postoperatively measured. At least 12 months postoperatively, the clinical leg axis, range of motion (ROM), apprehension sign, Zohlen sign, and J-sign were physically examined. Pain level and knee function were objectified on a visual analogue scale (VAS). The Lysholm, Kujala, and Tegner scores, re-dislocation rate, and patient satisfaction were also examined. 20 combined DFOs on 18 patients with a median age of 23 years (15-55 years) were performed. The preoperative mechanical leg axis was 6.5° ± 2.0° valgus, and the mean tibial tuberosity to trochlear groove (TT-TG) distance was 19.1 ± 4.8 mm. All patients reported multiple dislocations. Intraoperatively, 71% presented III°-IV° cartilage lesions, located retropatellarly in 87% and correlating negatively with the postoperative Lysholm score (r = - 0.462, p = 0.040). The leg axis was corrected by 7.1° ± 2.6°, and in 17 cases, the tibial tubercle was additionally medialized by 10 ± 3.1 mm. All patellae were re-stabilized with medial patellofemoral ligament reconstruction. After a median period of 16 (12-64) months, the pain level decreased from 8.0 ± 1.4 to 2.3 ± 2.1 (VAS p ≤ 0.001) and knee function
Paull, J D
Isaac Aaron (1804 to 1877), an ambitious young medical practitioner, arrived in Sydney from Britain in 1838 and was registered by the New South Wales Medical Board the following year. After contributing to the Australian Medical Journal, established in August 1846 by William Baker, he became the editor in December and acquired it in May the following year. Dr Pugh became the most prolific local contributor to the journal but he and the editor had a somewhat 'prickly' relationship. Aaron was very critical of etherisation when the first news arrived in Australia, but Pugh chose Aaron's journal in which to report his initial and subsequent experience with the technique. Aaron repeatedly appealed for experimental evidence and rational decision-making to determine the place of etherisation in medical practice. Unfortunately for Australian medicine, Aaron had to suspend the publication of the journal in October 1847, lacking both time and the support of the profession necessary to maintain it. This created an unanticipated adverse outcome for Dr Pugh.
... Buildings. DATES: There will be a public meeting held on December 6, 2010 from 9 a.m. to 5 p.m. (Eastern... 20005; telephone (202) 862-1600. FOR FURTHER INFORMATION CONTACT: Any member of the public wishing to obtain information concerning the public meeting may contact Mr. Aaron Yeow, Designated Federal Officer...
Hollingsworth, Sandra; And Others
A case study showed how a third-year teacher modified the socialized culture of literature-based literacy instruction she found in her second-grade classroom and teacher education program to reach particular children who were having difficulty learning to read and write. Aaron, the subject of the case study, was a second-grade African-American…
Todd Levin. "Wholesale Electricity Market Design with Increasing Levels of Renewable Generation . Evolution of Wholesale Electricity Market Design with Increasing Levels of Renewable Generation. Golden, CO
Energy Analysis Center. Areas of Expertise Environmental laws and regulations Energy facility siting and transmission laws and regulations Natural resource leasing and acquisition Legal impacts on renewable energy development Legal and policy research Research Interests Renewable energy and transmission project development
doping of III-Nitride materials grown by molecular beam epitaxy (MBE). He joined NREL after graduation in (0001) GaN Growth by Radio Frequency Plasma-Assisted Molecular Beam Epitaxy, A.J. Ptak, M.R. Millecchia . Phys. Lett. 77, 2479 (2000). Magnesium Incorporation in GaN Grown by rf-Plasma Assisted Molecular Beam
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
Rep. Lofgren, Zoe [D-CA-19
House - 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:
Koch, Tom; Denike, Ken
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…
Turan, Ihsan; Topaloglu, Ali Kemal; Yuksel, Bilgin
We appreciate the valuable comments on our article by Hanukoglu and Hanukoglu. With regard to cutaneous involvement in systemic pseudohypoaldosteronism (sysPHA), we agree with Hanukoglu and Hanukoglu in that these co-occurrences are not rare. Indeed, in our study, three of four patients with sysPHA1 showed skin manifestations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
... this Decision and Final Order based on relevant evidence contained in the record submitted by the... of Osteopathic Examiners in Medicine and Surgery (hereinafter, the Board), Registrant is without authority to practice medicine or handle controlled substances in the State of Arizona, the State in which...
... in the conduct of trade or business in order to prevent evasion of a denial order. Because Henderson... is necessary to avoid evasion of the denial order against Henderson. As provided in Section 766.23 of... entity related to Henderson would be necessary to prevent evasion of a denial order imposed against...
A brief review of the Advanced Technology Advisory Committee activities in preparation of the report to Congress on the potential for advancing automation and robotics technology is documented. The technology is to be used for the Space Station and the US economy. (BCS)
Reilly, Marie; Fogler, Jason; Bridgemohan, Carolyn; Wiley, Melora; Weitzman, Carol; Augustyn, Marilyn
Aaron is an 11-year-old boy with autism spectrum disorder (ASD), with cognitive and language skills in the above-average range, whose parents have recently separated. Aaron's mother initiated the separation when she learned that Aaron's father had maintained a relationship with a woman with whom he has a 10-year-old daughter. When Aaron's mother discovered this relationship, she demanded that Aaron's father leave their home.Aaron's father has moved in with his long-term girlfriend and keeps in contact with Aaron by calling once a day. Neither Aaron's father nor mother has discussed the reason for their separation with Aaron. So far, they have explained their separation by telling Aaron that they are "taking a break."Aaron's mother has been deeply hurt by Aaron's father's infidelity and does not want to reconcile with him. Aaron's father recognizes this but would like to continue to have a close relationship with his son. He would also like Aaron to get to know his half-sister.Aaron's mother seeks guidance regarding how to talk to Aaron about the separation and his father's second family. Given Aaron's diagnosis of ASD, she is particularly concerned about his ability to cope with this unexpected change in circumstances. What is your advice?
respecting their desire for self-determination. See Pressman , Jeffrey L. and Wildavsky, Aaron. Implementation. (Berkeley: University of California Press... Pressman , Jeffrey L. and Wildavsky, Aaron. Implementation. (Berkeley: University of California Press 1971). Sablan, Gregory. Developing
Saito, Takashi; Tabata, Yasuhiko
The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Faulkner, C.H.; McCollough, C.R.
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 Middlemore » 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.« less
Huang, Xi; Dai, Jisen; Huang, Chuanshu; Zhang, Qi; Bhanot, Opinder; Pelle, Edward
Deferoxamine (DFO) is a drug widely used for iron overload treatment to reduce body iron burden. In the present study, it was shown in mouse epidermal JB6 cells that all iron compounds transiently induced extracellular signal-regulated kinases (ERK) phosphorylation, whereas DFO further enhanced ERK phosphorylation over long periods. The ERK phosphorylation by DFO treatment appears to be due to the inhibition of MAPK phosphatases (MKP) by DFO. The combined effects of iron-initiated MAPK activation and DFO-mediated MKP inhibition resulted in a synergistic enhancement on AP-1 activities. The results indicate that the interplay between MAPK and MKP is important in regulating the extent of AP-1 activation. It is known that administration of DFO in iron overload patients often results in allergic responses at the injection sites. The results suggest that this synergistic AP-1 activation might play a role in DFO-induced skin immune responses of iron overload patients.
Siriwardana, Gamini; Seligman, Paul A
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.
Siriwardana, Gamini; Seligman, Paul A.
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
..., Introductions, and Administrative Remarks by Special Committee Leadership. Designated Federal Official (DFO): Mr..., DC, on June 15, 2012. Kathy Hitt, Program Analyst, Business Operations Branch, Federal Aviation...
...., Arlington, VA 22202. FOR FURTHER INFORMATION CONTACT: Fred Jenkins, Designated Federal Official (DFO... address: jenkins[email protected] . SUPPLEMENTARY INFORMATION: All other information provided in the February...
Hey, Spencer Phillips; Kesselheim, Aaron S
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.
Arantes, Jerusa Marilda; Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Silva, Maisa; Araújo, Márcio Sobreira Silva; de Carvalho, Andréa Teixeira; Pedrosa, Maria Lúcia; Carneiro, Cláudia Martins; Tafuri, Washington Luiz; Martins-Filho, Olindo Assis; Elói-Santos, Silvana Maria
Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties. Copyright © 2011 Elsevier Inc. All rights reserved.
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Management November-December 1991: 39-45. 13 Chubb, John E. and Eric A. Hanushek . Setting National Priorities: Policy for the Nineties. Ed. Henry J. Aaron...A. Hanushek . Setting National Priorities: Policy for the Nineties. Ed. Henry J. Aaron. Washington, D.C.: The Brookings Institution,1990. 16 ’Training
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…
through such personal interface, a strategic leader can facilitate the implementation of strategy. Jeffrey L. Pressman and Aaron Wildavsky have also...Way to Think About It, and a Way to Do it,” Military Review (March-April 2011):44-45. 18. Jeffrey L. Pressman and Aaron Wildavsky, Implementation: How
This article features two high school chemistry teachers, Aaron Sams and Jonathan Bergmann, who have overturned conventional classroom instruction by using video podcasts to form the root of a new learning model. Thumbing through an issue of "MacWorld" a few years ago, Aaron Sams was struck by an article about an application called ProfCast that…
LASER ASSISTED IN SITU KERATOMILEUSIS ( LASIK ) EYES Aaron MT, Gooch JM, Harvey RR, Davis RE, and Tutt RC Abstract: Aviation, Space, and Environmental...AZ; 9-13 May 2010 10. EFFECT OF HIGH ALTITUDE ON LASER ASSISTED IN SITU KERATOMILEUSIS ( LASIK ) EYES Aaron MT, Gooch JM, Harvey RR, Davis RE, and
, The Environmental Law Institute, Washington, D.C. (2014) Featured Publication Curtis, Taylor L., Aaron . Golden, CO: National Renewable Energy Laboratory. NREL/TP-6A20-70098. Levine, Aaron. Taylor L. Curtis . Golden, CO: National Renewable Energy Laboratory: NREL/TP-6A20-70121. Kevin B. Jones, Curtis, Taylor L
Morbey, Mary Leigh
Opening with a discussion of AARON, an artificial intelligence symbol system that is used to generate computer drawings, this document makes the argument that AARON is based upon a way of knowing that is abstract, analytical, rationalist and thus representative of the dominant, western, male philosophical tradition. Male bias permeates the field…
Bonham, George W.; And Others
Basic questions about foundations are addressed by George W. Bonham, an essay by James Douglas and Aaron Wildavsky is given, and responses are offered by the following people: Landrum R. Bolling, George W. Bonham, McGeorge Bundy, James Douglas, Fred M. Hechinger, John H. Knowles, Waldemar Nielsen, B. J. Stiles, Aaron Wildavsky, and Paul N.…
..., 2010. Docket Numbers: RP10-753-000. Applicants: Nexen Marketing, J. Aaron & Company. Description: Joint... Request for Expedited Consideration of Nexen Marketing U.S.A. Inc. and J. Aaron & Company. Filed Date: 05... interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov . To facilitate electronic...
Arano, Y.; Matsushima, H.; Tagawa, M.
A novel heterogeneous bifunctional reagent containing an ester bond, N-((4-(2-maleimidoethoxy)-succinyl)oxy)succinimide (MESS), was designed and synthesized for the conjugation of antibodies with the gallium-67 (67Ga) chelate of succinyldeferoxamine (SDF) via the ester bond. MESS was synthesized by the acylation of N-(2-hydroxyethyl)maleimide with succinic anhydride, followed by the activation of the resulting carboxylic acid to a succinimido ester. MESS possesses a maleimide group for protein conjugation and an active ester group for deferoxamine (DFO) coupling, and the two functional groups are linked via ester bonding. Conjugation of 67Ga-SDF with nonspecific human IgG was performed by reacting freshly thiolated IgG with the reactionmore » product of MESS and DFO, followed by 67Ga labeling of the resulting conjugate using GaCl3 (67Ga-DFO-MESS-IgG). For comparison, 67Ga-DFO conjugated nonspecific human IgG with a nonmetabolizable linkage was synthesized under the same conjugation conditions as those for 67Ga-DFO-MESS-IgG, using a nonmetabolizable heterogenous bifunctional reagent (N-((6-maleimidocaproyl)oxy)succinimide, EMCS) instead of MESS (67Ga-DFO-EMCS-IgG). HPLC size-exclusion chromatography of both preparations showed a single radioactivity and UV peak corresponding to the intact IgG. Generation of 67Ga-SDF from the 67Ga-DFO-MESS-IgG was demonstrated by reverse-phase HPLC analysis and cellulose acetate electrophoresis after the incubation of 67Ga-DFO-MESS-IgG in a buffered solution containing carboxyesterase. After injection of 67Ga-DFO-MESS-IgG into mice, faster radioactivity clearance from the blood and less radioactivity accumulation in the liver, kidney, and spleen was noted than when 67Ga-DFO-EMCS-IgG was injected.« less
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
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.
Fine, Jared M; Renner, Daniel B; Forsberg, Anna C; Cameron, Rachel A; Galick, Benjamin T; Le, Clint; Conway, Patrick M; Stroebel, Benjamin M; Frey, William H; Hanson, Leah R
In addition to the hallmark accumulation of amyloid and hyper-phosphorylation of tau, brain changes in Alzheimer's disease are multifactorial including inflammation, oxidative stress, and metal dysregulation. Metal chelators have been explored as a less well known approach to treatment. One chelator currently being developed is deferoxamine (DFO), administered via the intranasal (IN) route. In the current study, APP/PS1 amyloid mice were treated with a chronic, low dose of IN DFO, subjected to a rigorous battery of behavior tests, and the mechanism of action was examined. Mice were treated 3x/week with 0.24 C IN DFO for 18 weeks from 36 to 54 weeks of age, 4 weeks of behavior tests were performed that included both working and reference memory, anxiolytic and motor behaviors, and finally brain tissues were analyzed for amyloid, protein oxidation, and other proteins affected by DFO. We found that IN DFO treatment significantly decreased loss of both reference and working memory in the Morris and radial arm water mazes (p < 0.05), and also decreased soluble Aβ40 and Aβ42 in cortex and hippocampus (p < 0.05). Further, IN DFO decreased activity of GSK3β, and led to decreases in oxidative stress (p < 0.05). These data demonstrate that low doses of IN DFO can modify several targets along the multiple pathways implicated in the neuropathology of Alzheimer's, making it an attractive candidate for the treatment of this heterogeneous disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Otto-Duessel, Maya; Brewer, Casey; Gonzalez, Ignacio; Nick, Hanspeter; Wood, John C.
Introduction Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model. Methods Thirty-two female Mongolian gerbils 8–10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology. Results In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals. Conclusions Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model. PMID:19018129
Hidajat, Rudy R; McLay, Jan L; Goode, David H; Spearing, Ruth L
Iron overload caused by blood transfusion-dependent anaemia usually results in lethal cardiac toxicity unless treated by iron-chelation therapy. Chelation therapy with desferrioxamine (DFO) is well established and widely used to remove excess iron. Unfortunately, visual disorders have been recorded after DFO infusion. In this investigation, a 61-year-old Caucasian female received DFO for her autoimmune haemolytic anaemia. Prior to starting with the DFO treatment, her baseline ophthalmic screening and electrooculogram (EOG) were completely normal. Two years later she noticed a grey scotoma in her right eye. Visual acuity in this eye was reduced from 6/5 to 6/9 and funduscopy revealed evidence of non-specific mottling of the retinal pigment epithelium of both retinae. The EOG was flat (106%) in the right eye and subnormal in the left (155%). The lower limit of our EOG Arden Ratio for normal subjects is 180%. After her DFO treatment was stopped, her right visual acuity returned to 6/5, her field tests showed progressive improvement bilaterally and the EOG went back to the normal range. While waiting for splenectomy, the patient was restarted on a lower dose of DFO and EOG measurements were carried out every two (or three) weeks to monitor for DFO toxicity. The EOG varied during this period indicating some deterioration of function in the retinal pigment epithelium. However, normalisation of the EOG values (right = 217%, left = 217%) occurred after splenectomy and cessation of DFO therapy. Her visual function was normal and her visual acuity 6/4 bilateral when she was discharged from our outpatient clinic. On reviewing her history it was apparent that the EOG was the most sensitive indicator of DFO toxicity.
Rassu, Giovanna; Soddu, Elena; Cossu, Massimo; Brundu, Antonio; Cerri, Guido; Marchetti, Nicola; Ferraro, Luca; Regan, Raymond F.; Giunchedi, Paolo; Gavini, Elisabetta; Dalpiaz, Alessandro
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 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) and 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
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Xie, Lai-Hua; Doye, Angelia A; Conley, Eric; Gwathmey, Judith K
Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that our novel formulation lowered the dosage requirements by 50%-75%, allowed for less frequent and shorter treatment durations, eliminating the need for a pump and the standard multi-night administration of DFO. In an iron-overloaded rat model, LDFO reduced iron in the liver, and also improved cardiac function. The lower dosage and improved safety profile makes our novel LDFO delivery system a highly desirable new therapy. Meanwhile, this system will also provide an ideal model for studying the mechanism of Fe overload-induced arrhythmias. The political and economic factors related to health care disparities are also discussed.
Kanner, J; Harel, S
Desferrioxamine (DFO) involvement in several peroxidative systems was studied. These systems included: a) membranal lipid peroxidation initiated by H2O2-activated metmyoglobin (or methemoglobin); b) phenol-red oxidation by activated metmyoglobin or horseradish peroxidase (HRP): c) beta-carotene-linoleate couple oxidation stimulated by lipoxygenase or hemin. Desferrioxamine was found to inhibit all these systems but not ferrioxamine (FO). Phenol-red oxidation by H2O2-horseradish peroxidase was inhibited competitively with DFO. Kinetic studies using the spectra changes in the Soret region of metmyoglobin suggest a mechanism by which H2O2 reacts with the iron-heme to form an intermediate of oxy-ferryl myoglobin that subsequently reacts with DFO to return the activated compound to the resting state. These activities of DFO resemble the reaction of other electron donors.
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Banin, Ehud; Lozinski, Alina; Brady, Keith M.; Berenshtein, Eduard; Butterfield, Phillip W.; Moshe, Maya; Chevion, Mordechai; Greenberg, Everett Peter; Banin, Eyal
The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm infections where it shows tolerance to antibiotics. Here we report the novel use of a metallo-complex, desferrioxamine-gallium (DFO-Ga) that targets P. aeruginosa iron metabolism. This complex kills free-living bacteria and blocks biofilm formation. A combination of DFO-Ga and the anti-Pseudomonas antibiotic gentamicin caused massive killing of P. aeruginosa cells in mature biofilms. In a P. aeruginosa rabbit corneal infection, topical administration of DFO-Ga together with gentamicin decreased both infiltrate and final scar size by about 50% compared to topical application of gentamicin alone. The use of DFO-Ga as a Trojan horse delivery system that interferes with iron metabolism shows promise as a treatment for P. aeruginosa infections. PMID:18931304
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Guo, Chuang; Hao, Li-Juan; Yang, Zhao-Hui; Chai, Rui; Zhang, Shuai; Gu, Yu; Gao, Hui-Ling; Zhong, Man-Li; Wang, Tao; Li, Jia-Yi; Wang, Zhan-You
Accumulating evidence suggests that an abnormal accumulation of iron in the substantia nigra (SN) is one of the defining characteristics of Parkinson's disease (PD). Accordingly, the potential neuroprotection of Fe chelators is widely acknowledged for the treatment of PD. Although desferrioxamine (DFO), an iron chelator widely used in clinical settings, has been reported to improve motor deficits and dopaminergic neuronal survival in animal models of PD, DFO has poor penetration to cross the blood-brain barrier and elicits side effects. We evaluated whether an intranasal administration of DFO improves the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of dopaminergic neurons in the nigrostriatal axis and investigated the molecular mechanisms of intranasal DFO treatment in preventing MPTP-induced neurodegeneration. Treatment with DFO efficiently alleviated behavioral deficits, increased the survival of tyrosine hydroxylase (TH)-positive neurons, and decreased the action of astrocytes in the SN and striatum in an MPTP-induced PD mouse model. Interestingly, we found that DFO up-regulated the expression of HIF-1α protein, TH, vascular endothelial growth factor (VEGF), and growth associated protein 43 (GAP43) and down-regulated the expression of α-synuclein, divalent metal transporter with iron-responsive element (DMT1+IRE), and transferrin receptor (TFR). This was accompanied by a decrease in iron-positive cells in the SN and striatum of the DFO-treated group. We further revealed that DFO treatment significantly inhibited the MPTP-induced phosphorylation of the c-Jun N-terminal kinase (JNK) and differentially enhanced the phosphorylation of extracellular regulated protein kinases (ERK) and mitogen-activated protein kinase (MAPK)/P38 kinase. Additionally, the effects of DFO on increasing the Bcl-2/Bax ratio were further validated in vitro and in vivo. In SH-SY5Y cells, the DFO-mediated up-regulation of HIF-1α occurred via the activation of
Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina
This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.
cartilaginous tissue still present. DBM + L-DFO: Fracture gap less evident with more complete bone bridging with denser trabecular bone and less...fracture callus volume by micro-CT, and qualitative histology for callus tissue quality and vascularity in 5 groups (No implant, CS implant, DFO+CS...Weinhold, P. North Carolina Tissue Engineering and Regenerative Medicine Meeting, November 4, 2011; Winston Salem, NC. (presented) • Desferroxamine with
Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure. This study was designed to compare FSC and DFO head-to-head as bifunctional chelators for 89Zr-radiolabeled EGFR-targeting ZEGFR:2377 affibody bioconjugates. FSC-ZEGFR:2377 and DFO-ZEGFR:2377 were evaluated regarding radiolabeling, in vitro stability, specificity, cell uptake, receptor affinity, biodistribution, and microPET-CT imaging. Both conjugates were efficiently labeled with zirconium-89 at room temperature but radiochemical yields increased substantially at elevated temperature, 85 °C. Both 89Zr-FSC-ZEGFR:2377 and 89Zr-DFO-ZEGFR:2377 revealed remarkable specificity, affinity and slow cell-line dependent internalization. Radiolabeling at 85 °C showed comparable results in A431 tumor xenografted mice with minor differences regarding blood clearance, tumor and liver uptake. In comparison 89Zr-DFO-ZEGFR:2377, radiolabeled at room temperature, showed a significant difference regarding tumor-to-organ ratios. MicroPET-CT imaging studies of 89Zr-FSC-ZEGFR:2377 as well as 89Zr-DFO-ZEGFR:2377 confirmed these findings. In summary we were able to show that FSC is a suitable alternative to DFO for radiolabeling of biomolecules with zirconium-89. Furthermore, our findings indicate that 89Zr-radiolabeling of DFO conjugates at higher temperature reduces off-chelate binding leading to significantly improved tumor-to-organ ratios and therefore enhancing image contrast. PMID:29160082
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.
... spouse (when applicable); home and electronic mail addresses; work, home, cell telephone numbers; place... Tower, Suite 02G09, Alexandria, VA 22350-3100. Dated: November 21, 2012. Aaron Siegel, Alternate OSD...
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.
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.
... CONTACT: The point of contact for this notice is Ms. Dolores Hodge at (202) 685-0082, Fax (202) 685-3748 or Hodge[email protected] . Dated: April 30, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison...
... and open manner without fear of retribution or harassment in order to facilitate a just, thorough, and... retribution or harassment. Dated: November 12, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison...
Sinha, Michael S; Kesselheim, Aaron S
In a Guest Editorial, Aaron S. Kesselheim and Michael S. Sinha show how federal and state legislation to allow promotion of drugs for non-approved uses threatens to undermine the FDA's public health mission.
... Aaron, Stephanie and Melinda for keeping the household running when Melissa and Patricia drove 200 miles round ... to be able to ride a bike, roller blade, or hang on tightly to the playground equipment. ...
... industry position. From Blurred Lines to Guidelines for Myeloproliferative Neoplasms Dr. Aaron Gerds and Dr. Ruben Mesa summarize new NCCN guidelines for myeloproliferative neoplasms. A Woman With Hypergammaglobulinemia and Diffuse Lymphadenopathy Take ...
Aaron R. Turner
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
Aaron R. Turner
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
Hepinstall, S. E.; Maurice, P. A.; Miller, M. J.
Siderophores are metal-complexing ligands with high affinities for Fe(III), produced by many microorganisms in Fe-deficient environments. Siderophores can also form strong complexes with other metals such as Pb and Cd; hence, siderophores may play an important role in controlling metal mobility in porous media. This study compared the effects of siderophores desferrioxamine-B (DFO-B), desferrioxamine-D (DFO-D1), desferrioxamine-E (DFO-E), as well as siderophore-like ligand acetohydroxamic acid (aHA) on Pb and Cd adsorption to kaolinite (KGa-1b) at pH 4.5 to 9, in 0.1 M NaClO4, at 22 \\deg C, in the dark. At pH > 6.5 all of the siderophores plus aHA, inhibited Pb adsorption, with inhibition increasing in the order aHA < DFO-D1 < DFO-B < DFO-E. At lower pH, all four ligands slightly enhanced Pb adsorption. These ligands also inhibited Cd adsorption at high pH, but had little or no effect at low pH. These results suggest that siderophore effects on metal mobility through porous media are likely to be complex and variable with pH.
Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Hu, Huijin; Ye, Baodong; Zhou, Yuhong
Iron overload is commonly observed during the course of aplastic anemia (AA), which is believed to aggravate hematopoiesis, cause multiple organ dysfunction, lead to disease progression, and impair quality of life. Deferasirox (DFX) and deferoxamine (DFO) are among the most common iron chelation agents available in the clinical setting. The aim of this study was to investigate if the combination therapy with DFX and DFO is superior in hematopoietic recovery and iron chelation. Briefly, we developed a composite mouse model with AA and iron overload that was consequently treated with DFX, DFO, or with a combination of both agents. The changes in peripheral hemogram, marrow apoptosis, and its related protein expressions were compared during the process of iron chelation, while the iron depositions in liver and bone marrow and its regulator were also detected. The obtained results showed that compared to DFX, DFO has a better effect in protecting the bone marrow from apoptosis-induced failure. The combination of DFO and DFX accelerated the chelation of iron, while their efficiency on further hemogram improvement appeared limited. To sum up, our data suggest that single treatment with DFO may be a better choice for improving the hematopoiesis during the gradual chelation treatment irrespective of the convenience of oral DFX, while the combination treatment should be considered for urgent reduction of the iron burden.
Estrov, Z; Tawa, A; Wang, X H; Dubé, I D; Sulh, H; Cohen, A; Gelfand, E W; Freedman, M H
A six week old infant with acute leukemia failed to attain remission with chemotherapy. Because we previously demonstrated that the iron chelator deferoxamine (DFO) has antiproliferative properties and modulatory effects on cell differentiation, a protocol was designed for in vitro study and for clinical use in the patient. At diagnosis, blast cells were morphologically undifferentiated, had nondiagnostic cytochemistry, showed an abnormal karyotype (t[4;11]), expressed markers of B cell lineage, and demonstrated C mu gene rearrangement. Tissue culture of marrow or blood cells yielded colonies of leukemic blasts. Increasing concentrations of DFO produced a dose-dependent suppression of patient's blast colony growth in vitro, and blasts within colonies showed a marked change in surface antigen expression from lymphoid to myelomonocytic markers, became monocytic in appearance, and developed intense staining for nonspecific esterase. When DFO was given intravenously to the patient as a single agent for 48 hours, blasts no longer expressed lymphoid antigens and became strongly positive for myelomonocytic markers, identical to the in vitro findings. Intravenous DFO halted rising peripheral blood blast cell numbers and allowed a several-fold increase in normal hematopoietic progenitor colony growth. When combined with low-dose cytosine arabinoside in the treatment protocol, DFO caused striking leukemic cytoreduction. Our findings indicate that DFO has antileukemic properties by virtue of its effects on proliferation and differentiation, and they prompt further experimental and clinical studies with this agent.
Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D
Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.
Esparza, José L; Garcia, Tania; Gómez, Mercedes; Nogués, M Rosa; Giralt, Montserrat; Domingo, José L
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.
Cennamo, Nunzio; Alberti, Giancarla; Pesavento, Maria; D'Agostino, Girolamo; Quattrini, Federico; Biesuz, Raffaela; Zeni, Luigi
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
Cennamo, Nunzio; Alberti, Giancarla; Pesavento, Maria; D'Agostino, Girolamo; Quattrini, Federico; Biesuz, Raffaela; Zeni, Luigi
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.
Johani, K; Fritz, B G; Bjarnsholt, T; Lipsky, B A; Jensen, S O; Yang, M; Dean, A; Hu, H; Vickery, K; Malone, M
Rigorous visual evidence on whether or not biofilms are involved in diabetic foot osteomyelitis (DFO) is lacking. We employed a suite of molecular and microscopic approaches to investigate the microbiome, and phenotypic state of microorganisms involved in DFO. In 20 consecutive subjects with suspected DFO, we collected intraoperative bone specimens. To explore the microbial diversity present in infected bone we performed next generation DNA sequencing. We used scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with confocal microscopy to visualize and confirm the presence of biofilms. In 19 of 20 (95%) studied patients presenting with DFO, it was associated with an infected diabetic foot ulcer. By DNA sequencing of infected bone, Corynebacterium sp. was the most commonly identified microorganism, followed by Finegoldia sp., Staphylococcus sp., Streptococcus sp., Porphyromonas sp., and Anaerococcus sp. Six of 20 bone samples (30%) contained only one or two pathogens, while the remaining 14 (70%) had polymicrobial communities. Using a combination of SEM and PNA-FISH, we identified microbial aggregates in biofilms in 16 (80%) bone specimens and found that they were typically coccoid or rod-shaped aggregates. The presence of biofilms in DFO may explain why non-surgical treatment of DFO, relying on systemic antibiotic therapy, may not resolve some chronic infections caused by biofilm-producing strains. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Aaron married Harriet Collins. Though a happy and success- ful match, tragedy cut it short. Their first child, William Collins, was born in 1869, but... Harriet died giving birth to Josephine five years later. The widower needed a wife and his young children a mother, and so two years later Aaron married...For the events in Korea before 1950, see Leon Gordenker, The United Nations and the Peaceful Unification of Korea (The Hague: Martinus , 1959), Akira
W. Collins Peter Feiler John Goodenough Aaron Greenhouse Jorgen Hansson Alan R . Hevner John Hudak Angel Jordan Rick Kazman Richard C. Linger...John Goodenough Aaron Greenhouse Jorgen Hansson Alan R . Hevner John Hudak Angel Jordan Rick Kazman Richard C. Linger Mark G. Pleszkoch Stacy J...operability, sustainability, software R &D, metrics for acquisition, acquisition management, and commercial off-the-shelf products. The IR&D projects conducted
AWARD NUMBER: W81XWH-14-1-0277 TITLE: Studying Upper-Limb Amputee Prosthesis Use to Inform Device Design PRINCIPAL INVESTIGATOR: Aaron...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...Amputee Prosthesis Use to Inform Device Design 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Aaron Dollar, Adam Spiers
COMPUTER COMMUNICATIONS US A.RMY (CECOM) V September 1980 to August 1982 Principal Investigatoi Robert Boorstyn Aaron Kershenbaum DTIC Basil Niaglaris Philip...COMMUNICATIONS US ARMY (CECOM) September 1980 to August 1982 Principal Investigators: Robert Boorstyn Aaron Kershenbaum Basil Maglaris Philip Sarachik...TABLE OF CONTENTS Summary of Report Personnel Activities Research Reports / , A. Packet Radio Networks A.1 Throughput Analysis of Multihop Packet
learned and best practices. The Services appear to have insufficient data to assess traumatic stress and healthcare provider burnout , critical elements...Crisis Communication: Workplace and School Violence, Stockholm Syndrome , and Abnormal Psychology,” Annals of the American Psychotherapy Association...88-106; Matt DeLisi, Andy Hochstetler, Aaron M. Scherer, Aaron Purhmann, and Mark T. Berg, “The Starkweather Syndrome : Exploring Criminal History
NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS TRANSITIONING CLIENT- BASED NALCOMIS TO A MULTI-FUNCTION WEB- BASED APPLICATION by Aaron P...TITLE AND SUBTITLE TRANSITIONING CLIENT- BASED NALCOMIS TO A MULTI-FUNCTION WEB- BASED APPLICATION 5. FUNDING NUMBERS 6. AUTHOR(S) Aaron P. Schnetzler 7...NALCOMIS. NALCOMIS has two configurations that are used by organizational and intermediate level maintenance activi- ties, Optimized Organizational
CHOICES OF EARLY CAREER MARINES: A CHOICE ANALYSIS MODEL by André G. La Taste Aaron Masaitis March 2013 Thesis Advisor: Michael Dixon... ANALYSIS MODEL 5. FUNDING NUMBERS 6. AUTHOR(S) André G. La Taste, Aaron Masaitis 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate...system. The research will be conducted using a discrete choice analysis methodology that is often used to differentiate factors that lead to
Mario Marino Nitya Ranganathan Behnam Robatmili Aaron Smith James Burrill Stephen W. Keckler Doug Burger Kathryn S. McKinley Computer Architecture and...Marino, Nitya Ranganathan , Behnam Robatmili, Aaron Smith, James Burrill, Stephen W. Keckler, Doug Burger, Kathryn S. McKinley; ASPLOS 2009, Washington DC...aggressively register allo- cate more memory accesses by using programmer knowledge about pointer aliasing, much of which may be automated. They also
Arthur, Peter G; Niu, Xian-Wa; Huang, Wen-Hua; DeBoer, Bastiaan; Lai, Ching Tat; Rossi, Enrico; Joseph, John; Jeffrey, Gary P
AIM: To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage (CS) in a rat liver perfusion model. METHODS: Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4 °C, then exposed to 25 min of warm ischemia (WI) at 37 °C followed by 2 h of warm perfusion (WP) at 37 °C with oxygenated (95% oxygen and 5% carbon dioxide) Krebs-Henseleit buffer. Desferrioxamine (DFO), an iron chelator, was added at different stages of storage, ischemia and perfusion: in CS only, in WI only, in WP only, in WI and perfusion, or in all stages. Effluent samples were collected after CS and after WI. Perfusate samples and bile were collected every 30 min (0, 0.5, 1, 1.5 and 2 h) during liver perfusion. Cellular injury was assessed by the determination of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the effluent and perfusate samples. Total iron was analysed in the perfusate samples. After WP, the liver was collected for the determination of liver swelling (wet to dry ratio) and liver morphological examination (hematoxylin and eosin staining). RESULTS: Increased CS time caused increased liver dysfunction during WP. After 2 h of WP, liver injury was indicated by increased release of AST (0.5 h CS: 9.4 ± 2.2 U/g liver vs 20 h CS: 45.9 ± 10.8 U/g liver, P < 0.05) and LDH (0.5 h CS: 59 ± 14 U/g liver vs 20 h CS: 297 ± 71 U/g liver, P < 0.05). There was an associated increase in iron release into the perfusate (0.5 h CS: 0.11 ± 0.03 μmoL/g liver vs 20 h CS: 0.58 ± 0.10 μmoL/g liver, P < 0.05) and reduction in bile flow (0.5 h CS: 194 ± 12 μL/g vs 20 h CS: 71 ± 8 μL/g liver, P < 0.05). When DFO was added during WI and WP following 20 h of CS, release of iron into the perfusate was decreased (DFO absent 0.58 ± 0.10 μmoL/g liver vs DFO present 0.31 ± 0.06 μmoL/g liver, P < 0.05), and liver function substantially improved with decreased release of AST (DFO absent 45.9 ± 10.8 U
Rylova, Svetlana N; Del Pozzo, Luigi; Klingeberg, Cathrin; Tönnesmann, Roswitha; Illert, Anna L; Meyer, Philipp T; Maecke, Helmut R; Holland, Jason P
The CD30-specific antibody-drug conjugate, brentuximab vedotin, is approved for the treatment of relapsed, refractory Hodgkin lymphomas and systemic anaplastic large T-cell lymphomas. Multiple ongoing clinical trials are investigating brentuximab vedotin efficacy in other CD30-positive hematologic malignancies. Because CD30 expression varies among different types of lymphoma and can also change during the course of treatment, companion diagnostic imaging of CD30 could be a valuable tool in optimizing patient-specific brentuximab vedotin treatment regimens. The mouse antihuman CD30 antibody AC-10 was radiolabeled with the positron-emitting radionuclide (89)Zr. The stability and specificity of (89)Zr-desferrioxamine (DFO)-labeled CD30-specific AC-10 antibody ((89)Zr-DFO-AC-10) was evaluated in vitro. The pharmacokinetics of (89)Zr-DFO-AC-10 was studied in BALB/c nude mice bearing subcutaneous human Karpas 299 tumors (CD30-positive model) or A-431 tumors (CD30-negative model) using PET/CT imaging, biodistribution studies, and autoradiography. AC-10 was conjugated with a DFO B chelator and radiolabeled with (89)Zr to give formulated (89)Zr-DFO-AC-10 with a radiochemical yield of 80%, radiochemical purity greater than 99%, and specific activity of 111-148 MBq/mg. (89)Zr-DFO-AC-10 was stable in mouse and human sera and preserved the immunoreactivity toward CD30. Biodistribution data showed the highest tissue accumulation of (89)Zr-DFO-AC-10 in CD30-positive tumors, with 37.9% ± 8.2% injected activity per gram of tissue at 72 h after injection, whereas uptake in CD30-negative tumors was 11.0% ± 0.4%. The specificity of (89)Zr-DFO-AC-10 binding to CD30 in vivo was confirmed by blocking studies. Time-activity curves showed that between 24 and 144 h after injection, tumor-to-muscle ratios increased from 18.9 to 51.8 in the CD30-positive model and from 4.8 to 8.7 in the CD30-negative model. Tumor-to-blood ratios also increased, from 3.2 to 13.6 and from 1 to 2 in the CD30
Allahabadi, Sachin; Haroun, Kareem B.; Musher, Daniel M.; Lipsky, Benjamin A.; Barshes, Neal R.
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
Aydinok, Yesim; Unal, Sule; Oymak, Yesim; Vergin, Canan; Türker, Zeynep D; Yildiz, Dilek; Yesilipek, Akif
An observational study was conducted to explore postmarketing safety and efficacy of Deferasirox (DFX) in comparison with conventional Desferrioxamine (DFO) in chelation-naïve children with transfusional iron overload. Transfusion-dependent children (aged ≤ 5 yr) who had serum ferritin above 1000 μg/L and had been prescribed either first-line DFX or DFO for at least 12 months to maintain serum ferritin between 500 and 1000 μg/L were included. Initial DFX dose was 20 mg/kg/d for 7 d a week, and DFO dose was 25-35 mg/kg/d subcutaneously, given for 5 d a week. Dose adjustments were based on serum ferritin changes and safety markers. The primary efficacy endpoint was change in serum ferritin from baseline. The effect of transfusional iron loading rate (ILR) and different doses of chelators on serum ferritin was also assessed. A total of 111 patients were observed for a median of 2.29 yr on DFX (n = 71) and 2.75 yr on DFO (n = 40). Absolute change in serum ferritin from baseline to the last available observation was not significant with DFX (91 μg/L, P = 0.5) but significantly higher with DFO (385 μg/L, P < 0.005). ILR and DFX doses had a major impact on serum ferritin changes in DFX cohort. The height- and weight-standard deviation scores did not differ significantly in both cohorts during the study. Fluctuations in liver enzymes and non-progressive increase in serum creatinine were the most common adverse events (DFX; 9.8%, 18.0% and DFO; 5.0%, 7.5%, respectively). DFX is well tolerable and at least as effective as DFO to maintain safe serum ferritin levels and normal growth progression in chelation-naïve children. © 2012 John Wiley & Sons A/S.
Yu, Runhong; Wang, Dao; Ren, Xiuhua; Zeng, Li; Liu, Yufeng
The aim of this study is to investigate the growth-inhibitory and apoptosis-inducing effect of deferoxamine (DFO) combined with arsenic trioxide (ATO) on the human HL-60 xenografts in nude mice and its mechanism. The highly tumorigenic leukemia cell line HL-60 cells were inoculated subcutaneously into nude mice to establish a human leukemia xenograft model. The HL-60 xenograft nude mice models were randomly divided into four groups: control (Normal saline, NS), 50mg/kg DFO, 3mg/kg ATO, the combined treatment (50mg/kg DFO+1.5mg/kg ATO) once HL-60 cells were inoculated. Tumor sizes, growth curves, inhibitory rates, cell apoptosis, and the expression of apoptosis related markers were measured to evaluate the tumor growth. Xenografted tumors were observed in all nude mice since the 5th day of inoculation. The inhibitory rates of tumor weight were 2.67%, 10.69%, and 25.57% in DFO, ATO and combination therapy groups, respectively. The combination of DFO with ATO induces significantly more tumor cell apoptosis than either agent alone (p<0.05). The expression of NF-κBp65 and survivin proteins decreased significantly while the expression of Caspase-3 and Bax increased in the combination therapy group (p<0.05). Double immunofluorescence for Caspase-3 and NFκBp65 demonstrated an inverse relationship between Caspase-3-positive areas and NFκBp65-positive areas, as well as the co-localization of Bax and survivin in xenografted tumor cells. Combination of DFO and ATO has synergistic effects on tumor growth inhibition and apoptosis-inducing in vivo with no significant side effects. The DFO and ATO can up-regulate the expression of Caspase-3 and Bax, and down-regulate the expression of NF-κBp65 and survivin, especially for their combination. Copyright © 2014 Elsevier Ltd. All rights reserved.
Yao, Qingqing; Liu, Yangxi; Selvaratnam, Balaranjan; Koodali, Ranjit T; Sun, Hongli
Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF). Therefore, we developed a novel mesoporous silicate nanoparticles (MSNs) incorporated-3D nanofibrous gelatin (GF) scaffold for dual-delivery of BMP2 and deferoxamine (DFO). DFO is a hypoxia-mimetic drug that can activate hypoxia-inducible factor-1 alpha (HIF-1α), and trigger subsequent angiogenesis. Sustained BMP2 release system was achieved through encapsulation into large-pored MSNs, while the relative short-term release of DFO was engineered through covalent conjugation with chitosan to reduce its cytotoxicity and elongate its half-life. Both MSNs and DFO were incorporated onto a porous 3D GF scaffold to serve as a biomimetic osteogenic microenvironment. Our data indicated that DFO and BMP2 were released from a scaffold at different release rates (10 vs 28 days) yet maintained their angiogenic and osteogenic ability, respectively. Importantly, our data indicated that the released DFO significantly improved BMP2-induced osteogenic differentiation where the dose/duration was important for its effects in both mouse and human stem cell models. Thus, we developed a novel and tunable MSNs/GF 3D scaffold-mediated dual-drug delivery system and studied the potential application of the both FDA-approved DFO and BMP2 for bone tissue engineering. Copyright © 2018 Elsevier B.V. All rights reserved.
Cappellini, Maria Domenica; Bejaoui, Mohamed; Agaoglu, Leyla; Porter, John; Coates, Thomas; Jeng, Michael; Lai, Maria Eliana; Mangiagli, Antonio; Strauss, Gabriele; Girot, Robert; Watman, Nora; Ferster, Alina; Loggetto, Sandra; Abish, Sharon; Cario, Holger; Zoumbos, Nicolaos; Vichinsky, Elliott; Opitz, Herbert; Ressayre-Djaffer, Catherine; Abetz, Linda; Rofail, Diana; Baladi, Jean-Francois
Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries. This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670). PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication
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
Kim, Jinhyun; Kim, Younhee
This study aims to conduct an economic evaluation of oral deferasirox (DSX) compared with infusional deferoxamine (DFO) in patients with transfusional iron overload. Depending on the methods for measuring time-cost and convenience associated with the mode of administration, either cost-utility analysis or cost-effectiveness analysis was undertaken. The difference in compliance rate between DSX and DFO was applied. Although the drug cost of DSX was US$124,070 higher than that of DFO (US$96,039 vs. US$220,199), all other costs were lower in patients with DSX than in patients with DFO. In the cost-utility analysis, DSX resulted in US$3197 savings with a gain of 2.63 quality-adjusted life-years per patient. The result of the cost-effectiveness analysis also showed that DSX dominated DFO. With a considerable improvement in convenience and injection time rather than efficacy, DSX is considered as a dominant therapy for patients with iron overload.
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
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.
Bertagnolli, Ana Paula Coitino; Gubiani, Marileda Barichello; Ceron, Marizete; Keske-Soares, Márcia
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
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
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
Lázaro-Martínez, José Luis; Tardáguila-García, Aroa; García-Klepzig, José Luis
Diabetic foot osteomyelitis (DFO) is the most common infection associated to diabetic foot ulcers (DFU). This review is designed to provide an update on the diagnosis and treatment of DFO based on an analysis of MEDLINE through PubMed using as search criterion "Diabetic Foot Osteomyelitis". Authors have included in this review the most relevant manuscripts regarding diagnosis and treatment of DFO. After review and critical analysis of publications, it may be concluded that diagnosis of DFO is not simple because of its heterogeneous presentation. Clinical inflammatory signs, probe-to-bone test, and plain X-rays are postulated as the basic tests for clinical diagnosis when DFO is suspected. Diagnosis should be supported by laboratory tests, of which ESR (>70mm/h) has been shown to be most precise. MRI is the most accurate imaging test, especially for differential diagnosis with Charcot foot. Pathogen isolation by bone culture is essential when the patient is treated with ATB only. Medical or surgical treatment should be based on the clinical characteristics of the patient and the lesion. Surgery should always be an option if medical treatment fails. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Oberhensli, R.D.; Mueller, R.M.; Fridrich, R.
The contrast-enhancing properties of iron (Fe) and deferoxamine (DFO) in abscess imaging with Ga-67 citrate were compared in rats bearing turpentine-induced abscesses. Iron administration shifted Ga-67 from plasma into tissues such as muscle and fat. As a result, the abscess-to-plasma ratio increased whereas the abscess-to-muscle ratio decreased. DFO enhanced the abscess-to-muscle and abscess-to-plasma ratios by increasing urinary Ga-67 excretion. The authors conclude that abscess imaging with Ga-67 citrate may be improved by administration of (a) Fe for detection of abscesses masked by blood activity, or (b) DFO for detection of abscesses surrounded by muscle tissue.
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
Babcock, Jennifer; Herrera, Alberto; Coricor, George; Karch, Christopher; Liu, Alexander H.; Rivera-Gines, Aida; Ko, Jane L.
Cellular adaptation to hypoxia is a protective mechanism for neurons and relevant to cancer. Treatment with desferrioxamine (DFO) to induce hypoxia reduced the viability of human neuronal NMB cells. Surviving/attached cells exhibited profound increases of expression of the human kappa-opioid receptor (hKOR) and hypoxia inducible factor-1α (HIF-1α). The functional relationship between hKOR and HIF-1α was investigated using RT-PCR, Western blot, luciferase reporter, mutagenesis, siRNA and receptor-ligand binding assays. In surviving neurons, DFO increased HIF-1α expression and its amount in the nucleus. DFO also dramatically increased hKOR expression. Two (designated as HIFC and D) out of four potential HIF response elements of the hKOR gene (HIFA–D) synergistically mediated the DFO response. Mutation of both elements completely abolished the DFO-induced effect. The CD11 plasmid (containing HIFC and D with an 11 bp spacing) produced greater augmentation than that of the CD17 plasmid (HIFC and D with a 17 bp-spacing), suggesting that a proper topological interaction of these elements synergistically enhanced the promoter activity. HIF-1α siRNA knocked down the increase of endogenous HIF-1α messages and diminished the DFO-induced increase of hKOR expression. Increased hKOR expression resulted in the up-regulation of hKOR protein. In conclusion, the adaptation of neuronal hKOR under hypoxia was governed by HIF-1, revealing a new mechanism of hKOR regulation. PMID:28117678
Marquez-Nostra, Bernadette V.; Lee, Supum; Laforest, Richard; Vitale, Laura; Nie, Xingyu; Hyrc, Krzysztof; Keler, Tibor; Hawthorne, Thomas; Hoog, Jeremy; Li, Shunqiang; Dehdashti, Farrokh; Ma, Cynthia X.; Lapi, Suzanne E.
High levels of expression of glycoprotein non-metastatic B (gpNMB) in triple negative breast cancer (TNBC) and its association with metastasis and recurrence make it an attractive target for therapy with the antibody drug conjugate, glembatumumab vedotin (CDX-011). This report describes the development of a companion PET-based diagnostic imaging agent using 89Zr-labeled glembatumumab ([89Zr]DFO-CR011) to potentially aid in the selection of patients most likely to respond to targeted treatment with CDX-011. [89Zr]DFO-CR011 was characterized for its pharmacologic properties in TNBC cell lines. Preclinical studies determined that [89Zr]DFO-CR011 binds specifically to gpNMB with high affinity (Kd = 25 ± 5 nM), immunoreactivity of 2.2-fold less than the native CR011, and its cellular uptake correlates with gpNMB expression (r = 0.95). In PET studies at the optimal imaging timepoint of 7 days p.i., the [89Zr]DFO-CR011 tumor uptake in gpNMB-expressing MDA-MB-468 xenografts had a mean SUV of 2.9, while significantly lower in gpNMB-negative MDA-MB-231 tumors with a mean SUV of 1.9. [89Zr]DFO-CR011 was also evaluated in patient-derived xenograft models of TNBC, where tumor uptake in vivo had a positive correlation with total gpNMB protein expression via ELISA (r = 0.79), despite the heterogeneity of gpNMB expression within the same group of PDX mice. Lastly, the radiation dosimetry calculated from biodistribution studies in MDA-MB-468 xenografts determined the effective dose for human use would be 0.54 mSv/MBq. Overall, these studies demonstrate that [89Zr]DFO-CR011 is a potential companion diagnostic imaging agent for CDX-011 which targets gpNMB, an emerging biomarker for TNBC. PMID:29262642
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.
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. Copyright © 2014 Elsevier B.V. All rights reserved.
Mission Control Activities during the STS-3 Mission, Day-4 with: Maj. Gen. James A. Abrahamson, Associate Administrator of the Space Transportation System (STS), NASA Hdqs., conversing with Dr. Kraft; Glynn S. Lunney, Manager, Space Shuttle Program Office, JSC, Aaron Cohen, Manager, Space Shuttle Orbiter Project Office; and, J. E. Conner, Ford Aerospace Engineer at the Instrumentation and Communications Officer (INCO) Console position. 1. Glynn S. Lunney 2. Major General James A. Abrahamson 3. Aaron Cohen 4. J. E. Conner 5. Dr. Christopher Kraft JSC, Houston, TX
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Ricci, Lucia; Scatena, Alessia; Tacconi, Danilo; Ventoruzzo, Giorgio; Liistro, Francesco; Bolognese, Leonardo; Monami, Matteo; Mannucci, Edoardo
Mortality in patients with type 2 diabetes and diabetic foot osteomyelitis (DFO) have been explored in few small studies with a short follow-up. Aim of the present study is to assess all-cause and cardiovascular mortality and predictors of mortality in a consecutive series of patients with DFO. Patients with a diagnosis of DFO, attending the Diabetic Foot Unit of San Donato Hospital in Arezzo between January 1st, 2012 and December 31st, 2013, were included in this retrospective study. Information on all-cause mortality up to December 1st, 2016, was obtained from the registry of the Local Health Unit of Arezzo, which contains updated records of all persons living in Tuscany. One hundred ninety-four patients were included in the study. During a mean period of observation of 2.8±1.4years, 73 (37.6%) died, with a yearly rate of 13.2%. Of the 73 deaths, 59 were attributable to cardiovascular causes. After adjusting for possible confounders in a Cox analysis, site of osteomyelitis (hindfoot vs mid/forefoot) was associated with a higher mortality, and surgical treatment with a lower mortality. Mortality in patients with DFO appears to be much higher than that reported in clinical series of patients with diabetic foot ulcers, particularly when hindfoot is affected. Copyright © 2017. Published by Elsevier B.V.
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.
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
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Haleagrahara, Nagaraja; Siew, Cheng Jun; Ponnusamy, Kumar
The catecholaminergic neurotoxin 6-hydroxydopamine is used to lesion dopaminergic pathways in the experimental animal models of Parkinson's disease. The present study was aimed to evaluate the combined treatment with bioflavonoid quercetin (QN) and desferrioxamine (DFO) on 6-hydroxydopamine (6-OHDA) - induced neurotoxicity in the striatum of rats. Adult, male Sprague - Dawley rats were divided into control, sham lesion, 6-OHDA treated (300 µg, intracisternal), 6-OHDA with QN (50 mg/kg) treated, 6-OHDA with DFO (50 mg/kg) treated and 6-OHDA with QN and DFO treated groups. Striatal dopamine, protein carbonyl content (PCC), glutathione (GSH) and superoxide dismutase (SOD) were estimated. There was a significant increase (p < 0.05) in PCC and decrease in dopamine, GSH and SOD level and striatal neuronal number with 6-OHDA treatment. QN and DFO treatment significantly (p < 0.05) reduced these changes showing a significant neuronal protection. Combined treatment has a more significant effect (p < 0.05) in protecting the neurons and increasing the antioxidant enzymes in the striatum. In conclusion, an antioxidant with iron chelator treatment showed a significant neuroprotective effect against 6-hydroxydopamine (6-OHDA) by preventing dopaminergic neuronal loss and maintaining the striatal dopamine level.
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Pool, Sam L.
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.
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... 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 may...
... 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 Coast...
Mladĕnka, Premysl; Kalinowski, Danuta S; Haskova, Pavlína; Bobrovová, Zuzana; Hrdina, Radomír; Simůnek, Tomás; Nachtigal, Petr; Semecký, Vladimĺr; Vávrová, Jaroslava; Holeckova, Magdaléna; Palicka, Vladimir; Mazurová, Yvona; Jansson, Patric J; Richardson, Des R
Iron (Fe) chelators are used clinically for the treatment of Fe overload disease. Iron also plays a role in the pathology of many other conditions, and these potentially include the cardiotoxicity induced by catecholamines such as isoprenaline (ISO). The current study examined the potential of Fe chelators to prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO contains the classical catechol moiety that binds Fe and may form redox-active and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line, H9c2, which was treated with ISO in the presence or absence of the chelator, desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more effective than DFO, with the latter showing activity only at a high, clinically unachievable concentration. Further studies in vitro showed that interaction of ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting that this mechanism was not involved. Studies in vivo were initiated using rats pretreated intravenously with DFO or PCTH before subcutaneous administration of ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented catecholamine-induced mortality and reduced cardiotoxicity. This study demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo, demonstrating that Fe plays a role, in part, in the pathology observed.
Berdejo, Stephanie; Rowe, Mark; Bond, John W
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. © 2011 American Academy of Forensic Sciences.
... ENVIRONMENTAL PROTECTION AGENCY [FRL-9106-8] Science Advisory Board Staff Office; Notification of.... SUMMARY: The Environmental Protection Agency (EPA or Agency) Science Advisory Board (SAB) Staff Office is... may contact Ms. Kyndall Barry, Designated Federal Officer (DFO), EPA Science Advisory Board (1400F), U...
... ENVIRONMENTAL PROTECTION AGENCY [FRL-9124-1] Science Advisory Board Staff Office; Notification of... Environmental Protection Agency (EPA) Science Advisory Board (SAB) Staff Office announces a public meeting of... may contact Ms. Kyndall Barry, Designated Federal Officer (DFO), EPA Science Advisory Board (1400F), U...
Drager, Justin; Ramirez-GarciaLuna, Jose Luis; Kumar, Abhishek; Gbureck, Uwe; Harvey, Edward J; Barralet, Jake E
Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 μL (200 μM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm 2 vs. 33.2 mm 2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of
Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.
Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism
... pursuant to IEEPA: 1. GOLDEN AARON PTE. LTD. 2. MAX MYANMAR GROUP OF COMPANIES 3. DAGON INTERNATIONAL... AVENIR EXECUTIVE SERVICED APARTMENT 9. MAX (MYANMAR) CONSTRUCTION CO. LTD. 10. MAX MYANMAR GEMS AND JEWELLERY CO. LTD. 11. MAX MYANMAR MANUFACTURING CO. LTD. 12. MAX MYANMAR SERVICES CO. LTD. 13. MAX MYANMAR...
..., 2010, 8:30 a.m. to 4 p.m., Salem, OR. ADDRESSES: Salem District Office, 1717 Fabry Road SE., Salem, OR... members may be obtained from Richard Hatfield, BLM Salem District Designated Official, 1717 Fabry Road..., forest ecosystems, and infrastructure. Aaron G. Horton, District Manager. [FR Doc. 2010-13293 Filed 6-2...
MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL COMMUNITIES THESIS Aaron L... MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL COMMUNITIES THESIS Presented to the Faculty Department of Systems Engineering and...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED AFIT/GCA/ENV/08-D01 MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL
American Educational Research Association, Washington, DC.
Three of the papers in this collection present the separate models--school based, employer based, and home-community based. Titles of the five papers are: (1) "Facts and Fantasies of Career Education" by Gorden I. Swanson, (2) "Strategies for Implementing Career Education: A School Based Model" by Aaron J. Miller, (3)…
... of NGA police officer candidates. Affected Public: Individuals or Households. Annual Burden Hours.... Frequency: On occasion. Respondents are applicants who are applying for NGA police officer positions. NGA... fill the position of NGA police. Dated: December 11, 2013. Aaron Siegel, Alternate OSD Federal Register...
Couzens, Lindsay Starr
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…
Foster, Andrea L.
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…
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…
... Time for Filing Requests for Reevaluation. FOR FURTHER INFORMATION CONTACT: Aaron Szabo, Financial Analyst, Financial Analysis and International Projects Branch, Division of Policy and Rulemaking, Office... Analysis and Recommendation In reaching this conclusion, the NRC staff considered the structure of the...
... DEPARTMENT OF DEFENSE Department of the Navy [Docket ID USN-2012-0007] Privacy Act of 1974; System of Records AGENCY: Department of the Navy, DoD. ACTION: Notice to Alter a System of Records. SUMMARY...). Dated: May 8, 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense...
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DOD-2012-OS-0055] Privacy Act of 1974..., 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. HDTRA 010... Reconstruction for the purposes of reviewing and overseeing the Department of Defense Radiation Dose...
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DoD-2013-OS-0005] Privacy Act of 1974...: January 23, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. V1... Information Act Program; and DoD [[Page 5789
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID DOD-2011-OS-0118] Privacy Act of 1974; System of Records AGENCY: Office of the Secretary, Department of Defense (DoD). ACTION: Notice to Amend a.... Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. DWHS E05 System...
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DOD-2012-OS-0062] Privacy Act of 1974; System of Records AGENCY: Defense Information Systems Agency, DoD. ACTION: Notice to alter a system of..., 2012. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. K890.01...
NASA employees Anita Douglas (l to r), Amy Grose, Aaron Brooks and Cabrina Bell sort through early contributions to the 2011 Feds Feed Families Food Drive at Stennis Space Center. Each summer for three years, federal agencies across the nation have worked together to collect nonperishable food for local food banks across the country.
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DOD-2011-OS-0064] Privacy Act of 1974..., 2011. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. DHRA 06.... SUMMARY: The Office of the Secretary of Defense proposes to alter a system of records in its inventory of...
Astronomy Professor of Earth & Planetary Science imke at berkeley dot edu (510) 642.1947 Stanley Klein UC Irvine Aaron Barth Associate Professor Physics and Astronomy barth at uci dot edu (949) 824.3013 dot edu (310) 206.7853 Andrea Ghez Professor of Astronomy ghez at astro dot ucla dot edu (310
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…
Hodapp, Albert Fed
Aaron (2005) described the "family as the nation's smallest school" and "the home as the first school." Furthermore, studies document that 90% of the differences in academic achievement can be explained by five factors: (a) two-parent households; (b) school absenteeism; (c) amount read for homework; (d) quality and quantity of…
Lierheimer, Kristin; Stichter, Janine
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,…
.... Berkheimer (PA) Michael D. DeBerry (WV) Tony K. Ellis (IN) Jerry L. Gibson (FL) Rici W. Giesseman (OH) George.... McClain (MI) Daniel E. Miller (VA) Buddy W. Myrick (TX) James L. Okonek (WI) Aaron L. Paustian (IA) John J. Pribanic (TX) Alan J. Reynaldos (NJ) Charles L. Rill, Sr. (MD) John P. Rodrigues (TX) Robert Smiley (NM...
... S. Johannsen (IA) Charles E. Johnston (MO) Harry L. Jones (OH) Mearl C. Kennedy (OH) Aaron C...) Bobby G. Minton (NC) Charles J. Morman (FL) Larry A. Nienhuis (MI) Corey L. Paraf (IL) Ronald M. Price (MD) John P. Raftis (FL) Scott D. Russell (WI) Alton M. Rutherford (FL) Charles L. Schnell (FL) Andrew...
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…
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…
... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID DOD-2011-HA-0033] Submission for OMB Review; Comment Request ACTION: Notice. The Department of Defense has submitted to OMB for clearance, the.... Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. [FR Doc. 2011-33476...
to Muscular Exercise. Epidemiology. Behavior change. and Intervention in Chronic Lung Disease. (L. Hall and G. Meyer, editors), Human Kinetics Publ...Aaron. Feedback and Feed-Forward Mechanisms. Future Directions in Exercise and Sport Science Research. (J.S. Skinner, et al., eds). Human Kinetics Books
Chronic Lung Disease. (L. Hall and G. Meyer, eds) Human Kinetics Publ., Champaign, IL pp 199-223, 1988. 3) Dempsey, J.A., E. Aaron and K. Henke...and Sports Science Research. (J.S. Skinner, et al., eds) Human Kinetics Books, Champaign, IL. pp 313-327, 1989. 8) Powers, S.K., J. Lawler, J.A
..., 9800 Savage Road, Suite 6848, Fort George G. Meade, MD 20755-6848. FOR FURTHER INFORMATION CONTACT: Marian T. Roche, Director, Technology Transfer Program, 9800 Savage Road, Suite 6848, Fort George G. Meade, MD 20755-6848, telephone (443) 634-3514. Dated: April 24, 2013. Aaron Siegel, Alternate OSD...
De Costa, Peter I.; Tigchelaar, Magda; Cui, Yaqiong
Following Sayer's (2010) examination of reflexivity and habitus, we focus on the "transnational habitus" (Darvin & Norton 2015) of Aaron, a Chinese international student at a U.S. university. Specifically, we examine how he wrestled with being identified as an ESL learner despite having attended a U.S. high school. Also exploring the…
Amorphous carbon nanosphere used as the anode material for Li-intercalation in Lithium-ion energy storage. This structure was obtained through a thermal annealing process at a temperature of 3000 degree Kelvin, simulated using the LAMMPS molecular dynamics code on the LCRC Fusion resource. Science: Kah Chun Lau and Larry Curtiss Visualization: Aaron Knoll, Mark Hereld and Michael E. Papka
... contact Aaron Wingad at the Office of Rural Health Policy (ORHP) via Telephone at (301) 443-0835 or by e... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration National Advisory Committee on Rural Health and Human Services; Notice of Meeting In accordance with section 10(a)(2...
Aaron Koh contributed to a collection of multi-site global ethnographic articles published here (2014, Vol. 12, No. 2) that present class reproduction as operationalised in elite education. While the collection adds to the current international critique of meritocracy, a close look at Koh's contribution reveals that critical ethnography can lose…
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…
... on them. The Task Force has until the end of 2013 to complete the report but it is hoped that the... computing technology industry itself. Mr. Aaron Berstein then volunteered to contact Microsoft to inquire into the possibility of Microsoft providing an online collaborative space software tool for use...
... exemption from the prohibition against persons with insulin-treated diabetes mellitus (ITDM) operating... diabetes using insulin, and is able to drive a Commercial Motor Vehicle (CMV) safely. Mr. Aaron meets the... management and monitoring, has stable control of his diabetes using insulin, and is able to drive a CMV...
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…
Sibatov, R. T.; Svetukhin, V. V.
Based on fractional differential generalizations of the Ham and Aaron-Kotler precipitation models, we study the kinetics of subdiffusion-limited growth and dissolution of new-phase precipitates. We obtain the time dependence of the number of impurities and dimensions of new-phase precipitates. The solutions agree with the Monte Carlo simulation results.
Nebesniak, Amy L.; Burgoa, A. Aaron
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…
Yates, Eleanor Lee
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…
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…
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…
...- feet in capacity), near Fort Collins, Colorado; (2) the proposed T- Cross Reservoir (25,000 acre-feet.... Applicant Contact: Aaron Million, Wyco Power and Water, Inc., 1436 West Oak, Fort Collins, CO 80521, phone (970) 215-2603. FERC Contact: Jim Fargo; phone: (202) 502-6095. Deadline for filing comments, motions...
Fulfillment of the Requirements for the Degree of Master of Science in Financial Analysis Aaron M. Lemke, BS Captain, USAF March 2010... ACCA ), provides substantial support for the impact of part size on life cycle cost for payload aircraft. This research evaluates select methods used...1: Boeing 787 External Skin Materials (Boeing, 2010) ..........................................9 Figure 2: ACCA Task Sequence (Neumeier et al, 2009
.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy... transmittal, policy justification, and Sensitivity of Technology. Dated: November 19, 2012. Aaron Siegel... of logistics and program support. (iv) Military Department: Army (UKB) [[Page 70155
... is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy... transmittal, policy justification, and Sensitivity of Technology. Dated: May 22, 2012. Aaron Siegel, Alternate...
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…
Jenson, Jeffrey M.
Recent advances in the field of prevention have led to a deeper understanding of the causes of adolescent problem behavior and to the identification of efficacious strategies to prevent delinquency, drug use, and other antisocial conduct. This 2009 Aaron Rosen lecture to members of the "Society for Social Work and Research" traces the evolution of…
5 Aaron Terrazak, “Mexican Immigrants in the United States,” February 2010, linked from Migration Policy Institute Home Page at Migration ...Sentenced For Conspiracy That Supplied Weapons to Sinaloa Cartel, Ambassador Pascual Congratulates Mexico for Arrest of Edger Valdes Villarreal,” United
... transmittal, policy justification, and Sensitivity of Technology. Dated: December 18, 2012. Aaron Siegel... Processor Cabinets, 2 Video Wall Screen and Projector Systems, 46 Flat Panel Displays, and 2 Distributed Video Systems), 2 ship sets AN/SPQ-15 Digital Video Distribution Systems, 2 ship sets Operational...
Schutz, Aaron; Sandy, Marie G.
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,…
McCuaig, Louise; Quennerstedt, Mikael
Sport, health and physical education (SHPE) researchers have increasingly embraced the salutogenic model of health devised by Aaron Antonvosky, to re-understand and problematise the relation between movement, physical activity or physical education on one hand, and health on the other. However, contemporary research employing Antonovsky's theories…
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…
.... 20120358, Draft Supplement, BOEM, 00, Gulf of Mexico Outer Continental Shelf (OCS) Oil and Gas Lease Sales...: Aaron O. Allen 805-585-2148. EIS No. 20120360, Final EIS, BLM, 00, PROGRAMMATIC--Allocation of Oil Shale and Tar Sands Resources on Lands Administered, Propose to Amend 10 Land Use Plans in Colorado, Utah...
of vehicle types, including conventional vehicles, electric-drive vehicles, and fuel cell vehicles types," said NREL Senior Engineer Aaron Brooker. FASTSim facilitates large-scale evaluation of and on-road performance. Learn more about NREL's sustainable transportation research.
Cook, Erika; Becker, Aaron
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…
... HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program... Continued HIV Primary Medical Care. SUMMARY: To prevent a lapse in comprehensive primary care services for persons living with HIV/AIDS, HRSA will provide one-time noncompetitive Part C funds to the Aaron E. Henry...
... DEPARTMENT OF DEFENSE Department of the Army [Docket ID: USA-2013-0015] Privacy Act of 1974.... Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. A0190-47 DAPM-ACC..., classification, progress reports, victim/witness' full name, address and telephone number, victim impact...
... DEPARTMENT OF DEFENSE Department of the Navy [Docket ID USN-2013-0018] Privacy Act of 1974; System... 10, 2013. Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. N06110... of Social Security Number (SSN), Department of Defense Identification Number (DoD ID Number), Unit...
... DEPARTMENT OF DEFENSE Department of the Air Force [Docket ID: USAF-2013-0005] Privacy Act of 1974; System of Records AGENCY: Department of the Air Force, DoD. ACTION: Notice to alter a System of Records.... Aaron Siegel, Alternate OSD Federal Register Liaison Officer, Department of Defense. F036 AF PC U System...
Melas, Christos D.; Zampetakis, Leonidas A.; Dimopoulou, Anastasia; Moustakis, Vassilis
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,…
NREL project manager Aaron Bloom introduces NREL’s Eastern Renewable Generation Integration Study (ERGIS) and high-performance computing capabilities and new methodologies that allowed NREL to model operations of the Eastern Interconnection at unprecedented fidelity. ERGIS shows that the Eastern Interconnection can balance the variability and uncertainty of wind and solar photovoltaics at a 5-minute level, for one simulated year.
.... Martinez, 47, has had macular scarring and retinal detachment in his right eye due to a traumatic injury.... Aaron L. Paustian Mr. Paustian, 42, has macular scarring in his right eye due to a traumatic injury... in a CMV. Kenneth R. Riener Mr. Riener, 48, has a prosthetic right eye due to a traumatic injury...
Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M
Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sooriyaarachchi, Melani; Gailer, Jürgen
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.
D'Elia, Valentina; Materazzi, Stefano; Iuliano, Gianpaolo; Niola, Luca
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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Hackley, P.C.; Peper, J.D.; Burton, W.C.; Horton, J. Wright
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
Oteo, M.; Romero, E.; Cámara, J. A.; de Martino, A.; Arroyo, A. G.; Morcillo, M. Á.; Squatrito, M.; Martinez-Torrecuadrada, J. L.; Mulero, F.
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
Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.
McLeod, C; Fleeman, N; Kirkham, J; Bagust, A; Boland, A; Chu, P; Dickson, R; Dundar, Y; Greenhalgh, J; Modell, B; Olujohungbe, A; Telfer, P; Walley, T
To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with chronic anaemia such as beta-thalassaemia major (beta-TM) and sickle cell disease (SCD). Electronic databases were searched up to March 2007. Methods followed accepted procedures for conducting and reporting systematic reviews and economic evaluations. A total of 14 randomised controlled trials (RCTs) involving a study population of 1480 (ranging from 13 to 586) met the inclusion criteria. There was a high degree of heterogeneity between trials in terms of trial design and outcome reporting. As such it was only possible to meta-analyse serum ferritin data from six trials making comparisons between deferiprone and DFO and combination therapy and DFO. Only one of the results was statistically significant, favouring combination therapy over DFO alone for serum ferritin at 12 months. How this translates into iron loading in organs such as the heart is unclear, nor was it possible to determine the long-term benefits of chelation therapy. Eight full economic evaluations (one full paper; seven abstracts) were included in the review. The results were generally consistent and appear to demonstrate the cost-effectiveness of deferasirox compared with DFO for the treatment of iron overload in a number of different patient populations and study locations. However, a number of assumptions and, in the case of the long-term studies, extrapolation from short-term RCT data were required, which render the results highly speculative at best. Because of the paucity of long-term data we developed a simple, short-term (1 year) model to assess the costs and benefits of deferasirox, deferiprone and DFO in patients with beta-TM and SCD from an NHS perspective. A number of assumptions were required to generate results and, as such, they should be interpreted as indicative rather than factual. Our model suggests that
Senneville, Eric; Nguyen, Sophie
Both medical and surgical approaches have been shown to be effective in the treatment of patients with diabetic foot osteomyelitis (DFO). In patients with risk factors of bad outcome such as major bone destruction, concomitant acute infections requiring drainage, problems in limb perfusion, highly resistant bacteria, and contraindication for or patient refusal of prolonged antibiotic therapy, the choice of surgery does not require further discussion. On the contrary, modest changes of bone on imaging assessment and no limiting factors as described above make medical treatment an attractive option for patients with DFO provided the rules of antibiotic treatment of chronic osteomyelitis are respected. The key question may not be to oppose surgery and medical treatment but to identify patients who need surgery and those who do not. There is currently no classification or score system that may allow physician to decide whether medical or surgical approach is best adapted to a given patient, and so both experience and skill of the multidisciplinary team appear paramount for guiding the choice of the best adapted ("tailored") strategy in a given patient. In this regard, it would be interesting to compare surgical and medical approaches for DFO that apparently may benefit from one or another (ie, bone lesions seen on plain radiographs of the foot but without bone fragmentation or multiple sites of osteomyelitis, no contraindication to prolonged antibiotic therapy, and location of bone involvement that may allow conservative surgery). Given the current available data on the therapeutic options of DFO, it appears that surgery for those patients is obviously not an old-fashioned option. © The Author(s) 2014.
Aragón-Sánchez, Javier; Lipsky, Benjamin A; Lázaro-Martínez, Jose L
Osteomyelitis frequently complicates infections in the feet of patients with diabetes. Gram-positive cocci, especially Staphylococcus aureus, are the most commonly isolated pathogens, but gram-negative bacteria also cause some cases of diabetic foot osteomyelitis (DFO). These gram-negatives require different antibiotic regimens than those commonly directed at gram-positives. There are, however, few data on factors related to their presence and how they influence the clinical picture. We conducted a retrospective study to determine the variables associated with the isolation of gram-negative bacteria from bone samples in cases of DFO and the clinical presentation of these infections. Among 341 cases of DFO, 150 had a gram-negative isolate (alone or combined with a gram-positive isolate) comprising 44.0% of all patients and 50.8% of those with a positive bone culture. Compared with gram-positive infections, wounds with gram-negative organisms more often had a fetid odor, necrotic tissue, signs of soft tissue infection accompanying osteomyelitis, and clinically severe infection. By multivariate analysis, the predictive variables related to an increased likelihood of isolating gram-negatives from bone samples were glycated hemoglobin <7% (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.1-3.5) and a wound caused by traumatic injury (OR = 2.0, 95% CI = 1.0-3.9). Overall, patients whose bone samples contained gram-negatives had a statistically significantly higher prevalence of leukocytosis and higher white blood cell counts than those without gram-negatives. In conclusion, gram-negative organisms were isolated in nearly half of our cases of DFO and were associated with more severe infections, higher white blood cell counts, lower glycated hemoglobin levels, and wounds of traumatic etiology.
Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.
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.
... CONTACT: Master Chief Steven A. Hady, Designated Federal Officer, MLDC, at (703) 602-0838, 1851 South Bell....m.), August 24 (from 8 a.m. to 6:15 p.m.), and August 25, 2010 (from 8 a.m. to 4:45 p.m.). The.... National Guard and Reserve Briefings. August 24, 2010 8 a.m.-8:15 a.m. DFO opens the meeting. Commission...
REFERENCES Aubrey FT, Thomas JA, Kastelein RA (1988) Low-frequency underwater hearing sensitivity in belugas, Delphinapterus leucas . J Acoust Soc...J Acoust Soc Am 116:2504 DFO (2012) Recovery strategy for the beluga whale ( Delphinapterus leucas ) St. Lawrence estuary population in Canada...possible aminoglycoside-induced hearing loss in belugas ( Delphinapterus leucas ). J Acoust Soc Am 117:3936–3943 Klishin VO, Popov VV, Supin AY
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.
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
Siriwardana, Gamini; Seligman, Paul A
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
Siriwardana, Gamini; Seligman, Paul A
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. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Lei, Wenjia; Fan, Miao; Wang, Meilian; Wang, Yu; Sun, Wei; Sun, Xue; Zhang, Ying
Foramen ovale (FO) valve with a shape or motion abnormality is frequently detected during routine obstetric ultrasonic examinations. However, the hemodynamics mechanism of this entity remains unclear. The purpose of the study is to determine the relevance of interatrial communication restriction and resultant morphological modifications. We reviewed the echocardiographic records of fetuses with isolated abnormal FO valve evaluated between January of 2010 and december of 2016. The size (DFO) of the FO orifice, opening angle (α) of the FO valve, and dimensions of cardiac chambers, FO channel outlet (DOUT) and inferior vena cava (DIVC) were measured. We evaluated their (DFO, DOUT, α) relationships to the diameters of RA and DIVC. Five hundred and seventy normal fetuses were selected to establish the normal range of the DOUT/DIVC ratio so as to provide a criterion for restriction. An abnormal FO valve was identified in 89 fetuses without congenital heart disease, with restriction noted in 62 fetuses (45 fetuses with RA dilatation, 12 fetuses with RA and RV dilatation, and 5 fetuses with no RA dilatation). There were no significant correlations between RA/LA and DFO/DIVC, RA/ LA and α. RA/LA was negatively correlated with DOUT/DIVC (R2=0.97, p<0.01). For a fetus with an abnormal FO valve, right heart dilatation could be considered as an indicator of interatrial communication restriction, which could be assessed by evaluating the FO channel outlet. The degree of right atrium dilatation indicates the severity of the restriction.
Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong
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.
Huayhuaz, Jesus Antonio Alvarado; Vitorino, Hector Aguilar; Campos, Othon Souto; Serrano, Silvia Helena Pires; Kaneko, Telma Mary; Espósito, Breno Pannia
Iron acquisition by bacteria and fungi involves in several cases the promiscuous usage of siderophores. Thus, antibiotic resistance from these microorganisms can be circumvented through a strategy of loading toxic metals into siderophores (Trojan Horse Effect). Desferrioxamine (dfo) and its cell-permeant derivative desferrioxamine-caffeine (dfcaf) were complexed with aluminum or gallium for this purpose. The complexes Me(dfo) and Me(dfcaf) (Me=Al 3+ and Ga 3+ ) were synthesized and characterized by mass spectroscopy and cyclic voltammetry. Their relative stabilities were studied through competitive equilibria with fluorescent probes calcein, fluorescein-desferrioxamine and 8-hydroxyquinoline. Me(dfo) and Me(dfcaf) were consistently more toxic than free Me 3+ against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, demonstrating the Trojan Horse Effect. Wide spectrum antimicrobial action can be obtained by loading non-essential or toxic metal ions to microbes via a convenient siderophore carrier. Copyright © 2017 Elsevier GmbH. All rights reserved.
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
Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon
Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621
Rao, Allison J.; Erickson, Brandon J.; Cvetanovich, Gregory L.; Yanke, Adam B.; Bach, Bernard R.; Cole, Brian J.
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
relatively small contractural effort is to provide technical assistance to Dr. Frank Patten (DARPA) in evaluating data on materials, especially... Musikant , S. (ed.), Advances in Materials for Active Optics, Proceedings of SPIE, Volume 567, SPIE:Washington, 1985.  Lewis, Aaron, Del Priore...polysilane," J. Appl. Phys. 60 (1986) 3040-3044.  Hache, F., Ricard, D., Flytzanis, C., "Optical nonlinearities of small metal particles: surface
ii APPROVED: Col Drew W . Fallis Dean, Air Force Postgraduate Dental School iii Acknowledgements Special thanks to Col Howard Roberts, Maj...excerpts, is with the permission of the copyright owner. Signature AARON T. DANCB. MAJ. USAF, DC v Printed Name USAF Postgraduate Dental School Keesler...internal amalgam-dentin 3 interface. Preparations were accomplished by one operator using a high speed electric dental hand piece (EA-SlLT, Adee
worshiping a cow that one of them had made. Moses rebuked his brother and fought with him because he had not prevented this regression. According to the...narrative in the chapter entitled, "Taha," verse 94, Aaron informed Moses that he did not want to prevent the regression so he would not divide...from basic problems, an opposition beset by crisis and political forces among the Egyptian men in the street who are prevented from legitimate
Encoder-Decoder Architecture for Image Segmentation .” Cornell University Library. Computing Research Repository (CoRR). abs/1511.00561. 2. Anthony J. Bell...Aaron C Courville, and Pascal Vincent. 2012. “Unsupervised Feature Learning and Deep Learning : A Review and New Perspectives.” Cornell University...Linux Journal 122(June):1–4. 5. Francois Chollet. 2015.“Keras: Deep Learning Library for TensorFlow and Theano.” Available online at https://github.com
Press, 2010), Kindle edition. 35 Peter H. Diamandis and Steven Kotler , Abundance: The Future Is Better than You Think (New York: Free Press, 2012...Diamandis and Kotler , Abundance: The Future Is Better Than You Think, 6. 116 Maeve Duggan and Aaron Smith, “Social Media Update 2013,” Pew Research Center...Committee on Homeland Security and Governmental Affairs of the U.S. Senate). 298 Philip J. Palin, “Perspectives on Preparedness: Nudging Us Forward a
Ronald Green USMC Major General Philip Volpe, DO, MC USA Marjan Ghahramounlou Holloway, PhD Commander Aaron Werbel, PhD USN Table of Contents...and one civilian member serving as co-chairs for the group. Major General Philip Volpe, initially the Deputy Commander of Joint Task Force, National...and representation from each Service. Major General Philip Volpe was appointed as the military co-chair, and Ms. Bonnie Carroll was elected as the
The Challenge and the Promise: Strengthening the Force, Preventing Suicide and Saving Lives. Final Report of the Department of Defense Task Force on the Prevention of Suicide by Members of the Armed Forces
Sergeant Major Ronald Green USMC Major General Philip Volpe, DO, MC USA Marjan Ghahramounlou Holloway, PhD Commander Aaron...and one civilian member serving as co-chairs for the group. Major General Philip Volpe, initially the Deputy Commander of Joint Task Force, National...and representation from each Service. Major General Philip Volpe was appointed as the military co-chair, and Ms. Bonnie Carroll was elected as the
peacetime engagement, see General Charles Wald , “The Phase Zero Campaign,” Joint Force Quarterly, Issue 43, 4th Quarter 2006, available at http...with Principal Deputy Under Secretary Henry From the Pentagon,” February 7, 2007. 18 See, for example, Lisa Schirch and Aaron Kishbaugh, “Leveraging ‘3D...to the possibility of significant climate change.” Testimony of General Charles Wald , Member, Military Advisory Board, at a hearing on Climate
Phase Zero strategy and TSC, also known as peacetime engagement, see General Charles Wald , “The Phase Zero Campaign,” Joint Force Quarterly, Issue 43, 4th...16 DOD, “News Briefing with Principal Deputy Under Secretary Henry From the Pentagon,” February 7, 2007. 17 See, for example, Lisa Schirch and Aaron...Charles Wald , Member, Military Advisory Board, at a hearing on Climate Change and National Security Threats by the Senate Foreign Relations Committee on May
peacetime engagement, see General Charles Wald , “The Phase Zero Campaign,” Joint Force Quarterly, Issue 43, 4th Quarter 2006, available at http...USAID’s Office of U.S. Foreign 20 See, for example, Lisa Schirch and Aaron Kishbaugh...to the possibility of significant climate change.” Testimony of General Charles Wald , Member, Military Advisory Board, at a hearing on Climate
conflict. For more information on the Phase Zero strategy and TSC, also known as peacetime engagement, see General Charles Wald , “The Phase Zero...Principal Deputy Under Secretary Henry From the Pentagon,” February 7, 2007. 16 See, for example, Lisa Schirch and Aaron Kishbaugh, “Leveraging ‘3D...significant climate change.” Testimony of General Charles Wald , Member, Military Advisory Board, at a hearing on Climate Change and National Security
key leadership of critical R4 cost analysis. The second objective is to equip DoD planners with the framework for solving retrograde dilemmas in...informing key leadership of critical R4 cost analysis. The second objective is to equip DoD planners with the framework for solving retrograde...replicate the same dedication to individuals in similar situations in years to come. To Captains Aaron Burciaga, Mario Solano, and Maro Enoka, as well
CJCS’s) companion document, the Capstone Concept for Joint Operations (CCJO) (discussed below) "ibid., 28. "That said, it should be noted that it...Capstone Concept for Joint Operations (CCJO) The companion document to the JOE that answers the challenges of the future identified in the JOE (and...Karin E. Kitchens , Aaron Martin, A Review of the Army’s Modular Force Structure" (RAND National Defense Research Institute, Technical Report,Jun. 2011
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).
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).
SECURITY: WHY CRISES FAIL TO IMPACT ECONOMIC BEHAVIOR IN EAST ASIA by Aaron R. Sipos December 2017 Thesis Advisor: Michael Glosny Second...REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE ECONOMY OVER SECURITY: WHY CRISES FAIL TO IMPACT ECONOMIC BEHAVIOR IN EAST...release. Distribution is unlimited. 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) This study examines changes in economic behavior in
NREL project manager Aaron Bloom introduces NRELâs Eastern Renewable Generation Integration Study (ERGIS) and high-performance computing capabilities and new methodologies that allowed NREL to model operations of the Eastern Interconnection at unprecedented fidelity. ERGIS shows that the Eastern Interconnection can balance the variability and uncertainty of wind and solar photovoltaics at a 5-minute level, for one simulated year.
design . ERDC/CHL CHETN-X-2. Vicksburg, MS: U.S. Army Engineer Research and Development Center. http://chl.erdc.usace.army. mil/chetn REFERENCES...Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, edited by S. Solomon , D. Qin, M. Manning, Z. Chen, M...Duration- Frequency Curves for Infrastructure Design by Brian E. Skahill, Amir AghaKouchak, Linyin Cheng, Aaron Byrd, and Joseph Kanney
in the Land and Cyber Domains Lieutenant General Edward C. Cardon The U.S. Navy’s Evolving Cyber/ Cybersecurity Story Rear Admiral Nancy Norton...Olav Lysne Cyber Situational Awareness Maj. Gen. Earl D. Matthews, USAF, Ret Dr. Harold J. Arata III Mr. Brian L. Hale Is There a Cybersecurity ...Kallberg The Decision to Attack: Military and Intelligence Cyber Decision-Making by Dr. Aaron F. Brantly The Cyber Defense Review
Defense Actions Against Test-Set Attacks”, In Proceedings of the Conference on Artificial Intelligence (AAAI), San Francisco, CA, February, 2017...Scott Alfeld, Jerry Zhu and Paul Barford. “Data Poisoning Attacks against Autoregressive Models”, In Proceedings of the Conference on Artificial ... Intelligence (AAAI), Phoenix, AZ, February, 2016. 7) Aaron Cahn, Scot Alfeld, Paul Barford and S. Muthukrishnan. “An Empirical Study of Web Cookies
approaches to specific problems within the foreign affairs community ( e . g. , within DoD). The lag resulted from a variety of factors, in...ICATIOH / Prepared by: Herman M. Weil Airon Greenberg Larry German Douglas Hartwick Michael R. Leavitt Sponsored by: Defense Advanced...I Dr. G. Robert Franco, Project Director Dr. Herman M. Weil Mr. Aaron Greenberg Mr. Larry German Mr. Douglas Hartwick Dr. Michael
REPORT TYPE Master’s Thesis 3. DATES COVERED (From – To) 04 Sep 2011 - Mar 2013 4. TITLE AND SUBTITLE ELECTRONIC CHARACTERISTICS OF RARE EARTH ...ELECTRONIC CHARACTERISTICS OF RARE EARTH DOPED GaN SCHOTTKY DIODES THESIS Aaron B. Blanning...United States. AFIT-ENP-13-M-03 Electronic Characteristics of Rare Earth Doped GaN Schottky Diodes THESIS Presented to the Faculty
AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY THE FASTEST OODA LOOP : THE IMPLICATIONS OF BIG DATA FOR AIR POWER by Aaron J. Dove, Maj, USAF A...Use of Big Data Thus Far..............................................................16 The Big Data Boost To The OODA Loop ...processed with enough accuracy that it required minimal to no human or man-in-the loop vetting of the information through Command and Control (C2
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…
must not execute the targeted killing. • The targeted killing must not be conducted with “ poison , expanding bullets, or other prohibited weapons” under...responded with a never-ending string of poisonings , bombings, kidnappings, and shootings. Chechen militants continue to replace lost leaders. Over the...34 Aaron Mannes, “Testing the Snake Head Strategy: Does Killing or Capturing Its Leaders Reduce a Terrorist Group’s Activity?” Journal of
has been implicated as a salient player in the pathobiology of cancers of epithelial origin, e.g. prostate, cervix , ovarian, colon and...ANSI Std. Z39.18 W81XWH-10-1-0481 Heterobivalent Imaging Agents Targeting Prostate Cancer Training Aaron LeBeau University of California, San...Francisco San Francisco, CA 94103 Annual Summary 31 MAY 2010 - 1JUN 201101-06-2011 To determine the utility of imaging MT-SP1 in cancer , xenografts of
working jointly with NRL, performed a domain analysis ( Gabbard et al., 2002) to create a context for usability engineering effort, performed formative...rectangle to provide a background enabled the fastest user performance ( Gabbard et al., 2007). Tracking the user’s head position relative to the real...thank Yohan Baillot, Reinhold Behringer, Blaine Bell, Dennis Brown, Aaron Bryden, Enylton Coelho, Elliot Cooper-Balis, Deborah Hix, Joseph Gabbard
Roy Dickinson, Mr. John A. Kay, Mr. Benton Ross, and the staff of the Texas Highway Department District Headquarters of Wichita Falls for...of the earliest settlers in King County was Isom Lynn, who came there in 1877 with friends, John and Aaron Lasater, from Jack County. The Lasaters...J. W. Williams, "Some Northwest Texas Trails after Butterfield," West Texas Historical Association Year Book 42 (1966), pp. 78-79. 23. John R
developments within ACT, and building on the leadership and success of the outgoing U.S. commander, General James Mattis , U.S. Marine Corps (who retains...following the end of the war in Iraq. The author would like to thank RAND President James Thomson, who supported the development of a proj- ect plan designed...bers from diverse issue backgrounds, all of whom have extensive experience both in research and in policy formulation. These were David Aaron, James
PROCEEDINGS Spring 2016 Vol. 73, Number 1 Safety Management System Objectives 6 Safety Management Facilitates Safe Vessel Operation Vessel systems...crew, and operations. by LCDR Aaron W. Demo 9 Safety Management Systems to Prevent Pollution from Ships Standard procedures protect the environment...by LCDR Michael Lendvay 11 Dead Reckoning by Safety Management ? Check your course. by LCDR Corydon F. Heard IV Safety Management Systems and the Outer
assistance of Maj. Aaron Byerley were largely responsible for my decision to stay on. 4t Contents Abstract Acknowledgements Nomenclature Chapter 1...The use of shr sensitive liquid crystals in aerodynamic measurements has been a mor wPu imovation. Two different prcesses can be employed to...transition location. The steady-state heat transfer technique is unsuited for use on complex geometries, may be time consuming , and has an element of
among the people. —Mao Tse Tung, On Guerrilla Warfare2 In the summer of 1899, Lieutenant Matthew Batson was commanding L Troop, 4th U.S. Cavalry...Pershing, from the commander of the Constabulary, Brigadier General Henry Allen , to General Leonard Wood, all recognized that “ the successful leader...England unto Pharaoh, “You’ve had miracles before, When Aaron struck your rivers into blood; But if you watch the Sergeant, he can show you something
Energy for Wind Systems Today Cost and Value of Wind Power-Implications of Wind Turbine Design, JÃ¡nos Aaron Smith, PPI Session II: Uncertainty Impacts on Wind Turbine Design and Performance Mitigation of Wind Turbine Design Load Uncertainties, Anand Natarajan, DTU Wind Energy Uncertainty in the Wind
Powell. (2012). Dioxin exposure enhances nuclear localization of androgen receptor. The 8th Annual National Symposium on Prostate Cancer by CCRTD...cholesterol. Mol . Cellu. Endo. 295:115-120. 2. Siegel, R., Naishadham, D., and Jemal, A. (2012). Cancer Statistics, 2012. CA Cancer J Clin 62: 10-29...Ul DIOXIN J!1XPOSURE EN CES NUCLEAR LOCALIZATION OF ANDROGEN RECEPTOR\\~f..aTayia Aaron, nd Joann Powell, Center for Cancer Research and Therapeutic
this year’s work, contains natural bowhead whale calls recorded with a 12-element vertical array in the Arctic Ocean off the north coast of Alaska...This data set was collected and shared with this research project by Dr. Aaron Thode of Scripps Institution of Oceanography. The whale call frequencies...performance of STR and conventional mode filtering for ranging the recorded whale calls. Figure 1. Arctic ocean sound channel used for simulations of
based metal-oxide nano- hair structures for optical vortex generation," Opt. Express 23, 19056-19065 (2015) 15. Li, Yuan, Zeyu Zhang, Wenzhe Li, Jerome...Indumathi Raghu Srimathi, Aaron J. Pung, Yuan Li, Raymond C. Rumpf, and Eric G. Johnson, "Fabrication of metal-oxide nano- hairs for effective index...Grating Based Optical Nano- Hairs Using ALD Nano- Patterning Subwavelength gratings (SWGs) based artificial dielectric elements are used to obtain the
UNCLASSIFIED: Distribution Statement A. Approved for public release. DISCLAIMER: Reference herein to any specific commercial company , product...FunctionBay, S. Korea – NVIDIA – Caterpillar – MSC.Software – Advanced Micro Devices (AMD) 14-16 AUG 2012 Aaron Bartholomew Makarand Datar...16GB DDR2 Graphics: 4x NVIDIA Tesla C1060 Power supply 1: 1000W Power supply 2: 750W Assembled Quad GPU Machine 14-16 AUG 2012 30
Aaron Sloman (none of whom can be held responsible, of course, fcor the opinions expressed herein). Special thanks are also due to John Lyons for valuable...Meanings 12 7 Parametric Ambiguity 14 8 The Economic Necessity of Ambiguity 16 9 Semantic Interpretation 19 10 Semantics of the Internal Language 21 11...sufficiently low order organisms, the behavioral characteristics of that organism in response to stimuli are essentially "wired in" by their genes
Rosenwasser) Code RD-I Washington, D.C. 20360 Washington, D.C. 20380 Naval Civil Engineering Laboratory 1 Dean William Tolles Attn: Dr. R. W. Drisko...Ocean Systems Center 11 apel Street San Diego, California 92152 wton, Massachusetts 02158 Dr. J. J. Auborn Dr. Adam Heller Bell Laboratories Bell...University Research Triangle Park, NC 27709 Evanston, Illinois 60201 Dr. William Ayers Dr. Aaron Fletcher ECD Inc. Naval Weapons Center P.O. Box 5357 Code
A Cognitive Process Theory of Writing,” College Composition and Communication 32, no. 4 (December... Informative essay • Personal response to a text • Informative website • Literacy narrative posted to a blog • Critique of a text • Critique of...Fowler and Aaron: • Informative essay • Personal response to a text • Informative website • Literacy narrative posted to a blog • Critique of a
Society of America, (12 2012): 2643. doi: Christopher F. Neese, Ivan R. Medvedev, Grant M. Plummer, Aaron J. Frank, Christopher D. Ball, Frank C. De...NCNCS in view of quantum monodromy, Physical Chem Chem Physics, (02 2010): . doi: Ivan R. Medvedev, Christopher F. Neese, Grant M. Plummer, Frank C...Christopher F. Neese, Frank C. De Lucia, Ivan R. Medvedev, Bob D. Guenther . Terahertz Signature Modeling for Kill Assessment and Warhead Materials
Bhatia, Anand K. (Editor)
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.
Aaron Baker CONTRACTING ORGANIZATION: University of Texas at Austin Austin TX 78712 REPORT DATE: October 2017 TYPE OF REPORT : Annual PREPARED FOR...Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No
academies involving NSA cyber attacks on their net- works. This exercise afforded a realistic, intense cyber operation for our research team to...If so, please contact Capt Aaron Celaya at aa- firstname.lastname@example.org or 719-333-WERC. WERC Cognitive Neuroscience Lab Supports National... Neuroscience Lab – headed by Assistant Professors Chris D’Lau- ro, Ph.D. and LCDR Brian Johnson, Ph.D. – has taken the lead on researching concus
Ensuring the Trust of NAND Flash Memory: Going Beyond the Published Interface Austin H. Roach, Matthew J. Gadlage, James D. Ingalls, Aaron...reliability and trust of memories is very important, but because of incomplete documentation provided by commercial vendors and a lack of low-level...shown here that useful information about the trust and reliability of COTS NAND Flash components can be obtained by going beyond the standard product
The Winter 2000 edition of the OIT Times newsletter, a quarterly publication produced by the Office of Industrial Technologies, highlights the 1999 start-up projects, announces the OIT solicitation schedule for FY2000, and features the success of the Ohio diecasting showcase. One of the quarterly highlights was Secretary Richardson's presentation of a Certificate of Partnership to Malden Mills CEO Aaron Feuerstein at the dedication of the plant's new, advanced cogeneration system.
ER D C/ G SL T R- 14 -1 1 Field Evaluation of Ultra-High Pressure Water Systems for Runway Rubber Removal G eo te ch ni ca l a nd S tr...Field Evaluation of Ultra-High Pressure Water Systems for Runway Rubber Removal Aaron B. Pullen Applied Research Associates, Inc. 421 Oak Avenue...collaboration with Applied Research Associates, Inc. (ARA). Several types of commercial UHPW water blasting systems were tested on an ungrooved portland cement
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.
Fujita, S.; Parrenin, F.; Severi, M.; Motoyama, H.; Wolff, E. W.
Two deep ice cores, Dome Fuji (DF) and EPICA Dome C (EDC), drilled at remote dome summits in Antarctica, were volcanically synchronized to improve our understanding of their chronologies. Within the past 216 kyr, 1401 volcanic tie points have been identified. DFO2006 is the chronology for the DF core that strictly follows O2 / N2 age constraints with interpolation using an ice flow model. AICC2012 is the chronology for five cores, including the EDC core, and is characterized by glaciological approaches combining ice flow modelling with various age markers. A precise comparison between the two chronologies was performed. The age differences between them are within 2 kyr, except at Marine Isotope Stage (MIS) 5. DFO2006 gives ages older than AICC2012, with peak values of 4.5 and 3.1 kyr at MIS 5d and MIS 5b, respectively. Accordingly, the ratios of duration (AICC2012 / DFO2006) range between 1.4 at MIS 5e and 0.7 at MIS 5a. When making a comparison with accurately dated speleothem records, the age of DFO2006 agrees well at MIS 5d, while the age of AICC2012 agrees well at MIS 5b, supporting their accuracy at these stages. In addition, we found that glaciological approaches tend to give chronologies with younger ages and with longer durations than age markers suggest at MIS 5d-6. Therefore, we hypothesize that the causes of the DFO2006-AICC2012 age differences at MIS 5 are (i) overestimation in surface mass balance at around MIS 5d-6 in the glaciological approach and (ii) an error in one of the O2 / N2 age constraints by ~ 3 kyr at MIS 5b. Overall, we improved our knowledge of the timing and duration of climatic stages at MIS 5. This new understanding will be incorporated into the production of the next common age scale. Additionally, we found that the deuterium signals of ice, δDice, at DF tends to lead the one at EDC, with the DF lead being more pronounced during cold periods. The lead of DF is by +710 years (maximum) at MIS 5d, -230 years (minimum) at MIS 7a and +60
Hassan, Mohamed Abdel Malik; Tolba, Omar Atef
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
Hassan, Mohamed Abdel Malik; Tolba, Omar Atef
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. 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. 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). 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.
Recent studies have shown that diverse groups of bacteria adsorb metals to similar extents and uptake can be modeled using a universal adsorption model. In this study, XAFS has been used to resolve whether binding sites determined for single species systems are responsible for adsorption in more complex natural bacterial assemblages. Results obtained from a series of XAFS experiments on pure Gram positive and Gram negative bacterial strains and consortia of bacteria as a function of pH and Cd loading suggests that every bacterial strain has a complex physiology and they are all slightly different from each other. Nevertheless from the metal adsorption chemistry point of view, the main difference between them lies in the site ratio of three fundamental sites only - carboxyl, phosphoryl and sulfide. Two completely different consortia of bacteria (obtained from natural river water, and soil system with severe organic contamination) were successfully modeled in the pH range 3.4--7.8 using the EXAFS models developed for single species systems. Results thus obtained can potentially have very high impact on the modeling of the complex bacterial systems in realistic geological settings, leading to further refinement and development of robust remediation strategies for metal contamination at macroscopic level. In another study, solution speciation of Pb and Cd with DFO-B has been examined using a combination of techniques (ICP, TOC, thermodynamic modeling and XAFS). Results indicate that Pb does not complex with DFO-B at all until about pH 3.5, but forms a totally caged structure at pH 7.5. At intermediate pH conditions, mixture of species (one and two hydroxamate groups complexed) is formed. Cd on the other hand, does not complex until pH 5, forms intermediate complexes at pH 8 and is totally chelated at pH 9. Further studies were conducted for Pb sorption to mineral surface kaolinite with and without DFO-B. In the absence of DFO-B, results suggest outer sphere and inner
Holland, Jason P.; Sheh, Yiauchung; Lewis, Jason S.
Zirconium-89 is an attractive metallo-radionuclide for use in immunoPET due to the favorable decay characteristics. Standardized methods for the routine production and isolation of high purity and high specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52 ± 0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available 89Y-foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [89Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of 89Zr was found to be in the range 5.28 – 13.43 mCi/μg (470 – 1195 Ci/mmol) of zirconium. New methods for the facile production of [89Zr]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 [89Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal PET imaging studies have demonstrated that free 89Zr(IV) ions administered as [89Zr]Zr-chloride accumulate in the liver whilst [89Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immunoPET imaging of 89Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in both basic science and clinical investigations. PMID:19720285
Elalfy, M S; Aly, R H; Azzam, H; Aboelftouh, K; Shatla, R H; Tarif, M; Abdatty, M; Elsayed, R M
To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS). WISC in our study showed that 40% of cases were borderline mental function as regards total IQ. Neurophysiologic tests were significantly impaired in patients compared to control group, with significant impairment in those receiving desferrioxamine (DFO). P300 amplitude was significantly lower in cases compared to controls (2.24 and 4.66 uv, respectively), recording the shortest amplitude in patients receiving DFO. Altered metabolic markers in the brain were detected by MRS in the form of reduced N-acetylaspartate to creatine ratio in 78.3% of our cases. There were significant correlations between psychometric tests and both neurophysiologic (P300) and radiologic (MRS) tests. β-TM is associated with neurocognitive impairment that can be assessed by psychometric, neurophysiologic and radiologic tests. The role of hemosiderosis and iron chelation therapy on cognitive functioning still need more research. β-TM: beta thalassemia major; DFO: Dysferal; DFP: Deferiprone; DFX: Deferasirox; WISC: Wechsler Intelligence Scale for Children; VIQ: verbal IQ; PIQ: performance IQ; TIQ: total IQ; BVRT: Benton Visual Retention Test; WCST: Wisconsin Card Sort Test; MRS: Magnetic resonant spectroscopy; NAA/Cr ratio: N-acetylaspartate to creatine ratio.
Seibold, Uwe; Wängler, Björn; Wängler, Carmen
Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Kontoghiorghe, Christina N; Kontoghiorghes, George J
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.
Neu, Mary Patricia
The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pK as 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 a = 5.94, logβ 120 = 10.92; acetohydroxamic acid, pK a = 9.34, logβ 120 = 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-coordinatemore » 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 logβ 120 = 41.7. The solubility limited speciation of 242Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods.« less
Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert
Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.
Kettner, A. J.; Brakenridge, R.; van Praag, E.; Borrero, S.; Slayback, D. A.; Young, C.; Cohen, S.; Prades, L.; de Groeve, T.
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.
Fujii, Miki; Terashi, Hiroto; Yokono, Koichi
The aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32-1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C-reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C-reactive protein levels, long-term antibiotic therapy is recommended, and surgery should be planned after the C-reactive protein levels decrease, except in emergencies. © 2016 by the Wound Healing Society.
Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P
This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.
Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi
Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers' pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH(2)-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions.
Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi
Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers’ pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH2-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions. PMID:12397016
Stepaniak, Philip C.
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
Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L; Richard, John P
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.
Musallam, Khaled M; Taher, Ali T
Chronic transfusional iron overload leads to significant morbidity and mortality. While deferoxamine (DFO) is an effective iron chelator with over four decades of experience, it requires tedious subcutaneous infusions that reflect negatively on patient compliance. The novel oral iron chelators deferiprone (L1) and deferasirox (DFRA) opened new horizons for the management of transfusional siderosis. A large body of evidence is now available regarding their efficacy and safety in various populations and settings. Nevertheless, experience with both drugs witnessed some drawbacks, and the search for an ideal and cost-effective iron chelator continues.
Gulyaeva, T. L.; Arikan, F.; Stanislawska, I.
In addition to multi-scale spatio-temporal trends that shape the ionosphere variability, the ionosphere responds to the disturbances that are solar, geomagnetic and seismic in origin. In this study, post-seismic ionospheric disturbances are investigated retrospectively from 1999 to 2015 using two different sets of ionospheric maps of the F2 layer critical frequency, foF2. One set of foF2 maps is obtained by assimilating Global Ionospheric Maps (GIM) of Total Electron Content (TEC) into IRI-Plas model (IRI-Plas-foF2). Another set of hourly foF2 maps is obtained using PRIME-251 mapping technique (PRIME-foF2) by the assimilation of ionosonde foF2 data into IRI-CCIR model. The geomagnetic storms affecting the ionosphere are determined with relevant thresholds of geomagnetic AE, aa, ap, ap(τ) and Dst indices. It is observed that more than 60% of the earthquakes occur in the Equatorial Ionization Anomaly (EIA) region within the belt of geomagnetic latitudes ±40° N and geographic longitudes 90-190° E. The co-seismic foF2 disturbances, DfoF2, are identified for the cells of the map if an instant foF2 value is outside of pre-defined bounds of foF2 median (μ) and standard deviation (σ), μ ± 1σ, in the map fragment of 1000 km radius around the earthquake hypocenter. The results of positive ionospheric disturbances, DfoF2p, and negative disturbances, DfoF2n, in the EIA region during the 12 h after earthquake differ with respect to geomagnetic quiet and storm conditions, nighttime and daytime, magnitude and depth of the earthquake. The maximum spatial variability (for more than 50% of map cells in the vicinity of hypocenter) is observed with positive disturbances (DfoF2p) for the earthquakes that occurred during daytime at a depth of 70-300 km.
Butenko, Andrey; Kazinova, Olha; Kostromin, Sergey; Mikhaylov, Vladimir; Tuzikov, Alexey; Khodzhibagiyan, Hamlet
Generation of magnetic field in units of booster synchrotron for the NICA project is one of the most important conditions for getting the required parameters and qualitative accelerator operation. Research of linear and nonlinear dynamics of ion beam 197Au31+ in the booster have carried out with MADX program. Analytical estimation of magnetic field errors tolerance and numerical computation of dynamic aperture of booster DFO-magnetic lattice are presented. Closed orbit distortion with random errors of magnetic fields and errors in layout of booster units was evaluated.
Bentley, Anthony; Gillard, Samantha; Spino, Michael; Connelly, John; Tricta, Fernando
Patients with β-thalassaemia major experience chronic iron overload due to regular blood transfusions. Chronic iron overload can be treated using iron-chelating therapies such as desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) monotherapy, or DFO-DFP combination therapy. This study evaluated the relative cost effectiveness of these regimens over a 5-year timeframe from a UK National Health Service (NHS) perspective, including personal and social services. A Markov model was constructed to evaluate the cost effectiveness of the treatment regimens over 5 years. Based on published randomized controlled trial evidence, it was assumed that all four treatment regimens had a comparable effect on serum ferritin concentration (SFC) and liver iron concentration (LIC), and that DFP was more effective for reducing cardiac morbidity and mortality. Published utility scores for route of administration were used, with subcutaneously administered DFO assumed to incur a greater quality of life (QoL) burden than the oral chelators DFP and DFX. Healthcare resource use, drug costs (2010/2011 costs), and utilities associated with adverse events were also considered, with the effect of varying all parameters assessed in sensitivity analysis. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each treatment, with cost effectiveness expressed as incremental cost per QALY. Assumptions that DFP conferred no cardiac morbidity, mortality, or morbidity and mortality benefit were also explored in scenario analysis. DFP was the dominant strategy in all scenarios modelled, providing greater QALY gains at a lower cost. Sensitivity analysis showed that DFP dominated all other treatments unless the QoL burden associated with the route of administration was greater for DFP than for DFO, which is unlikely to be the case. DFP had >99 % likelihood of being cost effective against all comparators at a willingness-to-pay threshold of £20,000 per QALY. In this
Exline, David L; Wallace, Christie; Roux, Claude; Lennard, Chris; Nelson, Matthew P; Treado, Patrick J
Chemical imaging technology is a rapid examination technique that combines molecular spectroscopy and digital imaging, providing information on morphology, composition, structure, and concentration of a material. Among many other applications, chemical imaging offers an array of novel analytical testing methods, which limits sample preparation and provides high-quality imaging data essential in the detection of latent fingerprints. Luminescence chemical imaging and visible absorbance chemical imaging have been successfully applied to ninhydrin, DFO, cyanoacrylate, and luminescent dye-treated latent fingerprints, demonstrating the potential of this technology to aid forensic investigations. In addition, visible absorption chemical imaging has been applied successfully to visualize untreated latent fingerprints.
whale Fin whale Gray whale Humpback Killer whale Date VES Launch site Pers Activity Beg End Hours Nmi S# Tot IDs S# Tot IDs S# Tot IDs S# Tot IDs S...Humpback whale identifications are being compiled by DFO. Blue whale Fin whale Gray whale Humpback Killer whale Sperm whale Date VES Pers Beg End... Puget Sound 79 0 0 0 2 0 0 0 0 0 2 0 0 1 0 0 0 0 0 0 5 All 20 91 150 213 111 218 282 398 257 260 365 366 290 435 388 269 308 346 398 1,565
ELEMENT NUMBER 6. AUTHOR( S ) Ridley, Aaron J. 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND...ORGANIZATION REPORT NUMBER P/G # F030769 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) USAF, AFRL DUNS 143574726 AF OFFICE OF SCIENTIFIC...RESEARCH 875 NORTH RANDOLPH STREET, RM 31 12 ARLINGTON VA 22203 MALINDA E. ROGERS 703.696-1140 10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR/MONITOR’S
Major General J.A. Abrahamson, right, talks to JSC Director Christopher C. Kraft, Jr., (seated left) and Space Shuttle Program Manager Glynn S. Lunney on the back row of consoles in the mission operations control room (MOCR) in the Johnson Space Center mission control center. The reflection behind the men is a window for the MOCR viewing room (28772,28775); Abrahamson, second right, talks to JSC's Aaron Cohen, right, as Kraft (seated left) and Lunney listen in mission control (28773); Flight controller J.E. Connor monitors a television transmission from the Space Shuttle Columbia during day 4 of the STS-3 mission. Conner is seated at his INCO console (28774).
Kotte, Amelia; Hill, Kaitlin A; Mah, Albert C; Korathu-Larson, Priya A; Au, Janelle R; Izmirian, Sonia; Keir, Scott S; Nakamura, Brad J; Higa-McMillan, Charmaine K
This study examines implementation facilitators and barriers of a statewide roll-out of a measurement feedback system (MFS) in a youth public mental health system. 76 % of all state care coordinators (N = 47) completed interviews, which were coded via content analysis until saturation. Facilitators (e.g., recognition of the MFS's clinical utility) and barriers (e.g., MFS's reliability and validity) emerged paralleling the Exploration, Adoption/Preparation, Implementation, and Sustainment framework outlined by Aarons et al. (Adm Policy Mental Health Mental Health Serv Res, 38:4-23, 2011). Sustainment efforts may leverage innovation fit, individual adopter, and system related facilitators.
Revolution.” 397 David Blair and Richard Spencer , “How Qatar Is Funding the Rise of Islamist Extremists,” The Telegraph, September 20, 2014, http...Islamists in Syria, Officials Say;” Spencer , “How Qatar Is Funding the Rise of Islamist Extremists.” 411 Amena Bakr, “Defying Allies, Qatar Unlikely...Ibid. 416 Spencer , “How Qatar Is Funding the Rise of Islamist Extremists.” 417 Thomas Hegghammer and Aaron Y. Zelin, “How Syria’s Civil War Became a
Charles Wald , “The Phase Zero Campaign,” Joint Force Quarterly, Issue 43, 4th Quarter 2006, available at http://www.ndu.edu/inss. 12 DOD, The Quadrennial...Deputy Under Secretary Henry From the Pentagon,” February 7, 2007. 19 See, for example, Lisa Schirch and Aaron Kishbaugh, “Leveraging ‘3D’ Security...Testimony of General Charles Wald , Member, Military Advisory Board, at a hearing on Climate Change and National Security Threats by the Senate Foreign
members, Marines Gunnery Sgt William Bockelman and Sgt Nathaniel Bruce , and Airmen TSgt Aaron McLane and SSgt Anthony McMurtry. During the relay... Bruce of the SAM Squad encourage SSgt Anthony McMurtry during the mannequin pull. Gunnery Sgt Eric Aker of the SAM Squad catches his breath following...the 45th CES at Patrick AFB by MSgt Efrain Gonzalez; (below, L– R ) SrA Robert Ryon of 202nd RHS by Sgt Sarah Maxwell; snapped power pole at Eglin
Wightman, Aaron; Largent, Emily; Del Beccaro, Mark; Lantos, John D
Administrators sometimes face ethical dilemmas about the allocation of institutional resources. One such situation is when elective surgery cases require reserved ICU beds and the ICU is full. Such situations arise frequently in children's hospitals today. They are sometimes complicated by questions about whether every patient in the ICU belongs there. We present such a situation and responses from Mark Del Becarro, Vice President for Medical Affairs at Seattle Children's Hospital; Aaron Wightman, a nephrology fellow and bioethicist at Seattle Children's Hospital; and Emily Largent, a doctoral student in the joint JD/PhD Program in Health Policy at Harvard University. Copyright © 2014 by the American Academy of Pediatrics.
Yesavage, J A
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.
Hesse, and M. Alexe, Phys. Rev. Lett. 98, 257601 (2007).  P. Emma, R. Akre , J. Arthur, R. Bionta, C. Bostedt, J. Bozek, A . Brachmann, P...David M. Fritz10, Marco Cammarata10, Diling Zhu10, Henrik T. Lemke10,11, Donald A . Walko4, Eric M. Dufresne4, Yuelin Li4, Jörgen Larsson12, David A ...Reis2,9,13, Klaus Sokolowski-Tinten7, Keith A . Nelson6, Andrew M. Rappe5, Paul H. Fuoss3, G. Brian Stephenson3 and Aaron M. Lindenberg2,8.9
for some reason, once I put that uniform on, or once I walked into that clubhouse , no matter what happened at home, I could totally get focused. I...focusing.” What does that mean to you? Aaron: That means tuning out everything else. You get to the ballpark sometimes and you see three or four guys...in on what they have to do. When you get to the ballpark, you ought to be able to get yourself in tune to knowing who the pitcher is that you’re
Crystal Brockington and Aaron Barron, both 18 years old, designed a more efficient and cost effective solar cell that harnesses energy without cadmium, which has been shown to be harmful to the environment. They were selected to participate in the White House Science Fair after they were awarded the High School Grand Prize at the Siemens We Can Change the World Challenge. The fourth White House Science Fair was held at the White House on May 27, 2014 and included 100 students from more than 30 different states who competed in science, technology, engineering, and math (STEM) competitions. (Photo Credit: NASA/Aubrey Gemignani)
CSLC E N T E R f o r S T R AT E G I C L E A D E R S H I P Student Issue PaperCenter for Strategic Leadership, U.S...Matthew Batson was commanding L Troop, 4th U.S. Cavalry, during operations in the Philippines. Already recognized as an energetic and courageous officer...Said England unto Pharaoh, “You’ve had miracles before, When Aaron struck your rivers into blood; But if you watch the Sergeant he can show you
KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy (right) talks to Aaron Fernander, principal of Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. Kennedy is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. He was accompanied by astronaut Rick Linnehan on the visit. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.
Encarnação, Paula; Oliveira, Clara C; Martins, Teresa
Based on Aaron Antonovsky's salutogenic model, the authors of this article aim to analyze the term Faith as a Generalized Resistance Resource (GRR) of people's health and to delve the relevance of this construct to clinical practice in Nursing. The authors consider that, in order for nurses to intervene in the promotion of faith so as to bring health benefits to people, a solid educational training in this subject area is required by nursing students. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.
Morikis UCR CHUNSHENG WANG University of California San Francisco Christopher Druzgalski PAHCE Jeffrey Chen UC Riverside BRITE Adriana Aguirre UC...Diagnosis B23 Foad Mashayekhi, Aaron S. Meyer, Stacey A. Shiigi, Vu Nguyen and Daniel T. Ka - 129 meL UCLA B24 Self-Assembly and DNA Binding Properties of...Journal of Immunclogy 165:3839 3848. 2Hannan JP, Young KA , Guthrid!le JM, Asokan R, Szakonyi G, Chen XJS, & Holers \\1M (2005) Journal of Molecular
Michkov AV, Lynch RM, Overland AC, Corriden R. G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic...M. Chinn, Alexander V. Michkov, Rebecca M. Lynch , Aaron C. Overland, and Ross Corriden Departments of Pharmacology (P.A.I., A.W., A.C.Z., A.N.S., N.A...Sriram, Chinn, Michkov, Lynch , Overland, Corriden. References Ahmad R, Wojciech S, Jockers R (2014) Hunting for the function of orphan GPCRs - beyond
8 the more flexible policies found in many management tasks must be made in an ad - hoc fashion at the application level, leading to a loss of user...this mismatch as a significant source of disorganization: Aaron: “I’m very conscious about the way I name things; I have a coding system. But the...thing is, that doesn’t work if you have everything spread out. The coding system makes sense when there’s a lot of other things around, but not when it’s
After the keynote presentation by Professor Aaron Cohen of Texas A and M University, entitled Processes Used in Design, the program is divided into five major sessions: Research and Development -- Recent research and development of tribological components; Tribology in Manufacturing -- The impact of tribology on modern manufacturing; Design/Design Representation -- Aspects of design related to tribological systems; Tribo-Chemistry/Tribo-Physics -- Discussion of chemical and physical behavior of substances as related to tribology; and Failure Analysis -- An analysis of failure, failure detection, and failure monitoring as related to manufacturing processes. Papers have been processed separately for inclusion on themore » data base.« less
origins of SF. Colonel (retired) Aaron Bank’s book From OSS to the Green Berets gave a first-hand appreciation of the origins of SF from World War II to...improved and implemented in World War II. The model was to weaken the enemy’s front line, weaken the enemy’s infrastructure, and win the support of the...Marauders, and Lieutenant General Walter Krueger’s Alamo Scouts as the elite units that successfully conducted unconventional warfare during World War II
Wang, Sheng; Gai, Yongkang; Zhang, Shasha; Ke, Lei; Ma, Xiang; Xiang, Guangya
Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Larcher, Gérald; Dias, Marylène; Razafimandimby, Bienvenue; Bomal, Danielle; Bouchara, Jean-Philippe
Clinical reports have established that mucormycosis, mainly caused by Rhizopus spp., frequently occurs in patients treated with deferoxamine B (DFO, Desferal(®)) which is misappropriated by these fungi. Siderophore production by twenty mucoralean isolates was therefore investigated using a commercial iron-depleted culture medium. Siderophore production was detected for most of the isolates. Our experiments confirmed that feroxamine B (iron chelate of DFO) promoted in vitro growth of Rhizopus arrhizus. Electrophoretic analysis of somatic extracts revealed iron-regulated proteins of 60 and 32 kDa which were lacking in iron-depleted culture conditions. Using a fluorescent derivative of deferoxamine B, we showed by fluorescence microscopy the entry of the siderophore within the fungal cells, thus suggesting a shuttle mechanism encompassing the uptake of the entire siderophore-ion complex into the cell. This useful tool renders possible a better understanding of iron metabolism in Mucorales which could lead to the development of new diagnostic method or new antifungal therapy using siderophores as imaging contrast agents or active drug vectors.
Krause, F; Barandun, A; Klammer, G; Zderic, I; Gueorguiev, B; Schmid, T
To assess the effect of high tibial and distal femoral osteotomies (HTO and DFO) on the pressure characteristics of the ankle joint. Varus and valgus malalignment of the knee was simulated in human cadaver full-length legs. Testing included four measurements: baseline malalignment, 5° and 10° re-aligning osteotomy, and control baseline malalignment. For HTO, testing was rerun with the subtalar joint fixed. In order to represent half body weight, a 300 N force was applied onto the femoral head. Intra-articular sensors captured ankle pressure. In the absence of restriction of subtalar movement, insignificant migration of the centre of force and changes of maximal pressure were seen at the ankle joint. With restricted subtalar motion, more significant lateralisation of the centre of force were seen with the subtalar joint in varus than in valgus position. Changes in maximum pressure were again not significant. The re-alignment of coronal plane knee deformities by HTO and DFO altered ankle pressure characteristics. When the subtalar joint was fixed in the varus position, migration of centre of force after HTO was more significant than when the subtalar joint was fixed in valgus. Cite this article: Bone Joint J 2017;99-B:59-65. ©2017 The British Editorial Society of Bone & Joint Surgery.
This report summarizes two projects covered under an Interagency Agreement between the Bureau of Safety and Environmental Enforcement (BSEE) and the U.S. Environmental Protection Agency (EPA) in collaboration with the Bedford Institute of Oceanography, Department of Fisheries and Oceans Canada (BIO DFO), New Jersey Institute of Technology (NJIT) and Dalhousie University. Both projects dovetail together in addressing the ability to differentiate physical from chemical dispersion effectiveness using dispersed oil simulations within a flume tank for improving forensic response monitoring tools. This report is split into separateTasks based upon the two projects funded by BSEE: 1) Dispersant Effectiveness, In-Situ Droplet Size Distribution and Numerical Modeling to Assess Subsurface Dispersant Injection as a Deepwater Blowout Oil Spill Response Option. 2) Evaluation of Oil Fluorescence Characteristics to Improve Forensic Response Tools. This report summarizes 2 collaborative projects funded through an Interagency Agreement with DOI BSEE and a Cooperative Agreement with DFO Canada. BSEE required that the projects be combined into one report as they are both covered under the one Interagency Agreement. Task B (Fluorescence of oils) is an SHC 3.62 FY16 product.
Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.
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.
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.
Kraemer, Stephan M; Xu, Jide; Raymond, Kenneth N; Sposito, Garrison
Trihydroxamate siderophores have been proposed for use as mediators of actinide and heavy metal mobility in contaminated subsurface zones. These microbially produced ligands, common in terrestrial and marine environments, recently have been derivatized synthetically to enhance their affinity for transuranic metal cations. However, the interactions between these synthetic derivative and adsorbed trace metals have not been characterized. In this paper we compare a natural siderophore, desferrioxamine-B (DFO-B), with its actinide-specific catecholate derivative, N-(2,3-dihydroxy-4-(methylamido)benzoyl)desferrioxamine-B (DFOMTA), as to their effect on the adsorption of Pb(II) and Eu(III) by goethite and boehmite. In the presence of 240 microM DFO-B, a strongly depleting effect on Eu(III) adsorption by goethite and boehmite occurred above pH 6. By contrast, almost total removal of Eu(III) from solution in the neutral to slightly acidic pH range was observed in the presence of either 10 or 100 microM DFOMTA, due primarilyto the formation of metal-DFOMTA precipitates. Addition of DFOMTA caused an increase in Pb(II) adsorption by goethite below pH 5, but a decrease above pH 5, such that the Pb(II) adsorption edge in the presence of DFOMTA strongly resembled the DFOMTA adsorption envelope, which showed a maximum near pH 5 and decreasing adsorption toward lower and higher pH.
Mink, Tineke; Voorhaar, Annelies; Stoel, Reinoud; de Puit, Marcel
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. Copyright © 2013 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.
Kim, You-Mie; Song, Insun; Seo, Yong-Hak; Yoon, Gyesoon
Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H2O2. In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3α and β also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.
Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.
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.
Breshears, Andrew T.; Brown, M. Alex; Bloom, Ira
We report a new method of crystal growth and synthesis based on liquid-liquid partitioning that allows for isolation and in-depth characterization of molybdenyl bis(formohydroxamate), Mo-FHA, molybdenyl bis(acetohydroxamate), Mo-AHA, and molybdenyl deferoxamine, Mo-DFO, for the first time. This novel approach affords shorter crystal growth time (hourly timeframe) without sacrificing crystal size or integrity when other methods of crystallization were unsuccessful. All three Mo complexes are characterized in solution via FTIR, NMR, UV-vis, and EXAFS spectroscopy. Mo-AHA and Mo-FHA structures are resolved by single crystal X-ray diffraction. Using the molybdenyl hydroxamate structural information, the speciation of Mo in a siderophore complex (Mo-DFO)more » is determined via complimentary spectroscopic methods and confirmed by DFT calculations. ESI-MS verifies that a complex of 1:1 molybdenum to deferoxamine is present in solution. Additionally, the Mo solution speciation in the precursor organic phase, MoO2(NO3)2HEH[EHP]2 (where HEH[EHP] is 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester), is characterized by FTIR and EXAFS spectroscopy as well as DFT calculations.« less
Payne, Gemma; Reedy, Brian; Lennard, Chris; Comber, Bruce; Exline, David; Roux, Claude
This study investigated the application of chemical imaging to the detection of latent fingerprints using the Condor macroscopic chemical imaging system (ChemImage Corp., Pittsburgh, USA). Methods were developed and optimised for the visualisation of untreated latent fingerprints and fingerprints processed with DFO, ninhydrin, cyanoacrylate, and cyanoacrylate plus rhodamine 6G stain. The results obtained with chemical imaging were compared to the detection achieved using conventional imaging techniques. The Condor significantly improved the detection of many prints, especially those that might be considered poor quality or borderline prints. Prints on newspaper treated with ninhydrin and DFO, and prints on white and yellow paper treated with ninhydrin, benefited the most from chemical imaging detection. In many cases, fingerprints undetectable using conventional imaging techniques could be visualised with chemical imaging. Ridge detail from untreated prints on yellow paper was also detected using the Condor. When prints of high quality were examined, both detection techniques produced quality results. The results of this project demonstrate that chemical imaging offers advantages over conventional visualisation techniques when examining latent fingerprints, especially those that would be considered difficult, such as weak prints or prints on surfaces that produce highly luminescent backgrounds. Standard testing procedures for the detection and enhancement of fingerprints by chemical imaging are presented and discussed.
Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.
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
Graff, L; Muller, G; Burnel, D
The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.
Mosayebnia, Mona; Shafiee-Ardestani, Mehdi; Pasalar, Parvin; Mashayekhi, Mojgan; Amanlou, Massoud
To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. 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. 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. 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.
Pierce, Aaron T.
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 ofmore » 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.« less
Lucio-Eceiza, E. E.; González-Rouco, J. F.; Navarro, J.; Beltrami, H.; Jiménez, P. A.; García-Bustamante, E.; Hidalgo, A.
This work summarizes the results of a Quality Assurance (QA) procedure applied to wind data centred over a wide area in Eastern Canada. The region includes the provinces of Quebec, Prince Edward Island, New Brunswick, Nova Scotia, Newfoundland, Labrador and parts of the north-eastern U.S. (Maine, New Hampshire, Massachusetts, New York and Vermont). The data set consists of 527 stations compiled from three different sources: 344 land sites from Environment Canada (EC; 1940-2009), 40 buoys distributed over the East Coast and the Canadian Great Lakes provided by the Department of Fisheries and Oceans (DFO; 1988-2008), and 143 land sites over both eastern Canada and north-eastern U.S. provided by the National Center of Atmospheric Research (NCAR; 1975-2007). The complexity of the QA process is enhanced in this case by the variety of institutional observational protocols that lead to different temporal resolutions (hourly, 3-h and 6-h), unit systems (km/h in EC; m/s in DFO and knots in NCAR), time references (e.g. UTC, UTC+1, UTC-5, UTC-4), etc. Initial corrections comprised the establishment of common reference systems for time (UTC) and units (MKS). The QA applied on the resulting dataset is structured in three steps that involve the detection and correction of: manipulation errors (i.e. repetitions); unrealistic values and ranges in wind module and direction; abnormally low (e.g. long constant periods) and high variations (e.g. extreme values and inhomogeneities). Results from the first step indicate 22 sites (8 EC; 14 DFO) showing temporal patterns that are unrealistically repeated along the stations. After the QA is applied, the dataset will be subject to statistical and dynamical downscaling studies. The statistical approaches will allow for an understanding of the wind field variability related to changes in the large scale atmospheric circulation as well as their dependence on local/regional features like topography, land-sea contrasts, snow/ice presence, etc
Williams, Richelle M; Corvo, Matthew A; Lam, Kenneth C; Williams, Travis A; Gilmer, Lesley K; McLeod, Tamara C Valovich
Postural control plays an essential role in concussion evaluation. The Stability Evaluation Test (SET) aims to objectively analyze postural control by measuring sway velocity on the NeuroCom's VSR portable force platform (Natus, San Carlos, CA). To assess the test-retest reliability and practice effects of the SET protocol. Cohort. Research Laboratory. Fifty healthy adults (males=20, females=30, age=25.30±3.60 years, height=166.60±12.80 cm, mass=68.80±13.90 kg). All participants completed four trials of the SET. Each trial consisted of six 20-second balance tests with eyes closed, under the following conditions: double-leg firm (DFi), single-leg firm (SFi), tandem firm (TFi), double-leg foam (DFo), single-leg foam (SFo), and tandem foam (TFo). Each trial was separated by a 5-minute seated rest period. The dependent variable was sway velocity (deg/sec), with lower values indicating better balance. Sway velocity was recorded for each of the six conditions as well as a composite score for each trial. Test-retest reliability was analyzed across four trials with Intraclass Correlation Coefficients. Practice effects analyzed with repeated measures analysis of variance, followed by Tukey post-hoc comparisons for any significant main effects (p<.05). Sway velocity reliability values were good to excellent: DFi (ICC=0.88;95%CI:0.81,0.92), SFi (ICC=0.75;95%CI:0.61,0.85), TFi (ICC=0.84;95%CI:0.75,0.90), DFo (ICC=0.83;95%CI:0.74,0.90), SFo (ICC=0.82;95%CI:0.72,0.89), TFo (ICC=0.81;95%CI:0.69,0.88), and composite score (ICC=0.93;95%CI:0.88,0.95). Significant practice effects (p<.05) were noted on the SFi, DFo, SFo, TFo conditions, and composite scores. Our results suggest the SET has good to excellent reliability for the assessment of postural control in healthy adults. Due to the practice effects noted, a familiarization session is recommended (i.e., all 6 conditions) prior to recording the data. Future studies should evaluate injured patients to determine meaningful change
Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B.; Kalinowski, Danuta S.; Lovejoy, David B.; Lane, Darius J. R.; Richardson, Des R.
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 ± 2.00 μM, respectively) than DFO (IC50 = 23.43 ± 3.40 μM). 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 activity, 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. PMID:24028863
Bruni, Antonio; Pepper, Andrew R; Pawlick, Rena L; Gala-Lopez, Boris; Gamble, Anissa F; Kin, Tatsuya; Seeberger, Karen; Korbutt, Gregory S; Bornstein, Stefan R; Linkermann, Andreas; Shapiro, A M James
Human islet transplantation has been hampered by donor cell death associated with the islet preparation procedure before transplantation. Regulated necrosis pathways are biochemically and morphologically distinct from apoptosis. Recently, ferroptosis was identified as a non-apoptotic form of iron-dependent regulated necrosis implicated in various pathological conditions. Mediators of islet oxidative stress, including glutathione peroxidase-4 (GPX4), have been identified as inhibitors of ferroptosis, and mechanisms that affect GPX4 function can impact islet function and viability. Ferroptosis has not been investigated directly in human islets, and its relevance in islet transplantation remains unknown. Herein, we sought to determine whether in vitro human islet viability and function is compromised in the presence of two distinct ferroptosis-inducing agents (FIA), erastin or RSL3, and whether these effects could be rescued with ferroptosis inhibitors, ferrostatin-1 (Fer-1), or desferrioxamine (DFO). Viability, as assessed by lactate dehydrogenase (LDH) release, revealed significant death in erastin- and RSL3-treated islets, 20.3% ± 3.8 and 24.4% ± 2.5, 24 h post culture, respectively. These effects were ameliorated in islets pre-treated with Fer-1 or the iron chelator, desferrioxamine (DFO). Stimulation index, a marker of islet function revealed a significant reduction in function in erastin-treated islets (control 1.97 ± 0.13 vs. 50 μM erastin 1.32 ± 0.1) (p < 0.05). Fer-1 and DFO pre-treatment alone did not augment islet viability or function. Pre-treatment of islets with erastin or Fer-1 did not impact in vivo engraftment in an immunodeficient mouse transplant model. Our data reveal that islets are indeed susceptible to ferroptosis in vitro, and induction of this novel cell death modality leads to compromised islet function, which can be recoverable in the presence of the ferroptosis inhibitors. The in vivo impact of this pathway in
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Delattre, François; Cazier-Dennin, Francine; Leleu, Ludovic; Dewaele, Dorothée; Landy, David; Mallard, Isabelle; Danjou, Pierre-Edouard
This work reports on an efficient microwave irradiation synthesis of a new fluorescent chemosensor based on desferrioxamine B (DFO-B) and carbazole moiety. Furthermore, this novel chemosensor was employed for a comparative study of real environmental samples of airbone particulate matter collected from Dunkirk (Northern of France). Among selected relevant metal cations present in its airbone particulate matter, such as Na(+), K(+), Mg(2+), Ca(2+), Al(3+), Cr(3+), Mn(2+) and Zn(2+), this molecular device proved to be outstandingly sensitive toward Fe(3+) with a limit of detection of 1.49 ppb (2.1×10(-8) M) in methanol allowing the estimation of total iron in atmospheric particles. Copyright © 2015 Elsevier B.V. All rights reserved.
Eslick, John C.; Ng, Brenda; Gao, Qianwen; ...
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
Jitraruch, Suttiruk; Hughes, Robin D.; Filippi, Celine; Lehec, Sharon C.; Glover, Leanne; Mitry, Ragai R.
Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimized protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated. Human and rat hepatocytes cryopreserved with University of Wisconsin (UW)/10% dimethyl sulfoxide (DMSO)/5% (300 mM) glucose and CryoStor CS10 showed better postthawing cell viability, attachment, and hepatocyte functions than with histidine–tryptophan–ketoglutarate/10% DMSO/5% glucose and Bambanker. The 2 freezing solutions that gave better results were studied with human and rat hepatocytes microbeads. Similar effects on cryopreserved microbead morphology (external and ultrastructural), viability, and hepatocyte-functions post thawing were observed over 7 d in culture. UW/DMSO/glucose, as a basal freezing medium, was used to investigate the additional effects of cytoprotectants: a pan-caspase inhibitor (benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone [ZVAD]), an antioxidant (desferoxamine [DFO]), and a buffering and mechanical protectant (human serum albumin [HSA]) on RMBs. ZVAD (60 µM) had a beneficial effect on cell viability that was greater than with DFO (1 mM), HSA (2%), and basal freezing medium alone. Improvements in the ultrastructure of encapsulated hepatocytes and a lower degree of cell apoptosis were observed with all 3 cytoprotectants, with ZVAD tending to provide the greatest effect. Cytochrome P450 activity was significantly higher in the 3 cytoprotectant groups than with fresh microbeads. In conclusion, developing an optimized cryopreservation protocol by adding
Douglas, K. L.; Hillier, M. C. J.; Thornborough, K. J.; Jenkyns, R.; Juniper, K.
The Endeavour Hydrothermal Vents Marine Protected Area (EHVMPA) is located approximately 250 km offshore of Vancouver Island, British Columbia. Since its discovery in 1982, there have been hundreds of dives, samples collected, measurements made, and debris left behind at the EHVMPA. In 2003, the Canadian government declared the region as a Marine Protected Area (MPA) under Canada's Oceans Act, to be managed by the Department of Fisheries and Oceans (DFO). Ocean Networks Canada (ONC) operates a cabled observatory in the EHVMPA, and streams data in near real-time via the Internet to science communities worldwide. ONC's observatory data, combined with observations made during maintenance expeditions provides insight assisting the management and preservation of the MPA. In 2014, DFO partnered with ONC to build a geodatabase to enhance and inform the knowledge base of the EHVMPA Management Plan. The geodatabase, built in ArcGIS, contains data integrated from ONC's Oceans 2.0 database, third parties, and relevant publications. Layers include annual observatory infrastructure deployments, remotely operated vehicle (ROV) dive tracks, sampling activity, anthropogenic debris, high-resolution bathymetry, observations of species of interest, and locations of hydrothermal vents. The combined data show both efforts to better understand the environment and the resulting stressors that impact the MPA. The tool also links observed features such as debris and biological observations to the time-correlated ROV dive video using ONC's SeaTube video viewing tool allowing for further analysis. Through 2017, the geodatabase will be maintained by ONC and enriched with expedition data from organizations such as Monterey Bay Aquarium Research Institute, Woods Hole Oceanographic Institute, and the University of Washington. The end result is a tool that can integrate many types of data obtained from the MPA, and encourages systematic management of a remote, dynamic and fragile environment.
Tellman, B.; Sullivan, J.; Kettner, A.; Brakenridge, G. R.; Slayback, D. A.; Kuhn, C.; Doyle, C.
There is an increasing need to understand flood vulnerability as the societal and economic effects of flooding increases. Risk models from insurance companies and flood models from hydrologists must be calibrated based on flood observations in order to make future predictions that can improve planning and help societies reduce future disasters. Specifically, to improve these models both traditional methods of flood prediction from physically based models as well as data-driven techniques, such as machine learning, require spatial flood observation to validate model outputs and quantify uncertainty. A key dataset that is missing for flood model validation is a global historical geo-database of flood event extents. Currently, the most advanced database of historical flood extent is hosted and maintained at the Dartmouth Flood Observatory (DFO) that has catalogued 4320 floods (1985-2015) but has only mapped 5% of these floods. We are addressing this data gap by mapping the inventory of floods in the DFO database to create a first-of- its-kind, comprehensive, global and historical geospatial database of flood events. To do so, we combine water detection algorithms on MODIS and Landsat 5,7 and 8 imagery in Google Earth Engine to map discrete flood events. The created database will be available in the Earth Engine Catalogue for download by country, region, or time period. This dataset can be leveraged for new data-driven hydrologic modeling using machine learning algorithms in Earth Engine's highly parallelized computing environment, and we will show examples for New York and Senegal.
Schuschereba, Steven T.; Cross, Michael E.; Scales, David K.; Pizarro, Jose M.; Edsall, Peter R.; Stuck, Bruce E.; Marshall, John
Purpose. To evaluate therapeutics for attenuating retinal laser injury. Methods. New Zealand Red rabbits (n=76) were pretreated (IV) with either a single dose of hydroxyethyl starch conjugated deferoxamine (HES-DFO, n=29) (6.1 ml/kg, 16.4 mg/ml) or methylprednisolone sodium succinate (MP, n=22) (30 mg/kg, followed by taper of 30, 20, 20, and 10 mg/kg/day for a total of 5d). Controls were untreated (n=25). Fifteen min later, animals were irradiated with a multiline cw argon laser (285 mW, 10 msec pulse durations, 16 lesions/eye). Funduscopy, fluorescein angiography, histology, and morphometry were performed at 10 min, 1h, 3h, 24h, 1 mo, and 6 mo after irradiation. Leukocytes were counted at lesion centers for retinal and choroidal compartments at 1, 3, and 24h. Results. At 3h, percent area incrase for the lesions was highest for MP (44%) and lowest for HES-DFO (16%)(p<0.05). In hemorrhagic lesions, MP treatment resulted in the highest increase of retinal neotrophils by 24h (p<0.05), and by 1 and 6 mo extensive chorio-retinal scarring occurred in nonhemorrhagic and hemorrhagic lesions. Also, no benefit was demonstrated on sparing of photoreceptors with MP treatment. Conclusions. Treatment of laser-induced retinal injury with methylprednisolone (MP) exacerbates acute inflammation and long-term chorio-retinal scarring; however, hydroxyethyl starch conjugated deferoxamine therapy ameliorates these aspects of injury. Data suggest caution in the use of MP therapy for laser injuries.
Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas
To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110
Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas
To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.
Imrich, Amy; Ning, YaoYu; Lawrence, Joy; Coull, Brent; Gitin, Elena; Knutson, Mitchell; Kobzik, Lester
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 microM) 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(2)O(2) generated by glucose oxidase, 10 microM/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(2)O(2). The metal chelator deferoxamine (DFO) strongly inhibited the interaction of the soluble fraction with H(2)O(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(2)O(2)-dependent (catalase-sensitive) yet independent of iron (DFO-insensitive). In the presence of exogenous H(2)O(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.
Kontoghiorghe, Christina N; Kontoghiorghes, George J
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
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
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. © 2015 by The American Society of Hematology.
Najibi, Nasser; Devineni, Naresh
Frequency and duration of floods are analyzed using the global flood database of the Dartmouth Flood Observatory (DFO) to explore evidence of trends during 1985-2015 at global and latitudinal scales. Three classes of flood duration (i.e., short: 1-7, moderate: 8-20, and long: 21 days and above) are also considered for this analysis. The nonparametric Mann-Kendall trend analysis is used to evaluate three hypotheses addressing potential monotonic trends in the frequency of flood, moments of duration, and frequency of specific flood duration types. We also evaluated if trends could be related to large-scale atmospheric teleconnections using a generalized linear model framework. Results show that flood frequency and the tails of the flood duration (long duration) have increased at both the global and the latitudinal scales. In the tropics, floods have increased 4-fold since the 2000s. This increase is 2.5-fold in the north midlatitudes. However, much of the trend in frequency and duration of the floods can be placed within the long-term climate variability context since the Atlantic Multidecadal Oscillation, North Atlantic Oscillation, and Pacific Decadal Oscillation were the main atmospheric teleconnections explaining this trend. There is no monotonic trend in the frequency of short-duration floods across all the global and latitudinal scales. There is a significant increasing trend in the annual median of flood durations globally and each latitudinal belt, and this trend is not related to these teleconnections. While the DFO data come with a certain level of epistemic uncertainty due to imprecision in the estimation of floods, overall, the analysis provides insights for understanding the frequency and persistence in hydrologic extremes and how they relate to changes in the climate, organization of global and local dynamical systems, and country-scale socioeconomic factors.
Chazan, J A; Libbey, N P; London, M R; Pono, L; Abuelo, J G
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.
Wylie, James D; Jones, Daniel L; Hartley, Melissa K; Kapron, Ashley L; Krych, Aaron J; Aoki, Stephen K; Maak, Travis G
(1) To determine the radiographic correction/healing rate, patient-reported outcomes, reoperation rate, and complication rate after distal femoral osteotomy (DFO) for the valgus knee with lateral compartment pathology. (2) To summarize the reported results of medial closing wedge and lateral opening wedge DFO. We conducted a systematic review of PubMed, MEDLINE, and CINAHL to identify studies reporting outcomes of DFOs for the valgus knee. Keywords included "distal femoral osteotomy," "chondral," "cartilage," "valgus," "joint restoration," "joint preservation," "arthritis," and "gonarthrosis." Two authors first reviewed the articles; our study exclusion criteria were then applied, and the articles were included on the basis relevance defined by the aforementioned criteria. The Methodological Index for Nonrandomized Studies scale judged the quality of the literature. Sixteen studies were relevant to the research questions out of 191 studies identified by the original search. Sixteen studies were identified reporting on 372 osteotomies with mean follow-up of 45 to 180 months. All studies reported mean radiographic correction to a near neutral mechanical axis, with 3.2% nonunion and 3.8% delayed union rates. There was a 9% complication rate and a 34% reoperation rate, of which 15% were converted to arthroplasty. There were similar results reported for medial closing wedge and lateral opening wedge techniques, with a higher conversion to arthroplasty in the medial closing wedge that was confounded by longer mean follow-up in this group (mean follow-up 100 v 58 months). DFOs for the valgus knee with lateral compartment disease provide improvements in patient-reported knee health-related quality of life at midterm follow-up but have high rates of reoperation. No evidence exists proving better results of either the lateral opening wedge or medial closing wedge techniques. Level IV, systematic review of Level IV studies. Copyright © 2016 Arthroscopy Association of North
Kettner, A. J.; Brakenridge, G. R.; van Praag, E.; de Groeve, T.; Slayback, D. A.; Cohen, S.
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
Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A
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. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Bastian, Thomas W.; Duck, Kari A.; Michalopoulos, George C.; Chen, Michael J.; Liu, Zhi-Jian; Connor, James R.; Lanier, Lorene M.; Sola-Visner, Martha C.; Georgieff, Michael K.
Background Thrombocytopenia is common in sick neonates. Thrombopoietin mimetics (e.g., eltrombopag (ELT)) might provide an alternative therapy for selected neonates with severe and prolonged thrombocytopenia, and for infants and young children with different varieties of thrombocytopenia. However, ELT chelates intracellular iron, which may adversely affect developing organs with high metabolic requirements. Iron deficiency (ID) is particularly deleterious during brain development, impairing neuronal myelination, dopamine signaling, and dendritic maturation and ultimately impairing long-term neurological function (e.g. hippocampal-dependent learning and memory). Objective Determine whether ELT crosses the blood-brain barrier (BBB), causes neuronal ID and impairs hippocampal neuron dendrite maturation. Methods ELT transport across the BBB was assessed using primary bovine brain microvascular endothelial cells. Embryonic mouse primary hippocampal neuron cultures were treated with ELT or deferoxamine (DFO, an iron chelator) from 7 days in vitro (DIV) through 14DIV and assessed for gene expression and neuronal dendrite complexity. Results ELT crossed the BBB in a time-dependent manner. 2 and 6 μM ELT increased Tfr1 and Slc11a2 (iron-responsive genes involved in neuronal iron uptake) mRNA levels, indicating neuronal ID. 6 μM ELT, but not 2 μM ELT, decreased BdnfVI, Camk2a, and Vamp1 mRNA levels, suggesting impaired neuronal development and synaptic function. Dendrite branch number and length was reduced in 6 μM ELT-treated neurons, resulting in blunted dendritic arbor complexity that was similar to DFO-treated neurons. Conclusions ELT treatment during development may impair neuronal structure due to neuronal ID. Pre-clinical in vivo studies are warranted to assess ELT safety during periods of rapid brain development. PMID:28005311
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
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.
Finger, Stanley; Hustwit, Meredith P
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.
Gleacher, Alissa A.; Olin, Serene S.; Nadeem, Erum; Pollock, Michele; Ringle, Vanesa; Bickman, Leonard; Douglas, Susan; Hoagwood, Kimberly
Measurement feedback systems (MFSs) have been proposed as a means of improving practice. The present study examined the implementation of a MFS, the Contextualized Feedback System (CFS), in two community-based clinic sites. Significant implementation differences across sites provided a basis for examining factors that influenced clinician uptake of CFS. Following the theoretical implementation framework of Aarons, Hurlburt & Horwitz (2011), we coded qualitative data collected from eighteen clinicians (13 from Clinic U and 5 from Clinic R) who participated in semi-structured interviews about their experience with CFS implementation. Results suggest that clinicians at both clinics perceived more barriers than facilitators to CFS implementation. Interestingly, clinicians at the higher implementing clinic reported a higher proportion of barriers to facilitators (3:1 vs. 2:1); however, these clinicians also reported a significantly higher level of organizational and leadership supports for CFS implementation. Implications of these findings are discussed. PMID:25735619
Little, Edward E.; Greenberg, Bruce M.; DeLonay, Aaron J.
This publication, Environmental Toxicology and Risk Assessment: Seventh Volume, contains papers presented at the Seventh Symposium on Toxicology and Risk Assessment: Ultraviolet Radiation and the Environment, held 7-9 April, 1997 in St. Louis, MO. The symposium, the 24th in a series on environmental toxicology, was sponsored by Committee E-47. Edward E. Little, of the U.S. Geological Survey/Biological Services Division in Columbia, MO, presided as chairman of the symposium. Bruce M. Greenberg, with the Department of Biology at the University of Waterloo in Ontario, Canada, and Aaron J. DeLonay, also with the U.S. Geological Service/Biological Services Division in Columbia, MO, served as co-chairmen of the symposium. Each of these men served as editor of the resulting publication.
Onega, L L
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.
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.
Lindström, Bengt; Eriksson, Monica
The editor of the journal has taken the initiative to develop glossaries on central concepts in health promotion. The aim of this paper is to explain and clarify the key concepts of the salutogenic theory sense of coherence coined by Aaron Antonovsky. The explanations and interpretations are the result of an analysis of the scientific evidence base of the first 25 years of salutogenic research, described and discussed in an ongoing project on a systematic review by the above authors. The contemporary evidence shows the salutogenic approach could have a more central position in public health and health promotion research and practice. Furthermore, it could contribute to the solution of some of the most urgent public health problems of our time such as the question of mental health promotion. Finally, it could create a solid theoretical framework for health promotion.
Glorioso, Brad M.; Steece, Aaron; Lemann, Zachary K.; Lazare, Remy; Beck, James W.
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.
McCarty, Elizabeth; Morress, Claire
Children with a diagnosis of cerebral palsy often have significant physical limitations that prevent exploration and full participation in the environment. Assistive technology systems can provide opportunities for children with physical limitations to interact with their world, enabling play, communication, and daily living skills. Efficient access to and control of the technology is critical for successful use; however, establishing consistent access is often difficult because of the nature of the movement patterns exhibited by children with cerebral palsy. This article describes a 3-phase model of evaluation and intervention developed and used by Assistive Technology Services at the Aaron W. Perlman Center, Cincinnati Children's Hospital Medical Center, to establish successful access to technology systems in children with cerebral palsy.
KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy (center) and Principal Aaron Fernander (right) visit a classroom in Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. At left is Ralph Thomas, assistant administrator for Small and Disadvantaged Business Utilization at NASA. Kennedy is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. He was accompanied by astronaut Rick Linnehan on the visit. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.
Oh, Sangkyo; Lee, Kyungho
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
Oh, Sangkyo; Lee, Kyungho
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.
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.
Alexander, Aaron D.; Stoenner, Herbert G.; Wood, Garnett E.; Byrne, Robert J.
Alexander, Aaron D. (Walter Reed Army Institute of Research, Washington, D.C.), Herbert G. Stoenner, Garnett E. Wood, and Robert J. Byrne. A new pathogenic Leptospira, not readily cultivated. J. Bacteriol. 83:754–760. 1962.—A pathogenic Leptospira was isolated from water of the Grand River, (S.D.) that differed significantly from other known leptospirae in that it could not be cultivated in conventional leptospiral media. Growth was promoted in Fletcher's medium modified to contain 20% rabbit serum. The isolate, after several serial passages, was lethal for hamsters. It could not be adapted to grow in the chick embryo. Guinea pigs and calves inoculated with the isolate developed febrile and antibody responses but showed no other overt signs of disease. The strain was identified on the basis of cross-agglutination and agglutinin-adsorption tests as a new subserotype of Leptospira naam and was therefore designated as L. naam, subserotype dakotii. PMID:13860321
access 30 0~ LJ 0 CD 0 ( 4c CD - V2 0 C.2 ~~CD.------ 0.0 4-J V) 0 0.0 C.,I Cdc = CC, 0 0D C2 =I . 31 haua La OC I- c C _g .- C2 n C2 __. 6.34 LIA ca D...Department Navy Military Personnel Command Washington, D.C. 20370 6. Director for HRM Plans and Policy (OP-IS0) 1 Human Resource Management Division...Washington, D.C. 20301 25. Dana French, CAPT, USN HD HRM Plans & Policy Branch Washington, D.C. 20301 26. Robert Aaron 820 Lamberton Drive Silver
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.
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
Valente, Thomas W; Palinkas, Lawrence A; Czaja, Sara; Chu, Kar-Hai; Brown, C Hendricks
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  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.
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.
In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a mission science briefing for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Aaron Ridley, CYGNSS constellation scientist in the Climate and Space Department at the University of Michigan in Ann Arbor, Michigan; and Mary Morris, doctoral student in the Department of Climate and Space Sciences and Engineering at the University of Michigan. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.
In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a mission science briefing for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Dr. Chris Ruf, CYGNSS principal investigator, Department of Climate and Space Sciences and Engineering at the University of Michigan; and Aaron Ridley, CYGNSS constellation scientist in the Climate and Space Department at the University of Michigan in Ann Arbor, Michigan. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.
Valente, Thomas W.; Palinkas, Lawrence A.; Czaja, Sara; Chu, Kar-Hai; Brown, C. Hendricks
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  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
Monti, Peter M; Miranda, Robert; Nixon, Kimberly; Sher, Kenneth J; Swartzwelder, H Scott; Tapert, Susan F; White, Aaron; Crews, Fulton T
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.
Bloom, Aaron; Townsend, Aaron; Palchak, David
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 bymore » Aaron Bloom, highlighting results of the Eastern Renewable Generation Integration Study.« less
Tour Leader: Indra Das, NYU Langone Medical Center, New York, NY Tour Guides: Hsui Ai, Indiana University School of Medicine, Indianapolis, IN Aaron Andersen, Indiana University School of Medicine, Indianapolis, IN Olga Volotoskova, NYU Langone Medical Center, New York, NY Participating Vendors: IBA PTW – New York RTI Electronics, Inc. Standard Imaging, Inc. Sun Nuclear Corporation Small fields are increasing used in specialized radiation treatments such as Gammaknife, Cyberknife, Tomotherapy, IMRT, VMAT, SRS and SBRT. Due to small field size electron transport creates lateral electronic disequilibrium and thus dosimetry could be very difficult. Microdetectors are used for small field dosimetrymore » which will be discussed in preface of this tour as below: Understanding small field e.g. meaning and definition of small field IAEA definition and approach Characteristics of microdetectors in terms of perturbation, recombination, correction Suitability of microdetectors in small field dosimetry.« less
An astonishing 99.6% of our Universe is dark. Observations indicate that the Universe consists of 70% of a mysterious dark energy and 25% of a yet unidentified dark matter component, and only 0.4% of the remaining ordinary matter is visible. Understanding the physics of this dark sector is the foremost challenge in cosmology today. Sophisticated simulations of the evolution of the Universe play a crucial task in this endeavor. Credits: Science: Hal Finkel, Salman Habib, Katrin Heitmann, Kalyan Kumaran, Vitali Morozov, Tom Peterka, Adrian Pope, Tim Williams, David Daniel, Patricia Fasel, Nicholas Frontiere and Zarija Lukic Visualization: Mark Herald, Josephmore » A. Insley, Aaron Knoll, Michael E. Papka, Venkatram Vishwanath and Eric C. Olson« less
In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a mission science briefing for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Dr. Chris Ruf, CYGNSS principal investigator, Department of Climate and Space Sciences and Engineering at the University of Michigan; Aaron Ridley, CYGNSS constellation scientist in the Climate and Space Department at the University of Michigan in Ann Arbor, Michigan; and Mary Morris, doctoral student in the Department of Climate and Space Sciences and Engineering at the University of Michigan. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.
Bray, Igor; Stelbovics, Andris
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.
Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre.
Gamberini, Maria Rita; De Sanctis, Vincenzo; Gilli, Giuseppe
273 patients with thalassaemia major followed from diagnosis in the Ferrara Centre were divided into 3 cohorts (C) according to the year of birth (C1=1954-1964, 85 patients; C2=1965-1974, 129 patients; C3=1975-2001, 59 patients) in order to study the trends of endocrine complications. Menarche occurred in 52 out of 112 patients (46%), without significant differences among the 3 groups, at the mean age of 13.9+/-1.4 years. Sixty-five percent of these patients had secondary amenorrhoea at the mean age of 18.8+/-3.7 years. In males complete pubertal development occurred in 48% of patients (C1:31%, C2: 44%, C3: 63%, p<0.05) followed by secondary hypogonadism in 24% of patients above 21 years of age. Primary (80%) and central 20%) hypothyroidism were diagnosed in 31% of patients (C1: 55%, C2: 31.5%, C3: 13.4%, p<0.05), diabetes mellitus (DM) in 17% of patients (C1: 28.6%, C2: 17.2%, C3: 3.4%, p<0.05), and hypoparathyroidism in 10.6% of cases (C1: 18.7%, C2: 10.1%, C3: 3.4%, p<0.05). No difference was found in patient mean age of diagnosis of hypothyroidism, DM or hypoparathyroidism (20.4+/-8.2 years, 19+/-5 yrs and 18.5+/-5.8 yrs respectively) but in all three groups age at diagnosis significantly increased over time (hypothyroidism and DM: p<0.001; hypoparathyroidism: p<0.01). Over time the prevalence of hypothyroidism, diabetes mellitus and hypoparathyroidism increased to 24.4%, 14.7%, and 6.7%, respectively, at the time of the study. Incidences peaked in the early 1980's, and declined in the following years (primary hypothyroidism from 6.5% in 1981 to 0.9% in 2007, p<0.01; DM from 3.9% in 1986 to 0.8% in 2007, p<0.05; hypoparathyroidism 2.4% in 1984 to 0% in 2007, p<0.01) and correlated with the decrease in annual mean serum ferritin levels in all patients (p<0.001). The main risk factors associated with endocrine complications were high serum ferritin levels, poor compliance with desferioxamine (DFO) therapy, early onset of transfusion therapy (only for hypogonadism
O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P
Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger
Bolloskis, Michael P.; Carvalho, Fabiana P.; Loo, George, E-mail: firstname.lastname@example.org
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),more » 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. - Highlights: • PEITC increased HO-1 expression in HCT116 cells. • PEITC-induced HO-1 upregulation was impaired in iron-depleted HCT116 cells. • Impairment of PEITC-induced HO-1 upregulation was
Matsumoto, Takeshi; Sato, Shota
Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20–30, 30–40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10–20 and 20–30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. PMID:25780087
Matsumoto, Takeshi; Sato, Shota
Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20-30, 30-40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10-20 and 20-30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf
Ruggiero, Alessandro; Holland, Jason P.; Lewis, Jason S.; Grimm, Jan
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
Queern, Stacy Lee; Aweda, Tolulope Aramide; Massicano, Adriana Vidal Fernandes; Clanton, Nicholas Ashby; El Sayed, Retta; Sader, Jayden Andrew; Zyuzin, Alexander; Lapi, Suzanne Elizabeth
An increasing interest in zirconium-89 ( 89 Zr) can be attributed to the isotope's half-life which is compatible with antibody imaging using positron emission tomography (PET). The goal of this work was to develop an efficient means of production for 89 Zr that provides this isotope with high radionuclidic purity and specific activity. We investigated the irradiation of yttrium sputtered niobium coins and compared the yields and separation efficiency to solid yttrium coins. The sputtered coins were irradiated with an incident beam energy of 17.5MeV or 17.8MeV providing a degraded transmitted energy through an aluminum degrader of 12.5MeV or 12.8MeV, respectively, with various currents to determine optimal cyclotron conditions for 89 Zr production. Dissolution of the solid yttrium coin took 2h with 50mL of 2M HCl and dissolution of the sputtered coin took 15-30min with 4mL of 2M HCl. During the separation of 89 Zr from the solid yttrium coins, 77.9 ± 11.2% of the activity was eluted off in an average of 7.3mL of 1M oxalic acid whereas for the sputtered coins, 91 ± 6% was eluted off in an average of 1.2mL of 1M oxalic acid with 100% radionuclidic purity. The effective specific activity determined via DFO-SCN titration from the sputtered coins was 108±7mCi/μmol as compared to 20.3mCi/μmol for the solid yttrium coin production. ICP-MS analysis of the yttrium coin and the sputtered coins showed 99.99% yttrium removed with 178μg of yttrium in the final solution and 99.93-100% of yttrium removed with remaining range of 0-42μg of yttrium in the final solution, respectively. The specific activity calculated for the solid coin and 3 different sputtered coins using the concentration of Zr found via ICP-MS was 140±2mCi/μmol, 300±30mCi/μmol, 410±60mCi/μmol and 1719±5mCi/μmol, respectively. Labeling yields of the 89 Zr produced via sputtered targets for 89 Zr- DFO-trastuzumab were >98%. Overall, these results show the irradiation of yttrium sputtered niobium coins
Ahlgren, Eva-Christina; Fekry, Mostafa; Wiemann, Mathias; Söderberg, Christopher A.; Bernfur, Katja; Gakh, Olex; Rasmussen, Morten; Højrup, Peter; Emanuelsson, Cecilia; Isaya, Grazia
Patients suffering from the progressive neurodegenerative disease Friedreich’s ataxia have reduced expression levels of the protein frataxin. Three major isoforms of human frataxin have been identified, FXN42-210, FXN56-210 and FXN81-210, of which FXN81-210 is considered to be the mature form. Both long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks an N-terminal extension, has been shown to oligomerize in the presence of iron. To explore the mechanisms of stabilization of short variant frataxin oligomers we compare here the effect of iron on the oligomerization of CyaY and FXN81-210. Using dynamic light scattering, small-angle X-ray scattering, electron microscopy (EM) and cross linking mass spectrometry (MS), we show that at aerobic conditions in the presence of iron both FXN81-210 and CyaY form oligomers. However, while CyaY oligomers are stable over time, FXN81-210 oligomers are unstable and dissociate into monomers after about 24 h. EM and MS studies suggest that within the oligomers FXN81-210 and CyaY monomers are packed in a head-to-tail fashion in ring-shaped structures with potential iron-binding sites located at the interface between monomers. The higher stability of CyaY oligomers can be explained by a higher number of acidic residues at the interface between monomers, which may result in a more stable iron binding. We also show that CyaY oligomers may be dissociated by ferric iron chelators deferiprone and DFO, as well as by the ferrous iron chelator BIPY. Surprisingly, deferiprone and DFO stimulate FXN81-210 oligomerization, while BIPY does not show any effect on oligomerization in this case. The results suggest that FXN81-210 oligomerization is primarily driven by ferric iron, while both ferric and
Lu, Wenyi; Zhao, Mingfeng; Rajbhandary, Sajin; Xie, Fang; Chai, Xiao; Mu, Juan; Meng, Juanxia; Liu, Yongjun; Jiang, Yan; Xu, Xinnv; Meng, Aimin
Transfusional iron overload is of major concern in hematological disease. Iron-overload-related dyserythropoiesis and reactive oxygen species (ROS)-related damage to hematopoietic stem cell (HSC) function are major setbacks in treatment for such disorders. We therefore aim to investigate the effect of iron overload on hematopoiesis in the patients and explore the role of ROS in iron-induced oxidative damage in hematopoietic cells and microenvironment in vitro. The hematopoietic colony-forming capacity and ROS level of bone marrow cells were tested before and after iron chelation therapy. In vitro, we first established an iron overload model of bone marrow mononuclear cells (BMMNC) and umbilical cord-derived mesenchymal stem cells (UC-MSC). ROS level, cell cycle, and apoptosis were measured by FACS. Function of cells was individually studied by Colony-forming cell (CFC) assay and co-culture system. Finally, ROS-related signaling pathway was also detected by Western blot. After administering deferoxamine (DFO), reduced blood transfusion, increased neutrophil, increased platelet, and improved pancytopenia were observed in 76.9%, 46.2%, 26.9%, and 15.4% of the patients, respectively. Furthermore, the colony-forming capacity of BMMNC from iron overload patient was deficient, and ROS level was higher, which were partially recovered following iron chelation therapy. In vitro, exposure of BMMNC to ferric ammonium citrate (FAC) for 24 h decreased the ratio of CD34(+) cell from 0.91 ± 0.12% to 0.39 ± 0.07%. Excessive iron could also induce apoptosis, arrest cell cycle, and decrease function of BMMNC and UC-MSC, which was accompanied by increased ROS level and stimulated p38MAPK, p53 signaling pathway. More importantly, N-acetyl-L-cysteine (NAC) or DFO could partially attenuate cell injury and inhibit the signaling pathway induced by excessive iron. Our study shows that iron overload injures the hematopoiesis by damaging hematopoietic cell and hematopoietic
Song, Di Fei; Sommerville, Daniel; Brown, Adam G; Shimmon, Ronald G; Reedy, Brian J; Tahtouh, Mark
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
Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li
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
...The Small Communities Advisory Subcommittee (SCAS) will meet via teleconference on Tuesday, March 27, 2012, 2 p.m.-3 p.m. (ET), and the SCAS will meet at EPA's Region 8 office in Denver, CO, on Thursday, April 18, 2012, 3 p.m.-5 p.m. (MT). The Subcommittee will discuss decentralized wastewater treatment and other issues and recommendations to the Administrator regarding environmental issues affecting small communities. These are open meetings, and all interested persons are invited to participate. The Subcommittee will hear comments from the public during the teleconference on Tuesday, March 27, 2012 between 2:50 p.m. and 3 p.m. (ET) and during the meeting on Thursday, April 18, 2012 between 4:45 p.m. and 5 p.m. (MT). Individuals or organizations wishing to address the Subcommittee will be allowed a maximum of five minutes to present their point of view. Also, written comments should be submitted electronically to [email protected] Please contact the Designated Federal Officer (DFO) at the number listed below to schedule a time on the agenda. Time will be allotted on a first-come first-serve basis, and the total period for comments may be extended if the number of requests for appearances requires it. The Local Government Advisory Committee (LGAC) will meet at EPA's Region 8 office in Denver, CO, on Thursday, April 19, 2012, 10 a.m.- 4:15 p.m. (MT), and Friday, April 20, 2012, 9 a.m.-12 p.m. (MT). The Committee will discuss integrated water quality planning, hydraulic fracturing, air quality issues and environmental justice and Title VI. This is an open meeting and all interested persons are invited to participate. The Committee will hear comments from the public between 4 p.m.-4:15 p.m. (MT) on Thursday, April 19, 2012. Individuals or organizations wishing to address the Committee will be allowed a maximum of five minutes to present their point of view. Also, written comments should be submitted electronically to [email protected] Please contact the
Shah, A; Kumar, S; Simon, S D; Singh, D P; Kumar, A
HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several mechanisms including production of proinflammatory cytokines/chemokines and oxidative stress. Likewise, drug abuse is thought to have a direct impact on the pathology of HIV-associated neuroinflammation through the induction of proinflammatory cytokines/chemokines and oxidative stress. In the present study, we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen species (ROS) production in concentration- and time-dependent manners. The combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7±0.2- and 2.8±0.3-fold in SVGA and primary astrocytes, respectively) and protein (1.3±0.1-fold in SVGA and 1.4±0.03-fold in primary astrocytes) levels, suggesting the involvement of CYP2E1 in ROS production. This was further confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30–60%). As the CYP pathway is known to be coupled with the NOX pathway, including Fenton–Weiss–Haber (FWH) reaction, we examined whether the NOX pathway is also involved in ROS production induced by either gp120 or MA. Our results showed that selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction, deferoxamine (DFO), also significantly reduced ROS production. These findings were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase family). We then showed that gp120 and MA both induced apoptosis (caspase-3 activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting the involvement of CYP and NOX pathways in ROS
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)
Great diversity of the ionospheric phenomena leads to a variety of irregularity types with spatial size from many thousands of kilometers to few centimeters and lifetimes from days to fractions of second. Since the ionosphere strongly influences the propagation of radio waves, signal distortions caused by these irregularities affect short-wave transmissions on Earth, transiono-spheric satellite communications and navigation. In this work the solar wind and the equatorial ionosphere parameters, Kp, Dst, AU, AL indices characterized contribution of different mag-netospheric and ionospheric currents to the H-component of geomagnetic field are examined to test the space weather effect on the generation of ionospheric irregularities producing VLF scintillations. According to the results of the current statistical studies, one can predict scintil-lations from Aarons' criteria using the Dst index, which mainly depicts the magnetospheric ring current field. To amplify Aarons' criteria or to propose new criteria for predicting scintillation characteristics is the question. In the present phase of the experimental investigations of elec-tron density irregularities in the ionosphere new ways are opened up because observations in the interaction between the solar wind -magnetosphere -ionosphere during magnetic storms have progressed greatly. We have examined scintillation relation to magnetospheric and ionospheric currents and show that the factor, which presents during magnetic storms to fully inhibit scin-tillation, is the positive Bz-component of the IMF. During the positive Bz IMF F layer cannot raise altitude where scintillations are formed. The auroral indices and Kp do better for the prediction of the ionospheric scintillations at the equator. The interplanetary magnetic field data and models can be used to explain the relationship between the equatorial ionospheric parameters, h'F, foF2, and the equatorial geomagnetic variations with the polar ionosphere cur-rents and
Ratliff, S; Gustafson, B; Barry, K
The purpose of this work is to characterize the radiation-induced thermoluminescence properties of a dental restoration material and to see if the material might be feasible for use in retrospective radiation dosimetry. Retrospective, or accidental, dosimetry is the study of using nearby materials to measure radiation received by individuals. In this project we obtained samples of Ivoclar Vivadent e.max CAD material, a glass-ceramic used for making dental restorations such as full or partial crowns. The samples were machined into square chips .32 cm × .32 cm × .089 cm and annealed in the same furnace used by the dentist. The samples were exposed to a Cs-137 source using a PMMA source holder and then read in a Harshaw 3500 TLD reader. The samples were read without nitrogen gas flux using heating rates of 5 degrees C/s or 10 degrees C/s up to a maximum temperature of 400 degrees Celsius. The glow curves were analyzed using Systat PeakFIT peak-fitting software and Microsoft Excel spreadsheets. The authors gratefully thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN for the dental restoration materials and the use of their dental furnace. A sample subjected to a radiation exposure of .04 C/kg exhibits a glow curve with a prominent peak at approximately 140 degrees Celsius, which is well-modeled by the first order glow curve deconvolution formula developed by Kitis, Gomez-Ros, and Tuyn. The activation energy corresponding to this peak is approximately 1 eV. The thermoluminescent signal fades with time after exposure. Ivoclar Vivadent e.max CAD dental restoration material has the potential to be used as a material for retrospective Cs-137 radiation dosimetry. Future work could look at its thermoluminescent dosimetry properties in more detail and also at other dental restoration materials. The authors would like to thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN, for the donation of scrap dental restoration materials and
Spindler, Xanthe; Shimmon, Ronald; Roux, Claude; Lennard, Chris
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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Gao, Wei; Shen, Qiu; Zhou, Yuehua; Li, Xin
Floods are among the most expensive natural hazards experienced in many places of the world and can result in heavy losses of life and economic damages. The objective of this study is to analyze flood inundation in ungauged basins by performing near-real-time detection with flood extent and depth based on multi-source remote sensing data. Via spatial distribution analysis of flood extent and depth in a time series, the inundation condition and the characteristics of flood disaster can be reflected. The results show that the multi-source remote sensing data can make up the lack of hydrological data in ungauged basins, which is helpful to reconstruct hydrological sequence; the combination of MODIS (moderate-resolution imaging spectroradiometer) surface reflectance productions and the DFO (Dartmouth Flood Observatory) flood database can achieve the macro-dynamic monitoring of the flood inundation in ungauged basins, and then the differential technique of high-resolution optical and microwave images before and after floods can be used to calculate flood extent to reflect spatial changes of inundation; the monitoring algorithm for the flood depth combining RS and GIS is simple and easy and can quickly calculate the depth with a known flood extent that is obtained from remote sensing images in ungauged basins. Relevant results can provide effective help for the disaster relief work performed by government departments.
Chen, Bingcan; Rao, Jiajia; Ding, Yangping; McClements, David Julian; Decker, Eric Andrew
The impact of natural hydrophilic antioxidants, metal chelators, and hydrophilic antioxidant/metal chelator mixture on the oxidative stability of base algae oil and water-in-algae oil emulsion was investigated. The results showed that green tea extract and ascorbic acid had greatest protective effect against algae oil oxidation and generated four day lag phase, whereas rosmarinic acid, grape seed extract, grape seed extract polymer, deferoxamine (DFO), and ethylenediaminetetraacetic acid (EDTA) had no significant protective effect. Besides, there was no synergistic effect observed between natural antioxidants and ascorbic acid. The emulsifiers are critical to the physicochemical stability of water-in-algae oil emulsions. Polyglycerol polyricinoleate (PGPR) promoted the oxidation of emulsion. Conversely, the protective effect on algae oil oxidation was appreciated when defatted soybean lecithin (PC 75) or defatted lyso-lecithin (Lyso-PC) was added. The role of hydrophilic antioxidants in emulsion was similar to that in algae oil except EDTA which demonstrated strong antioxidative effect in emulsion. The results could provide information to build up stable food products containing polyunsaturated fatty acids (PUFA). Copyright © 2016 Elsevier Ltd. All rights reserved.
Porter, John B
The pathophysiological consequences of transfusional iron overload largely reflect the pattern of excess iron distribution and include cardiomyopathy, endocrinopathy, cirrhosis, and hepatocellular carcinoma. Since the introduction of desferrioxamine (DFO) in the late 1970s, these complications have fallen substantially but approximately half of the chelated adult patients with thalassemia major (TM) still show evidence of increased myocardial iron loading by MRI. An understanding of the factors that determine the propensity to extrahepatic iron distribution may be a key to minimizing the pathophysiological consequences of transfusional iron overload. Transfused patients with sickle cell disease (SCD) appear less likely to develop these extrahepatic complications, possibly because plasma nontransferrin-bound iron (NTBI) levels are typically lower than in TM patients at matched levels of iron loading. Other mechanisms that may reduce the extrahepatic iron distribution in SCD include raised plasma hepcidin due to chronic inflammation, lower growth differentiation factor 15 (GDF15) levels because of less ineffective erythropoiesis (IE), and induction of heme oxygenase (HO1) by intravascular hemolysis. Further understanding of these mechanisms may help in designing strategies to decrease extrahepatic iron distribution in TM.
Hoffbrand, A Victor; Taher, Ali; Cappellini, Maria Domenica
Patients with β-thalassemia major (TM) and other refractory anemias requiring regular blood transfusions accumulate iron that damages the liver, endocrine system, and most importantly the heart. The prognosis in TM has improved remarkably over the past 10 years. This improvement has resulted from the development of magnetic resonance imaging (MRI) techniques, especially T2*, to accurately measure cardiac and liver iron, and from the availability of 3 iron-chelating drugs. In this article we describe the use of MRI to determine which adult and pediatric patients need to begin iron chelation therapy and to monitor their progress. We summarize the properties of each of the 3 drugs, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), including their efficacy, patient acceptability, and side effects. We describe when to initiate or intensify therapy, switch to another drug, or use combined therapy. We also discuss the management of refractory anemias other than TM that may require multiple blood transfusions, including sickle cell anemia and myelodysplasia. The development of a potential fourth chelator FBS 0701 and the combined use of oral chelators may further improve the quality of life and survival in patients with TM and other transfusion-dependent patients.
Wang, Qiang; Luo, Wenjing; Zhang, Wenbin; Liu, Mingchao; Song, Haifeng; Chen, Jingyuan
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. Copyright © 2009 Elsevier Ltd. All rights reserved.
Porter, J.B.; Morgan, J.; Hoyes, K.P.
The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown bymore » a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).« less
Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang
Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.
Lipsky, B A; Peters, E J G; Senneville, E; Berendt, A R; Embil, J M; Lavery, L A; Urbančič-Rovan, V; Jeffcoate, W J
This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations. Copyright © 2012 John Wiley & Sons, Ltd.
Zarate-Reyes, Luis; Lopez-Pacheco, Cynthia; Nieto-Camacho, Antonio; Palacios, Eduardo; Gómez-Vidales, Virginia; Kaufhold, Stephan; Ufer, Kristian; García Zepeda, Eduardo; Cervini-Silva, Javiera
Antibiotic resistant bacteria persist throughout the world because they have evolved the ability to express various defense mechanisms to cope with antibiotics and the immune system; thus, low-cost strategies for the treatment of these bacteria are needed, such as the usage of environmental minerals. This paper reports the antimicrobial properties of a clay collected from Brunnenberg, Germany, that is composed of ferroan saponite with admixtures of quartz, feldspar and calcite as well as exposed or hidden (layered at inner regions) nano Fe(0). Based on the growth curves (log phase) of six antibiotic resistant bacteria (4 gram-negative and 2 gram-positive), we concluded that the clay acted as a bacteriostat; however, the clay was only active against the gram-negative bacteria (except for resilient Klebsiella pneumonia). The bacteriostatic mode of action was evidenced by the initial lack of Colony Forming Units on agar plates with growth registered afterward, certainly after 24h, and can be explained because interactions between membrane lipopolysaccharides and the siloxane surfaces of the clay. Labile or bioavailable Fe in the clay (extracted by EDTA or DFO-B) induced the quantitative production of HO as well as oxidative stress, which, nevertheless, did not account for by its bacteriostatic activity. Copyright © 2017 Elsevier B.V. All rights reserved.
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
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
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
Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A
We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.
Evangeli, Michael; Mughal, Kulsoom; Porter, John B
Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.
Woo, Seon Min; Seo, Seung Un; Min, Kyoung-Jin; Im, Seung-Soon; Nam, Ju-Ock; Chang, Jong-Soo; Kim, Shin; Park, Jong-Wook; Kwon, Taeg Kyu
Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor), necroptosis inhibitor (necrostatin-1), or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO)). Furthermore, corosolic acid significantly induces reactive oxygen species (ROS) levels, but antioxidants ( N -acetyl-l-cysteine (NAC) and trolox) do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498), breast cancer (MDA-MB231), and hepatocellular carcinoma (SK-Hep1 and Huh7) cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.
Mangle, Milery Figuera; Xu, Xioama; de Puit, M
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. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.
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.
Gosselin, Armand M.
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).
Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya
Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355
Asante, Kwabena O.; Arlan, Guleid A.; Pervez, Md Shahriar; Rowland, James
In many river basins around the world, inaccessibility of flow data is a major obstacle to water resource studies and operational monitoring. This paper describes a geospatial streamflow modeling system which is parameterized with global terrain, soils and land cover data and run operationally with satellite‐derived precipitation and evapotranspiration datasets. Simple linear methods transfer water through the subsurface, overland and river flow phases, and the resulting flows are expressed in terms of standard deviations from mean annual flow. In sample applications, the modeling system was used to simulate flow variations in the Congo, Niger, Nile, Zambezi, Orange and Lake Chad basins between 1998 and 2005, and the resulting flows were compared with mean monthly values from the open‐access Global River Discharge Database. While the uncalibrated model cannot predict the absolute magnitude of flow, it can quantify flow anomalies in terms of relative departures from mean flow. Most of the severe flood events identified in the flow anomalies were independently verified by the Dartmouth Flood Observatory (DFO) and the Emergency Disaster Database (EM‐DAT). Despite its limitations, the modeling system is valuable for rapid characterization of the relative magnitude of flood hazards and seasonal flow changes in data sparse settings.
This article examines the phenomenology of body shame in the context of the clinical encounter, using the television program 'Embarrassing Bodies' as illustrative. I will expand on the insights of Aaron Lazare's 1987 article 'Shame and Humiliation in the Medical Encounter' where it is argued that patients often see their diseases and ailments as defects, inadequacies or personal shortcomings and that visits to doctors and medical professionals involve potentially humiliating physical and psychological exposure. I will start by outlining a phenomenology of shame in order to understand more clearly the effect shame about the body can have in terms of one's personal experience and, furthermore, one's interpersonal dynamics. I will then examine shame in the clinical encounter, linking body shame to the cultural stigma attached to illness, dysfunction and bodily frailty. I will furthermore explore how shame can be exacerbated or even incited by physicians through judgment and as a result of the power imbalance inherent to the physician-patient dynamic, compounded by the contemporary tendency to moralise about 'lifestyle' illnesses. Lastly, I will provide some reflections for how health care workers might approach patient shame in clinical practice.
Meier Magistretti, Claudia; Downe, Soo; Lindstrøm, Bengt; Berg, Marie; Schwarz, Katharina Tritten
There is a lack of systematic evidence concerning health orientation in maternity practice in the current climate of risk avoidance. The midwifery professional project is orientated toward the preservation of normal physiological processes during the maternity episode. This study investigates accounts of midwives who were working in health-orientated birth settings, to examine if and how they frame a health orientation in professional practice. Twenty-seven narrative interviews were conducted with midwives working in pre-, peri-, and postnatal care in different maternity care settings in Switzerland, Austria, and Germany. In-depth and comparative pattern data analyses were conducted. The distinct practice orientation of the participants was revealed in three main concepts, underpinned by a common framework mirroring the three parameters of the Sense of Coherence (comprehensibility, manageability, and meaningfulness) described in Aaron Antonovsky's salutogenic theory. The midwives’ implicit salutogenic knowledge shaped their reported actions in supporting mothers, fathers, and families to have health-promoting experiences in maternity care. These results suggest that an implicit health orientation in maternity care practice can be prefered through examination of the practice reports of midwives working in settings that have a health-promoting philosophy. Implications for midwifery practice and research are discussed. Consideration is given to the relevance of the results for debates about avoiding overtreatment and for the operationalization of salutogenic theory in health care practice.
More than 2300 medical and scientific professionals attended the 4th Conference on Retroviruses and Opportunistic Infection held in Washington, DC, during January 22-26, 1997, to discuss the latest information on treatment for HIV/AIDS and opportunistic infections. The keynote speakers were Dr. David Ho, a researcher at the Aaron Diamond AIDS Institute, and Dr. Peter Piot, Director of UNAIDS. Dr. Ho told the audience that reasons exist to be hopeful about prolonging the life of people with AIDS even though HIV has not yet been eliminated from any infected individual. He urged the media to carefully and accurately portray HIV/AIDS, and stressed that there is no cure for AIDS and that safer sex practices should be maintained in order to prevent the sexual transmission of HIV. In his address, Dr. Piot considered how HIV/AIDS treatment and care options translate to the reality of developing countries in which 90% of all HIV/AIDS cases reside. Recognizing researchers' accomplishments in developing treatment therapies against HIV/AIDS, Piot urged them to focus upon the development of preventive technology, including microbicides, vaccines, and a way to prevent mother-to-fetus HIV transmission. Dr. Piot also discussed a proposed UNAIDS plan to make advanced therapies against HIV/AIDS available in developing countries.
Thin-film photovoltaic (PV) technologies led by CdTe and Cu(In,Ga) Se 2 (CIGS) are enjoying growing market share, due to their high performance and cost competitiveness, in the quest for renewable energy for the future. However the reliance on non-earth abundant elements tellurium and indium in these technologies presents a potential obstacle to ultimate terawatt deployment. We recently demonstrated kesterite Cu 2 ZnSn(Se,S)4 (CZTSSe) solar cells, comprised of the earth abundant metals copper, zinc and tin, with world record efficiency of 9.7%. In this talk we present a comprehensive device characterization study that pinpoints the key performance bottlenecks in these cells. We find strong buffer-absorber interface recombination and low minority carrier lifetimes that limit the open circuit voltage and a high and diverging device series resistance at lower temperature that suggests a blocking back contact that may limit the fill factor. These findings help to identify key areas for improvement for these CZTSSe cells in the pursuit of a high performance terawatt-scalable PV technology. In collaboration with Teodor K. Todorov, Aaron Barkhouse, Kejia Wang, David B. Mitzi, Supratik Guha, IBM T J Watson Research Center.
Dahlberg, E. Dan
The Physics Force is a very successful and entertaining outreach program of the Institute of Technology in the University of Minnesota developed to make science exciting and fun for students of all ages, from 6 to 106. Although all attendees, including high school and college students and guests from retirement homes, praise our performances, the primary focus is on K-6 students. The original Force consists of six k-12 teachers, Hank Ryan, Jon Barber, Jack Netland, Fred Orsted, Aaron Pinski, and Jay Dornfeld and Dan Dahlberg of the University of Minnesota Physics Department. The Force performed variations of The Physics Circus, our most popular show, at Disney's Epcot Center, parts of it were shown on Newton's Apple and several of us have performed demonstrations on the Knoff-Hoff Show, a very successful German T.V. science program. The goal of The Physics Force is to show students and the public Science is Fun, Science is Interesting, and Science is Understandable. By all measures we have available, we are extremely successful in reaching our goals. In the last three year cycle of our University support almost 100,000 residents of Minnesota (or about 2% of the total population) saw a Physics Force performance; it appears we will surpass those numbers in the present cycle.
Gleacher, Alissa A; Olin, Serene S; Nadeem, Erum; Pollock, Michele; Ringle, Vanesa; Bickman, Leonard; Douglas, Susan; Hoagwood, Kimberly
Measurement feedback systems (MFSs) have been proposed as a means of improving practice. The present study examined the implementation of a MFS, the Contextualized Feedback System (CFS), in two community-based clinic sites. Significant implementation differences across sites provided a basis for examining factors that influenced clinician uptake of CFS. Following the theoretical implementation framework of Aarons et al. (Adm Policy Mental Health Mental Health Serv Res 38(1):4-23, 2011), we coded qualitative data collected from eighteen clinicians (13 from Clinic U and 5 from Clinic R) who participated in semi-structured interviews about their experience with CFS implementation. Results suggest that clinicians at both clinics perceived more barriers than facilitators to CFS implementation. Interestingly, clinicians at the higher implementing clinic reported a higher proportion of barriers to facilitators (3:1 vs. 2:1); however, these clinicians also reported a significantly higher level of organizational and leadership supports for CFS implementation. Implications of these findings are discussed.
Ehrhart, Mark G; Torres, Elisa M; Wright, Lisa A; Martinez, Sandra Y; Aarons, Gregory A
There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. Copyright © 2015 Elsevier Ltd. All rights reserved.
PRO-140, a monoclonal antibody against the HIV coreceptor CCR5, is under investigation by Progenics and the Aaron Diamond AIDS Research Center (ADARC) as a potential treatment for HIV infection , , . Phase I/II trials were expected to commence during 2001 , , despite being initially planned for 2000 , , , , . In January 1998, ADARC and Progenics reported that the HIV binding site on the CCR5 coreceptor is distinct from betachemokine binding domains, which they claimed may allow for the development of therapeutics with fewer side effects , 421256]. In vitro studies have shown PRO-140 potently blocked all of 17 primary HIV isolates that use CCR5 as a fusion coreceptor . In October 2000, Progenics was awarded an SBIR grant to fund a 2-year project exploring the breadth, potency and durability of PRO-140 therapy in laboratory and animal models of HIV infection. This project was a collaboration between Progenics, Weill Medical College of Cornell University and the Scripps Research Institute . In May 1999, the company entered into an agreement with Protein Design Labs (PDL) for the humanization by PDL of PRO-140 . In November 1997, Progenics was awarded a 600,000 dollars grant from the NIAID for the examination of new approaches to HIV vaccine design based on CCR5 .
Research of non-equilibrium phase transitions of strongly correlated electrons is built around addressing an outstanding challenge: how to achieve ultrafast manipulation of competing magnetic/electronic phases and reveal thermodynamically hidden orders at highly non-thermal, femtosecond timescales? Recently we reveal a new paradigm called quantum femtosecond magnetism-photoinduced femtosecond magnetic phase transitions driven by quantum spin flip fluctuations correlated with laser-excited inter-atomic coherent bonding. We demonstrate an antiferromagnetic (AFM) to ferromagnetic (FM) switching during about 100 fs laser pulses in a colossal magneto-resistive manganese oxide. Our results show a huge photoinduced femtosecond spin generation, measured by magnetic circular dichroism, with photo-excitation threshold behavior absent in the picosecond dynamics. This reveals an initial quantum coherent regime of magnetism, while the optical polarization/coherence still interacts with the spins to initiate local FM correlations that compete with the surrounding AFM matrix. Our results thus provide a framework that explores quantum non-equilibrium kinetics to drive phase transitions between exotic ground states in strongly correlated elecrons, and raise fundamental questions regarding some accepted rules, such as free energy and adiabatic potential surface. This work is in collaboration with Tianqi Li, Aaron Patz, Leonidas Mouchliadis, Jiaqiang Yan, Thomas A. Lograsso, Ilias E. Perakis. This work was supported by the National Science Foundation (contract no. DMR-1055352). Material synthesis at the Ames Laboratory was supported by the US Department of Energy-Basic Energy Sciences (contract no. DE-AC02-7CH11358).
Delagrange, Philippe; Krause, Diana N.; Sugden, David; Cardinali, Daniel P.; Olcese, James
The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT1 and MT2, that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer. PMID:20605968
Ehrhart, Mark G.; Torres, Elisa M.; Wright, Lisa A.; Martinez, Sandra Y.; Aarons, Gregory A.
There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization’s climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. PMID:26563643
We are implementing a new platform for adiabatic quantum computation (AQC) based on trapped neutral atoms whose coupling is mediated by the dipole-dipole interactions of Rydberg states. Ground state cesium atoms are dressed by laser fields in a manner conditional on the Rydberg blockade mechanism,[3,4] thereby providing the requisite entangling interactions. As a benchmark we study a Quadratic Unconstrained Binary Optimization (QUBO) problem whose solution is found in the ground state spin configuration of an Ising-like model. In collaboration with Lambert Parazzoli, Sandia National Laboratories; Aaron Hankin, Center for Quantum Information and Control (CQuIC), University of New Mexico; James Chin-Wen Chou, Yuan-Yu Jau, Peter Schwindt, Cort Johnson, and George Burns, Sandia National Laboratories; Tyler Keating, Krittika Goyal, and Ivan Deutsch, Center for Quantum Information and Control (CQuIC), University of New Mexico; and Andrew Landahl, Sandia National Laboratories. This work was supported by the Laboratory Directed Research and Development program at Sandia National Laboratories
Becker, Craig M; Glascoff, Mary A; Felts, William Michael; Kent, Christopher
Although the western world is the most technologically advanced civilization to date, it is also the most addicted, obese, medicated, and in-debt adult population in history. Experts had predicted that the 21st century would be a time of better health and prosperity. Although wealth has increased, our quest to quell health problems using a pathogenic approach without understanding the interconnectedness of everyone and everything has damaged personal and planetary health. While current efforts help identify and eliminate causes of problems, they do not facilitate the creation of health and well-being as would be done with a salutogenic approach. Sociologist Aaron Antonovsky coined the term salutogenesis in 1979. It is derived from salus, which is Latin for health, and genesis, meaning to give birth. Salutogenesis, the study of the origins and creation of health, provides a method to identify an interconnected way to enhance well-being. Salutogenesis provides a framework for a method of practice to improve health promotion efforts. This article illustrates how quality management methods can be used to guide health promotion efforts focused on improving health beyond the absence of disease. Published by Elsevier Inc.
Cohler, Bertram J
Identity may be understood both as a life-story, either told or written as memoir or autobiography, and also as a practice such as producing or acting in gay pornographic film, but always within the context of social and historical change. Study of the memoirs of gay men who have been actors and/or producers of gay pornographic films across three generation cohorts provides an opportunity for understanding the interplay of social change and life circumstances in making gay identity. This perspective on identity is illustrated through the study of the memoirs of three men from different cohorts who have produced and acted in gay pornographic films: Wakefield Poole, born in 1936; Scott O'Hara, born in 1961; and Aaron Lawrence, born in 1971. Differences in style and content of both memoir and practice in gay pornographic films reflect changing social expectations regarding men who have sex with men following the emergence of the gay rights movement and the AIDS epidemic.
In the face of a growing public health concern accompanying the reemerging threat of preventable diseases, this research seeks mainly to explain variations in the perceived benefits and risks of vaccinations among the general public in the United States. As Mary Douglas and Aaron Wildavsky's grid-group cultural theory of risk perception claims, the analytical results based upon original data from a nationwide Internet survey of 1,213 American adults conducted in 2010 suggest that individuals' cultural predispositions contribute to the formation of their perceptions pertaining to vaccine benefits and risks at both societal and individual levels, in conjunction with other factors suggested by previous risk perception literature, such as perceived prevalence of diseases, trust, knowledge level, and demographic characteristics. Those with a strong hierarch orientation tend to envision greater benefits and lesser risks and conceive of a relatively high ratio of benefit to risk when compared to other cultural types. By contrast, those with a strong fatalist tendency are inclined to emphasize risks and downplay benefits while conceiving of a low vaccination benefit-risk ratio. Situated between hierarchs and fatalists, strong egalitarians are prone to perceive greater benefits, smaller risks, and a more positive benefit-risk ratio than strong individualists. © 2013 Society for Risk Analysis.
Gould, Laurence I.
Widespread (and seemingly dominant) claims about the dire consequences of anthropogenic global warming (AGW) have been propagated by both scientists and politicians and have been prominently featured by much of the mass media. This talk will examine some of those claims --- such as those made in the popular pro-AGW film, An Inconvenient Truth^1 --- from the perspectives of science^2 and scientific methodology^3. Some of the issues considered will be: What are the major ``greenhouse gases''? To what extent is global warming a result of human influences through an increase of ``greenhouse gases''? Is an increase in (1) global temperature and (2) carbon dioxide bad/good? What are some meanings that can be given to the term ``consensus'' in science? What are the estimated financial and other costs of governments implementing the Kyoto accords? Links to readings and videos will be given at the conclusion of the talk. ^1Gore, Al, An Inconvenient Truth: The Planetary Emergency of Global Warming and What We Can Do About It -- (Rodale Press, May, 2006). ^2Marlo Lewis, ``A Skeptic's Guide to An Inconvenient Truth'' http://www.cei.org/pages/aitresponse-book.cfm ^3Aaron Wildavsky, But Is It True? A Citizen's Guide to Environmental Health and Safety Issues (Harvard University Press, 1995), Intro. and Chap. 11. To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.C1.6
The Bilbao statement was the result of a work meeting, held the day before the closing session by a group of representative experts, formed by general chairmen and meeting organizers. The compelled and necessary consent gave rise to the document that was read and communicated to the world's public opinion during the closing act on may 26, 1993. Notwithstanding, the working group considered that the divulged version was provisory and committed to continue the task of re-elaborating the statement. The aim was to complete and improve it, taking the greatest advantage of the important meeting achievements. The document that is next reproduced is the definitive integral version of the Bilbao Statement. The expert group that takes the responsibility of this Statement is Jean Dausset, Nobel Prize of Medicine (1980); Carleton Gajdusek, Nobel Prize of Medicine (1976); Santiago Grisolía president of UNESCO committee for the Genome Project; Michael Kirby, President of the Court of Appeal of the Supreme Court of New South Wales, Australia; Aaron Klug, member of the Constitutional Council, Paris, France; Rafael Mendizábal, Judge of the Constitutional Court, Madrid, Spain; Juan Bautista Pardo, President of the Superior Court of Justice of the Basque Country and Carlos María Romeo Casabona, Director of the Chair of Law and Human Genome of the University of Deusto (Bilbao).
Coherent manipulation of spin-like quantum numbers facilitates the development of new quantum technologies. Layered transition metal dichalcogenides provide an ideal laboratory to exploit such dynamic control of spin, pseudospin, and their interplay. Here, we discuss two examples based on monolayer and bilayer WSe2. Due to the inversion asymmetry in monolayer WSe2, valley pseudospins, which index the degenerate extrema of the energy-momentum bands, possess circularly polarized optical selection rules. In addition to the generation of valley polarization through optical pumping of valley excitons, we demonstrate the creation of a coherent superposition between valley states in monolayer WSe2 by linearly polarized excitation. On the other hand, bilayer WSe2 provides an additional quantum degree of freedom, the layer pseudospin, which corresponds to layer polarization. In AB stacked bilayers, we find the real spin is locked to layer pseudospin for a given valley, which results in the suppression of spin relaxation and electrical control of spin Zeeman splitting without an applied magnetic field. Additionally, we obtain spectroscopic evidence of interlayer and intralayer trion species, an important step toward coherent optical control in van der Waals 2D heterostructures. Aaron Jones partially supported by NSF Grant No. DGE-0718124.
Tucker, J Allan; DeGroft, Aaron H
At the Ultrapath X meeting in Florence, the regular session opened with a presentation of Aaron DeGroft's engrossing story of investigating the authenticity of a portrait of Federico II Gonzaga, Duke of Mantua. In the early 1900s, this work had been deemed to be an authentic production by Titian, a great artist of the Italian Renaissance. A respected art historian, however, discovered a conflict of dates that led to the conclusion that this work was not authentic. In a process sometimes analogous to the practice of surgical pathology, Dr. DeGroft pursued a review of the original materials that refutes this seeming contradiction of dates. Dr. DeGroft also undertook an extensive art historical examination and scientific analysis, including the use of electron microscopy, to persuasively conclude that this portrait is authentic. Further, his work provided a bridge from the conference setting in Florence, rich in Renaissance art, to the contemporary update on ultrastructural pathology provided by the conference.
Fillo, Aaron; Niemeyer, Kyle
Teaching scientific research topics to K-12 audiences in an engaging and meaningful way does not need to be hard; with the right insight and techniques it can be fun to encourage self-guided STEAM (science, technology, engineering, arts, and mathematics) exploration. LIB LAB, short for Library Laboratory, is an educational video series produced by Aaron J. Fillo at Oregon State University in partnership with the Corvallis-Benton County Public Library targeted at K-12 students. Each episode explores a variety of scientific fundamentals with playful experiments and demonstrations. The video lessons are developed using evidence-based practices such as dispelling misconceptions, and language immersion. Each video includes directions for a related experiment that young viewers can conduct at home. In addition, science kits for these at-home experiments are distributed for free to students through the public library network in Benton County, Oregon. This talk will focus on the development of multimedia science education tools and several techniques that scientists can use to engage with a broad audience more effectively. Using examples from the LIB LAB YouTube Channel and collection of hands-on science demonstrations and take-home kits, this talk will present STEAM education in action. Corvallis-Benton County Public Library.
Rosen, C S; Matthieu, M M; Wiltsey Stirman, S; Cook, J M; Landes, S; Bernardy, N C; Chard, K M; Crowley, J; Eftekhari, A; Finley, E P; Hamblen, J L; Harik, J M; Kehle-Forbes, S M; Meis, L A; Osei-Bonsu, P E; Rodriguez, A L; Ruggiero, K J; Ruzek, J I; Smith, B N; Trent, L; Watts, B V
Since 2006, the Veterans Health Administration (VHA) has instituted policy changes and training programs to support system-wide implementation of two evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). To assess lessons learned from this unprecedented effort, we used PubMed and the PILOTS databases and networking with researchers to identify 32 reports on contextual influences on implementation or sustainment of EBPs for PTSD in VHA settings. Findings were initially organized using the exploration, planning, implementation, and sustainment framework (EPIS; Aarons et al. in Adm Policy Ment Health Health Serv Res 38:4-23, 2011). Results that could not be adequately captured within the EPIS framework, such as implementation outcomes and adopter beliefs about the innovation, were coded using constructs from the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework (Glasgow et al. in Am J Public Health 89:1322-1327, 1999) and Consolidated Framework for Implementation Research (CFIR; Damschroder et al. in Implement Sci 4(1):50, 2009). We highlight key areas of progress in implementation, identify continuing challenges and research questions, and discuss implications for future efforts to promote EBPs in large health care systems.
Binder, Heinz P.; Mesenholl-Strehler, Elke; Paß, Paul; Endler, P. Christian
The sense of coherence (according Aaron Antonovsky, 1923—1994, when a persons sense that his/her own life and the world are sufficiently comprehensible, manageable, and meaningful) of Austrian psychotherapists was assessed and compared with a standard sample, as well as with the sense of coherence (SOC) of members of other professions. In addition, the question as to whether psychotherapists who had completed more extensive individual training therapy/self-awareness sessions had a higher SOC than do those with fewer, was addressed. Forty psychotherapists who worked in private practices and various psychosocial health care institutions in Styria, Austria took part in the study. The investigation was conducted in the form of a questionnaire assessment. The evaluation showed that the overall SOC value of the professional group in question was significantly higher than that of the standard sample (162.3 vs. 145.7), as well as other samples (physicians: SOC = 153.8; teachers: SOC = 156.1; physiotherapists SOC = 158.1). Concerning whether psychotherapists who had completed more individual training therapy/self-awareness sessions had higher SOC values than did those with fewer, we found no difference in regard to the overall SOC score or SOC scores for individual components. The SOC of psychotherapists did not seem to depend on the number of additional training therapy/self-awareness sessions. PMID:17370015
Poradowska-Trzos, Magdalena; Dudek, Dominika; Rogoz, Monika; Zieba, Andrzej
According to Aaron Beck, dysfunctional thinking patterns appear also in euthymic patients, after withdrawal of acute diseases symptoms. Patients have a disordered, negative image of themselves, of their future and the surrounding world. It has been shown that a way a man perceives possessed social support has a basic meaning for him. The purpose of the research was to analyze the relationship between perceived social support and the patient's cognitive style. The study group consisted of euthymic outpatients diagnosed with recurrent depressive disorder (UID) or bipolar affective disorder (BID). Assessment of a cognitive style was made according to the Rosenberg Scale, Hopelessness Scale HS-20 and Automatique Thoughts Questionnaire ATQ 30, assessment of the amount of received support - according to Cohen's ISEL. The presented study revealed that, in both groups of patients, a thinking style is disturbed and that there is a link between a cognitive style and the perception of the level of received support. The link was stronger in the group of patients with unipolar affective disorder. In both groups, correlations concerning emotional support were the highest.
White, D; Stowell, M; Koning, J
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, andmore » 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.« less
Arnold, R.G.; Baygents, J.C.; Ogden, K.L.
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. Copiesmore » 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.« less
In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a mission science briefing for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Sean Potter of NASA Communications; Dr. Chris Ruf, CYGNSS principal investigator, Department of Climate and Space Sciences and Engineering at the University of Michigan; Aaron Ridley, CYGNSS constellation scientist in the Climate and Space Department at the University of Michigan in Ann Arbor, Michigan; and Mary Morris, doctoral student in the Department of Climate and Space Sciences and Engineering at the University of Michigan. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.
Olswang, Lesley B.; Greenslade, Kathryn; Pinder, Gay Lloyd; Dowden, Patricia; Madden, Jodi
Purpose This research investigated a first step in implementing the dynamic assessment (DA) component of Triadic Gaze Intervention (Olswang, Feuerstein, Pinder, & Dowden, 2013; Olswang et al., 2014), an evidence-based protocol for teaching early signals of communication to young children with physical disabilities. Clinician attitudes about adopting external evidence into practice and implementation fidelity in DA protocol delivery were examined following training. Method Seven early intervention clinicians from multiple disciplines were trained to deliver the four essential elements of the DA protocol: (a) provide communication opportunity, (b) recognize child's potentially communicative signal, (c) shape child's signal toward triadic gaze, and (d) reinforce with play. Clinician attitude regarding adopting evidence into practice was measured at baseline and follow-up, with the Evidence-Based Practice Attitude Scale (Aarons, 2004). Implementation fidelity in delivering the protocol was measured for adherence (accuracy) and competence (quality) during trial implementation. Results Clinicians' attitudes about trying new evidence that at first was perceived as incongruent with their practice improved over the course of the research. Clinicians demonstrated strong adherence to the DA protocol; however, competence varied across clinicians and appeared related to child performance. Conclusions The results provided insight into moving Triadic Gaze Intervention into practice and yielded valuable information regarding the implementation process, with implications for future research. PMID:28525577
Tsionou, Maria Iris; Knapp, Caroline E; Foley, Calum A; Munteanu, Catherine R; Cakebread, Andrew; Imberti, Cinzia; Eykyn, Thomas R; Young, Jennifer D; Paterson, Brett M; Blower, Philip J; Ma, Michelle T
Gallium-68 ( 68 Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68 Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68 Ga 3+ . Ideally, the chelator will rapidly, quantitatively and stably coordinate 68 Ga 3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68 Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68 Ga 3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68 Ga 3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5-50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68 Ga 3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low
Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism.
Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos
Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster wild type Canton-S acutely or chronically treated with paraquat (PQ), a selective toxin for elimination of dopaminergic (DAergic) neurons by oxidative stress (OS), as model of Parkinson's disease (PD). This study reports for the first time that knock-down (K-D) parkin Drosophila melanogaster (TH-GAL4; UAS-RNAi-parkin) chronically exposed to PQ (0.1-0.25 mM), FeSO(4) (Fe, 0.1mM), deferoxamine (DFO, 0.01 mM) alone or (0.1mM) PQ in combination with polyphenols propyl gallate (PG, 0.1mM) and epigallocathecin gallate (EGCG, 0.1, 0.5mM) showed significantly higher life span and locomotor activity than untreated K-D flies or treated with (1, 5, 20mM) PQ alone. Whilst gallic acid (GA, 0.1, 0.5mM) alone or in the presence of PQ provoked no effect on K-D flies, epicathecin (EC, 0.5mM) only showed a positive effect on prolonging K-D flies' life span. It is shown that PG (and EGCG) protected protocerebral posterolateral 1 (PPL1) DAergic neurons against PQ. Interestingly, the protective effect of low PQ concentrations, DFO and iron might be explained by a phenomenon known as "hormesis." However, pre-fed K-D flies with (0.1mM) PQ for 7 days and then exposed to (0.25 mM) for additional 8 days affect neither survival nor climbing of K-D Drosophila compared to flies treated with (0.25 mM) PQ alone. Remarkably, K-D flies treated with 0.1mM PQ (7 days) and then with (0.25 mM) PQ plus PG (8 days) behaved almost as flies treated with (0.25 mM) PQ. Taken these data suggest that antioxidant supplements that synergistically act with low pro-oxidant stimuli to prolong and increase locomotor activity become inefficient once a threshold of OS has been reached in K-D flies. Our present findings support the notion that genetically altered Drosophila melanogaster as suitable model to study genetic and environmental factors as causal and/or modulators in the development of autosomal
Geroldinger, Gerald; Tonner, Matthias; Hettegger, Hubert; Bacher, Markus; Monzote, Lianet; Walter, Martin; Staniek, Katrin; Rosenau, Thomas; Gille, Lars
Endoperoxides (EP) are an emerging class of drugs which have potential in antiparasitic therapy, but also in other fields. For malaria therapy the EP artemisinin (Art) and its derivatives are successfully used. We have shown in the past that the EP ascaridole (Asc) is useful for the treatment of cutaneous leishmaniasis in a mouse model. Biomimetic experiments suggested that these drugs need activation in the respective target pathogens to exert their function. In spite of this idea, direct activation of EP to radicals inside cells has never been demonstrated. Therefore, this study was initiated to explore the activation of Asc in biomimetic systems and inside Leishmania in comparison to Art. Using electron paramagnetic resonance spectroscopy (EPR) in combination with spin-trapping we identified the secondary alkyl radical intermediates arising from reduction by Fe 2+ in cell-free systems. Combined GC/NMR analysis confirmed the loss of isopropyl residues from Asc during this process as intermediates. This activation of Asc was stimulated by low molecular Fe 2+ complexes or alternatively by hemin in conjunction with thiol reductants, such as cysteine (Cys). In Leishmania tarentolae promastigotes (LtP) as model for pathogenic forms of Leishmania carbon-centered radicals were identified in the presence of Asc by EPR spin-trapping. Both Asc and Art inhibited the viability in LtP with IC 50 values in the low micromolar range while IC 50 values for J774 macrophages were considerably higher. A similar structure without EP bridge (1,4-cineole) resulted in no detectable radicals and possessed much less cytotoxicity in LtP and no selectivity for LtP compared to J774 cells. The Asc-derived radical formation in LtP was inhibited by the iron chelator deferoxamine (DFO), and stimulated by Cys (a suitable reductant for hemin). The IC 50 values for LtP viability in the presence of Asc or Art were increased significantly by the spin trap DMPO, while Cys and DFO increased only IC 50
Shen, X.; Lazin, R.; Anagnostou, E. N.; Wanik, D. W.; Brakenridge, G. R.
Synthetic Aperture Radar (SAR) observations is the only reliable remote sensing data source to map flood inundation during severe weather events. Unfortunately, since state-of-art data processing algorithms cannot meet the automation and quality standard of a near-real-time (NRT) system, quality controlled inundation mapping by SAR currently depends heavily on manual processing, which limits our capability to quickly issue flood inundation maps at global scale. Specifically, most SAR-based inundation mapping algorithms are not fully automated, while those that are automated exhibit severe over- and/or under-detection errors that limit their potential. These detection errors are primarily caused by the strong overlap among the SAR backscattering probability density functions (PDF) of different land cover types. In this study, we tested a newly developed NRT SAR-based inundation mapping system, named Radar Produced Inundation Diary (RAPID), using Sentinel-1 dual polarized SAR data over recent flood events caused by Hurricanes Harvey, Irma, and Maria (2017). The system consists of 1) self-optimized multi-threshold classification, 2) over-detection removal using land-cover information and change detection, 3) under-detection compensation, and 4) machine-learning based correction. Algorithm details are introduced in another poster, H53J-1603. Good agreements were obtained by comparing the result from RAPID with visual interpretation of SAR images and manual processing from Dartmouth Flood Observatory (DFO) (See Figure 1). Specifically, the over- and under-detections that is typically noted in automated methods is significantly reduced to negligible levels. This performance indicates that RAPID can address the automation and accuracy issues of current state-of-art algorithms and has the potential to apply operationally on a number of satellite SAR missions, such as SWOT, ALOS, Sentinel etc. RAPID data can support many applications such as rapid assessment of damage
Frasson, R. P. M.; Schumann, G.
The SWOT mission will measure river width and water surface elevations of rivers wider than 100 m. As the data gathered by this mission will be freely available, it can be of great use for flood modeling, especially in areas where streamgage networks are exceedingly sparse, or when data sharing barriers prevent the timely access to information. Despite having world-wide coverage, SWOT's temporal sampling is limited, with most locations being revisited once or twice every 21 days. Our objective is to evaluate which fraction of world-wide floods SWOT will observe and how many observations per event the satellite will likely obtain. We take advantage of the extensive database of floods constructed by the Dartmouth Flood Observatory, who, since 1985, searches through news sources and governmental agencies, and more recently remote sensing imagery for flood information, including flood duration, location and affected area. We cross-referenced the flood locations in the DFO archive with the SWOT prototype prior database of river centerlines and the anticipated satellite's orbit to identify how many of the SWOT swaths were located within 10 km, 20 km, and 50 km from a flood centroid. Subsequently, we estimated the probability that SWOT would have at least one observation of a flood event per distance bin by multiplying the number of swaths in the distance bin by the flood duration divided by the SWOT orbit repeat period. Our analysis contemplated 132 world-wide floods recorded between May 2016 and May 2017. From these, 29, 52, and 86 floods had at least a 50% probability of having one overpass within 10 km, 20 km, and 50 km respectively. Moreover, after excluding flood events with no river centerlines within 10 km of its centroid, the average number of swaths within 10 km of a flood centroid was 1.79, indicating that in the 37 flood events that were likely caused by river flooding, at least one measurement was guaranteed to happen during the event.
Xu, Qin-Qin; Qinghai Provincial People's Hospital, Xining; Xiao, Feng-Jun
Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1more » inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. - Highlights: • Hypoxia induces upregulation of HIF-1α, HIF-2α and Ptpmt1; HIF-2a induces Ptpmt1 upregulation in TF-1 cells. • PTPMT-1 inhibition reduces growth and induces apoptosis of TF-1 cells. • PTPMT1 inhibition downregulates Glut-1, Glut-3 expression and reduces glucose consumption.« less
Jang, U. G.; Kang, S. G.; Hong, J. K.; Jin, Y. K.; Dallimore, S.; Riedel, M.; Paull, C. K.
2014 Expedition ARA05C was a multidisciplinary undertaking conducted in the Canadian Beaufort Sea, Arctic Ocean on the Korean ice breaker IBRV ARAON from August 30 to September 19, 2014. The program was carried out as collaboration between the Korea Polar Research Institute (KOPRI), Geological Survey of Canada (GSC), Monterey Bay Aquarium Research Institute (MBARI), Department of Fisheries and Ocean (DFO) with participation by Bremen University (BARUM). During this expedition, multi-channel seismic (MCS) data were acquired on the outer continental shelf and upper slope of the Canadian Beaufort Sea, totaling 20 lines with 1,000 line-kilometers from September 1 to September 13, 2014. Three MCS survey lines was designed to cross the three submarine mud volcanoes found in the slope at approximate water depth of 290 m, 460 m and 740 m. Submarine mud volcanoes are seafloor structures with positive topography formed by a combination of mud eruption, gas emission, and water seepage from the subsurface. MCS data will allow image subsurface structures of mud volcanoes as identification of fluid migration pathways, however, imaging its subsurface structure is difficult by using conventional seismic data processing procedure, because it is seismically characterized by acoustically transparent facies. Full waveform inversion (FWI) is non-linear data-fitting procedure to estimate the physical properties of the subsurface by minimizing the difference between the observed and modelled data. FWI uses the two-wave wave equation to compute forward/backward wavefield to calculate the gradient direction, therefore it can derive more detailed velocity model beyond travel-time tomography techniques, which use only the kinematics of seismic data, by additional information provided by the amplitude and phase of the seismic waveform. In this study, we suggest P-wave structure of mud volcanos, which were inverted by 2D acoustic FWI. It will be useful to understand the characterization of mud
A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload.
Sripetchwandee, Jirapas; Wongjaikam, Suwakon; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C
Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy. Male Wistar rats (n=42) were assigned to receive a normal diet (ND) or a high-iron diet (HFe) for 4months. At the 2nd month, HFe-fed rats were treated with a vehicle, deferoxamine (DFO), DFP, deferasirox (DFX), n-acetyl cysteine (NAC) or a combination of DFP with NAC, while ND-fed rats received vehicle. At the end of the experiment, rats were decapitated and brains were removed to determine brain iron level and deposition, brain mitochondrial function, BBB protein expression, brain mitochondrial dynamic, brain apoptosis, tau-hyperphosphorylation, amyloid-β (Aβ) accumulation and dendritic spine density. The results showed that iron-overload induced BBB breakdown, brain iron accumulation, brain mitochondrial dysfunction, impaired brain mitochondrial dynamics, tau-hyperphosphorylation, Aβ accumulation and dendritic spine reduction. All treatments, except DFX, attenuated these impairments. Moreover, combined therapy provided a greater efficacy than monotherapy. These findings suggested that iron-overload induced brain iron toxicity and a combination of an iron chelator with an antioxidant provided a greatest efficacy for neuroprotection than monotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana
To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.
Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana
Background To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. Methods A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Results Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. Conclusion A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL. PMID:17007645
De Bortoli, Maida; Taverna, Elena; Maffioli, Elisa; Casalini, Patrizia; Crisafi, Francesco; Kumar, Vikas; Caccia, Claudio; Polli, Dario; Tedeschi, Gabriella; Bongarzone, Italia
Current insights into the effects of iron deficiency in tumour cells are not commensurate with the importance of iron in cell metabolism. Studies have predominantly focused on the effects of oxygen or glucose scarcity in tumour cells, while attributing insufficient emphasis to the inadequate supply of iron in hypoxic regions. Cellular responses to iron deficiency and hypoxia are interlinked and may strongly affect tumour metabolism. We examined the morphological, proteomic, and metabolic effects induced by two iron chelators-deferoxamine (DFO) and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT)-on MDA-MB-231 and MDA-MB-157 breast cancer cells. These chelators induced a cytoplasmic massive vacuolation and accumulation of lipid droplets (LDs), eventually followed by implosive, non-autophagic, and non-apoptotic death similar to methuosis. Vacuoles and LDs are generated by expansion of the endoplasmic reticulum (ER) based on extracellular fluid import, which includes unsaturated fatty acids that accumulate in LDs. Typical physiological phenomena associated with hypoxia are observed, such as inhibition of translation, mitochondrial dysfunction, and metabolic remodelling. These survival-oriented changes are associated with a greater expression of epithelial/mesenchymal transcription markers. Iron starvation induces a hypoxia-like program able to scavenge nutrients from the extracellular environment, and cells assume a hypertrophic phenotype. Such survival strategy is accompanied by the ER-dependent massive cytoplasmic vacuolization, mitochondrial dysfunctions, and LD accumulation and then evolves into cell death. LDs containing a greater proportion of unsaturated lipids are released as a consequence of cell death. The consequence of the disruption of iron metabolism in tumour tissue and the effects of LDs on intercellular communication, cancer-inflammation axis, and immunity remain to be explored. Considering the potential benefits, these are crucial
Benkaddour, Asmae; Bahije, Loubna; Bahoum, Asmae; Zaoui, Fatima
The appearance of white spots on the vestibular surface of teeth fitted with brackets has been described as one of the potential iatrogenic effects of orthodontic treatment. These enamel demineralizations, more commonly known as "white spot lesions" (WSL), lead in some rare cases to the creation of true cavities, causing both esthetic and functional problems. The aim of our retrospective clinical study was to evaluate the incidence of the appearance of these WSL in a Moroccan orthodontic population and to determine possible associations with a number of risk factors. The study was based on intraoral photographs of a pool of 69 patients who underwent orthodontic treatment with or without extractions in the DFO unit of the Rabat CCDT (Center for dental consultation and treatment). Patients with prostheses or WSL before the beginning of the study were excluded. Digital start- and end-of-treatment photos for each patient were compared by a single operator looking for the appearance of WSL on the vestibular surfaces of the incisors, canines, premolars and first molars. WSL were classed according to three degrees of severity: slight, severe and cavitation. Data were processed using SPSS 13.0 software. The results of the study showed that the prevalence of WSL in the sample was 66.7%, with a highly significant predominance of localization in the premolar/molar segment and in patients with poor oral hygiene. Poor oral and dental hygiene was identified as the most important risk factor for the development of white spots during multibracket orthodontic treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Cameron, Delroy; Bodenreider, Olivier; Yalamanchili, Hima; Danh, Tu; Vallabhaneni, Sreeram; Thirunarayan, Krishnaprasad; Sheth, Amit P.; Rindflesch, Thomas C.
Objectives This paper presents a methodology for recovering and decomposing Swanson’s Raynaud Syndrome–Fish Oil Hypothesis semi-automatically. The methodology leverages the semantics of assertions extracted from biomedical literature (called semantic predications) along with structured background knowledge and graph-based algorithms to semi-automatically capture the informative associations originally discovered manually by Swanson. Demonstrating that Swanson’s manually intensive techniques can be undertaken semi-automatically, paves the way for fully automatic semantics-based hypothesis generation from scientific literature. Methods Semantic predications obtained from biomedical literature allow the construction of labeled directed graphs which contain various associations among concepts from the literature. By aggregating such associations into informative subgraphs, some of the relevant details originally articulated by Swanson has been uncovered. However, by leveraging background knowledge to bridge important knowledge gaps in the literature, a methodology for semi-automatically capturing the detailed associations originally explicated in natural language by Swanson has been developed. Results Our methodology not only recovered the 3 associations commonly recognized as Swanson’s Hypothesis, but also decomposed them into an additional 16 detailed associations, formulated as chains of semantic predications. Altogether, 14 out of the 19 associations that can be attributed to Swanson were retrieved using our approach. To the best of our knowledge, such an in-depth recovery and decomposition of Swanson’s Hypothesis has never been attempted. Conclusion In this work therefore, we presented a methodology for semi- automatically recovering and decomposing Swanson’s RS-DFO Hypothesis using semantic representations and graph algorithms. Our methodology provides new insights into potential prerequisites for semantics-driven Literature-Based Discovery (LBD
Faucher, M.; Roy, F.; Desjardins, S.; Fogarty, C.; Pellerin, P.; Ritchie, H.; Denis, B.
A fully interactive coupled atmosphere-ocean-ice forecasting system for the Gulf of St. Lawrence (GSL) has been running in experimental mode at the Canadian Meteorological Centre (CMC) for the last two winter seasons. The goal of this project is to provide more accurate weather and sea ice forecasts over the GSL and adjacent coastal areas by including atmosphere-oceanice interactions in the CMC operational forecast system using a formal coupling strategy between two independent modeling components. The atmospheric component is the Canadian operational GEM model (Côté et al. 1998) and the oceanic component is the ocean-ice model for the Gulf of St. Lawrence developed at the Maurice Lamontagne Institute (IML) (Saucier et al. 2003, 2004). The coupling between those two models is achieved by exchanging surface fluxes and variables through MPI communication. The re-gridding of the variables is done with a package developed at the Recherche en Prevision Numerique centre (RPN, Canada). Coupled atmosphere - ocean - ice forecasts are issued once a day based on 00GMT data. Results for the past two years have demonstrated that the coupled system produces improved forecasts in and around the GSL during all seasons, proving that atmosphere-ocean-ice interactions are indeed important even for short-term Canadian weather forecasts. This has important implications for other coupled modeling and data assimilation partnerships that are in progress involving EC, the Department of Fisheries and Oceans (DFO) and the National Defense (DND). Following this experimental phase, it is anticipated that this GSL system will be the first fully interactive coupled system to be implemented at CMC.