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Sample records for aaas philip hauge

  1. Lifetime achievement

    Science.gov (United States)

    Carlowicz, Michael

    The American Association for the Advancement of Science (AAAS) is accepting nominations for the 1996 Philip Hauge Abelson Prize. The prize is awarded annually to either a public servant who has made sustained contributions to the advancement of science or to scientists who have distinguished themselves for both the quality of their work and their leadership in the scientific community.

  2. Kiik ja riik / Toomas Haug

    Index Scriptorium Estoniae

    Haug, Toomas, 1956-

    1996-01-01

    Arvustus: Kiik, Heino. Murrang. (Aasta 1986). Tln. : Õllu, 1995 ; Kiik, Heino. Fataalne optimist. (Aasta 1987). Tln. : Õllu, 1995. Ilmunud ka kogumikus: Haug, Toomas. Troojamäe tõotus. Tallinn : Eesti Keele Sihtasutus, 2004, lk. 353-357

  3. Jens Haug keelab oma lastel majandust õppida / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2006-01-01

    Endine ärimees Jens Haug õpib ülikoolis semiootikat ja töötab majandus- ja kommunikatsiooniministeeriumis kriisireguleerimise osakonnas. Vt. samas: Kolleeg hindab Jens Haugi teravat mõistust; Karjäär

  4. Philips Pavilion

    NARCIS (Netherlands)

    Konig dos Santos, M.M.

    2012-01-01

    The Philips company street name meant Light and Sound and they wished to show what Man can do. Therefore for the Expo'58 in Brussels they contracted Le Corbusier to create a pavilion that would transmit their message as well as show what Philips is. After all, the main aim of the 1958 exhibition was

  5. Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

    Science.gov (United States)

    van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

    2017-04-01

    Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

  6. Abdominal Aortic Aneurysm (AAA)

    Science.gov (United States)

    ... Professions Site Index A-Z Abdominal Aortic Aneurysm (AAA) Abdominal aortic aneurysm (AAA) occurs when atherosclerosis or plaque buildup causes the ... weak and bulge outward like a balloon. An AAA develops slowly over time and has few noticeable ...

  7. AAA Foundation for Traffic Safety

    Science.gov (United States)

    ... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

  8. AAA-ATPases in Protein Degradation

    Directory of Open Access Journals (Sweden)

    Ravikiran S. Yedidi

    2017-06-01

    Full Text Available Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

  9. AAA-ATPases in Protein Degradation.

    Science.gov (United States)

    Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

    2017-01-01

    Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

  10. LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

    Science.gov (United States)

    Chenait, Manel

    Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

  11. A Fan Solution for the Philips Airfryer

    OpenAIRE

    Gibernau Torres, Octavi

    2012-01-01

    The thesis on hand has been carried out at Philips Consumer Lifestyle Drachten that, together with Delft University of Technology, aims to develop a computed tool that determines the performance and efficiency curve of any centrifugal fan operating in the Philips Airfryer. The Airfryer is a Philips kitchen appliance that, thanks to the use of Rapid Air Technology, enables to fry food with a reduction of unhealthy fat up to 80%. Philips aims at reducing the total cost of the cooking fan an...

  12. AAA - University Fellowship Program for 2001: Process, Progress and Prospects (Report on the Solicitation and Award of AAA-UFP Fellowships)

    International Nuclear Information System (INIS)

    Davis, Freddie; Dixon, Cathy

    2002-01-01

    The AAA University Fellowship Program (AAA-UFP) was developed by the Amarillo National Research Center (ANRC) in fiscal year 2001 for The Department of Energy, Office of Nuclear Energy, Science, and Technology (NE), Office of Advanced Accelerator Applications (AAA). The AAA-UFP provides financial support for science and engineering students to pursue master's degrees in areas that support the AAA Program. Each fellow's thesis research must relate to the AAA program and must be approved by the Department of Energy. ANRC manages the AAA-UFP program and managed the solicitation in an open and competitive process, resulting in the award of 10 fellowships. This paper discusses the process, the response, results and recommendations for subsequent program years. (authors)

  13. NASA Airborne Astronomy Ambassadors (AAA)

    Science.gov (United States)

    Backman, D. E.; Harman, P. K.; Clark, C.

    2016-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas

  14. Multifunctional Mitochondrial AAA Proteases.

    Science.gov (United States)

    Glynn, Steven E

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

  15. Africa Agribusiness Academy (AAA) Year Report 2014

    NARCIS (Netherlands)

    Nijhoff, G.H.; Vugt, van S.M.

    2015-01-01

    The Africa Agribusiness Academy (AAA) supports African SME agrifood companies in growing their business. An AAA member companies can enhance knowledge, skills and expertise, and get support in accessing finance and markets. By the end of 2014, AAA had 200 members in five countries: Tanzania, Kenya,

  16. Mandibular Angle Fractures: A Clinical and Biomechanical Comparison-the Works of Ellis and Haug.

    Science.gov (United States)

    Haug, Richard H; Serafin, Bethany L

    2008-11-01

    In a series of articles spanning 8 years, Ed Ellis reviewed the clinical results of the treatment of 478 mandibular angle fractures managed by eight different techniques. During a series of benchtop investigations employing polyurethane synthetic mandible replicas, Rich Haug investigated the biomechanical behavior of approximately 15 different techniques designed to reconstruct mandibular angle fractures. This article reviews these two series of investigations in an attempt to gain insight into the biomechanical and biological factors that affect the successful reconstruction of mandibular angle fractures. It appears that the current techniques used to reconstruct mandibular angle fractures are sound from the standpoint of biomechanics within a range of forces encountered during clinical function. It also appears that an unsuccessful reconstruction is based on a biological result of a behavioral issue such as noncompliance, substance abuse, and/or nutritional or immune compromise.

  17. Philip Kurian

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. Philip Kurian. Articles written in Bulletin of Materials Science. Volume 24 Issue 6 December 2001 pp 623-631 Magnetic Materials. Tailoring magnetic and dielectric properties of rubber ferrite composites containing mixed ferrites · M R Anantharaman K A Malini S Sindhu E M ...

  18. Pathophysiology of AAA: heredity vs environment.

    Science.gov (United States)

    Björck, Martin; Wanhainen, Anders

    2013-01-01

    Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Philip Glass : "Koyaanisqatsi" muutub üha aktuaalsemaks / Philip Glass ; interv. Romi Erlach

    Index Scriptorium Estoniae

    Glass, Philip, 1937-

    2003-01-01

    Philip Glass ja tema ansambel esitavad 2. detsembril PÖFFil oma filmimuusika Godfrey Reggio filmile "Koyaanisqatsi" selle linastusel Tallinna linnahallis. Helilooja räägib oma muusikast, ka Arvo Pärdist

  20. Philips LTC 2009/51

    CERN Multimedia

    1999-01-01

    It was part of a range of high-performance monitors (computers screens) that were associated with other units such as Philip's video surveillance systems, cameras or transmission and control equipment. Included in this range of Philips monitors are LTC 2009 (like this one), LTC 2012, LTC 2017 and LTC 2020 Series monochrome monitors. They offer high-performance images with a resolution of 900 TVL (TV-Lines), or in the case of the LTC 2017 monitor, 700 TVL, making them ideal for remote viewing and video applications. The monitor housing consists of a robust rectangular metal case which minimizes interference from external signals and allows “stacking” of monitors when used in large numbers.

  1. Structural Elements Regulating AAA+ Protein Quality Control Machines.

    Science.gov (United States)

    Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

    2017-01-01

    Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

  2. Philip Glass tuleb Eestisse

    Index Scriptorium Estoniae

    2002-01-01

    26. nov. Tallinnas Sakala keskuses toimuvast muusikafestivali NYYD ja Pimedate Ööde filmifestivali ühisprojektist, mis kujutab endast Godfrey Reggio ja Philip Glassi kultusfilmi "Koyaanisqatsi" kontsert-linastust

  3. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    DEFF Research Database (Denmark)

    Kloster, Brian O; Lund, Lars; Lindholt, Jes S

    2016-01-01

    to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. METHODS: The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten...... of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. RESULTS: All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned...... and histology. CONCLUSION: In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human...

  4. Loovkirjutamist õpetab Philip Gross

    Index Scriptorium Estoniae

    2011-01-01

    T.S. Elioti luulepreemia laureaat Philip Gross on Tallinna Ülikooli talvekooli rahvusvahelise kursuse "Poetry: A Conversation between Words and Silence" läbiviija. Oma seminarides keskendub ta lisaks loovkirjutamisele ka loova lugemise vajadusele

  5. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Accumulated adjustments account (AAA). 1.1368-2... adjustments account (AAA). (a) Accumulated adjustments account—(1) In general. The accumulated adjustments account is an account of the S corporation and is not apportioned among shareholders. The AAA is relevant...

  6. Protein quality control in organelles - AAA/FtsH story.

    Science.gov (United States)

    Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

    2013-02-01

    This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The Weekend Effect in AAA Repair.

    Science.gov (United States)

    O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L

    2018-04-18

    Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.

  8. Adesope, AAA

    African Journals Online (AJOL)

    Adesope, AAA. Vol 10, No 1 (2010) - Articles Effect of waste water on vegetable production. Abstract PDF · Vol 10, No 1 (2010) - Articles Willingness to pay for safety label on sugar and vegetable oil among households in South – Western Nigeria Abstract PDF · Vol 10, No 2 (2010) - Articles Analysis of physical and chemical ...

  9. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

    Science.gov (United States)

    Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

    2018-04-09

    The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  10. NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

    Science.gov (United States)

    Backman, D. E.; Clark, C.; Harman, P. K.

    2017-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

  11. The influence of wall stress on AAA growth and biomarkers

    NARCIS (Netherlands)

    Speelman, L.; Hellenthal, F.A.M.V.I.; Pulinx, B.; Bosboom, E.M.H.; Breeuwer, M.; Sambeek, M.R.; Vosse, van de F.N.; Jacobs, M.J.H.M.; Wodzig, W.K.W.H.; Schurink, G.W.H.

    2010-01-01

    Objectives This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or

  12. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    Science.gov (United States)

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

    Science.gov (United States)

    Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

    2018-05-01

    The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Fundamental Characteristics of AAA+ Protein Family Structure and Function.

    Science.gov (United States)

    Miller, Justin M; Enemark, Eric J

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

  15. Assessing heterogeneity in oligomeric AAA+ machines.

    Science.gov (United States)

    Sysoeva, Tatyana A

    2017-03-01

    ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

  16. Differential expression of TRAIL and its receptors relative to calcification in AAA

    International Nuclear Information System (INIS)

    Liu, Xun; Winrow, Vivienne R.; Horrocks, Michael; Stevens, Cliff R.

    2007-01-01

    Abdominal aortic aneurysm (AAA) is commonly associated with atherosclerosis. Human AAA tissue displays cells undergoing all stages of apoptosis. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumour cells but not in normal cells. It has death receptors and decoy receptors. An inhibitor of TRAIL, osteoprotegerin (OPG), is involved in osteogenesis and vascular calcification. We investigated TRAIL and its receptors in AAA compared within normal aorta (NA). Both qualitative and quantitative analyses of calcification in AAA walls were determined using Von Kossa staining and pre-operation computer tomography (CT) scans. There was a significant difference in calcification level at different locations in the AAA wall (p < 0.05). Apoptosis was confirmed in AAA by TUNEL assay. A significant difference in TRAIL and its receptor expression was observed between normal aortae and AAA (p < 0.05). Significant differences were also observed between tissues displaying different extents of calcification for TRAIL mRNA (p < 0.05) by RT-PCR examination and OPG protein (p < 0.01) by protein blotting examination. We propose that this pattern of expression of TRAIL and its receptors may contribute to AAA formation and calcification in the AAA wall

  17. Thinking the "unthinkable": why Philip Morris considered quitting.

    Science.gov (United States)

    Smith, E A; Malone, R E

    2003-06-01

    To investigate the genesis and development of tobacco company Philip Morris's recent image enhancement strategies and analyse their significance. Internal Philip Morris documents, made available by the terms of the Master Settlement Agreement between the tobacco companies and the attorneys general of 46 states, and secondary newspaper sources. Searches of the Philip Morris documents website (www.pmdocs.com) beginning with terms such as "image management" and "identity" and expanding as relevant new terms (consultant names, project names, and dates), were identified, using a "snowball" sampling strategy. In the early 1990s, Philip Morris, faced with increasing pressures generated both externally, from the non-smokers' rights and public health communities, and internally, from the conflicts among its varied operating companies, seriously considered leaving the tobacco business. Discussions of this option, which occurred at the highest levels of management, focused on the changing social climate regarding tobacco and smoking that the tobacco control movement had effected. However, this option was rejected in favour of the image enhancement strategy that culminated with the recent "Altria" name change. This analysis suggests that advocacy efforts have the potential to significantly denormalise tobacco as a corporate enterprise.

  18. Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

    Science.gov (United States)

    Htun, Nay Min; Peter, Karlheinz

    2014-10-01

    Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

    Science.gov (United States)

    Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

    2011-02-11

    FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

  20. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

    Science.gov (United States)

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-03-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

  1. The predictability of Philips

    International Nuclear Information System (INIS)

    Roggen, M.

    2001-01-01

    Philips will be centralizing electric power purchasing for its European branches. The purchasing department needs to have up-to-date and comparable figures on energy consumption within each branch to be able to secure the most profitable contracts. With Energy ICT's real-time multisite on energy registration they are bound to succeed

  2. Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

    Science.gov (United States)

    Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

    2012-01-01

    Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis

    NARCIS (Netherlands)

    Speelman, L.; Bosboom, E.M.H.; Schurink, G.W.H.; Buth, J.; Breeuwer, M.; Jacobs, M.J.; Vosse, van de F.N.

    2009-01-01

    Rupture risk estimation of abdominal aortic aneurysms (AAA) is currently based on the maximum diameter of the AAA. A more critical approach is based on AAA wall stress analysis. For that, in most cases, the AAA geometry is obtained from CT-data and treated as a stress free geometry. However, during

  4. Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines.

    Science.gov (United States)

    Monroe, Nicole; Hill, Christopher P

    2016-05-08

    Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.

    Science.gov (United States)

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research.

  6. Altria means tobacco: Philip Morris's identity crisis.

    Science.gov (United States)

    Smith, Elizabeth A; Malone, Ruth E

    2003-04-01

    Philip Morris Companies, the world's largest and most profitable tobacco seller, has changed its corporate name to The Altria Group. The company has also embarked on a plan to improve its corporate image. Examination of internal company documents reveals that these changes have been planned for over a decade and that the company expects to reap specific and substantial rewards from them. Tobacco control advocates should be alert to the threat Philip Morris's plans pose to industry focused tobacco control campaigns. Company documents also suggest what the vulnerabilities of those plans are and how advocates might best exploit them.

  7. Endovascular abdominal aortic repair for AAA. Anatomical suitability and limitation in Japanese population according to the inclusion criteria of Zenith AAA stent graft

    International Nuclear Information System (INIS)

    Kitagawa, Atsushi; Okita, Yutaka; Okada, Kenji

    2009-01-01

    Since 2007, the EVAR (endovascular abdominal aortic repair) grafts, Zenith, Excluder and Powerlink had been commercially available in Japan. However, a small iliac artery, typical of Japanese population especially in women, was a limiting factor to indicate EVAR. We analyzed the suitability of EVAR in Japanese population according to the inclusion criteria of Zenith AAA stent graft in the current study. From January 2006 to December 2007, 106 AAA (abdominal aortic aneurysm) patients (88 men, 18 women) with a mean age of 73 years were investigated in our institution by multi-slice CT scan in terms of suitability of EVAR, then we measured their abdominal aorta and iliac artery parameters as follows; proximal neck diameter (PND) and length (PNL), common iliac artery diameter (CIAD) and length (CIAL), suprarenal (SNA) and infrarenal neck angulation (INA), external iliac artery diameter (EIAD) and aortic length from the lowest renal artery to the aortic bifurcation (AOL). The inclusion criteria for Zenith AAA stent graft treatment were; PND: 18-28 mm, PNL more than 15 mm, unilateral CIAD less than 20 mm, CIAL at least 10 mm, SNA less than 45 degree and INA less than 60 degree, unilateral EIAD more than 7.5 mm. The indication of EVAR was 25.5% (27/106 patients), and was especially very low in women (5.6%) strictly according to the inclusion criteria of the Zenith AAA stent graft. The main reason of exclusion of EVAR was proximal short neck (40.5%), small iliac artery (30.4%) and infrarenal aortic neck angulation (29.1%). In our analysis, female AAA patients had small PNL and EIAD with angulated neck compared with male AAA ones. Anatomical suitability of EVAR in Japanese population strictly following by the inclusion criteria of Zenith AAA stent graft was low due to their characteristic differences from the European Union (EU) and the United States (US) patients, such as short proximal neck, steep neck angulation and small iliac artery, especially in women. More flexible

  8. The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

    Science.gov (United States)

    Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

    2016-12-01

    The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

  9. APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

    Science.gov (United States)

    Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

    2013-11-01

    To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

  10. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

    Science.gov (United States)

    Kloster, Brian O; Lund, Lars; Lindholt, Jes S

    2016-05-01

    The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

  11. Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

    Science.gov (United States)

    Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

    2012-01-01

    Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for

  12. AAA (2010) CAPD clinical practice guidelines: need for an update.

    Science.gov (United States)

    DeBonis, David A

    2017-09-01

    Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

  13. The LHC at the AAAS

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    The American Association for the Advancement of Science held its annual meeting in the Walter E. Washington Convention Center in Washington D.C. last week.   Veteran science writer Tim Radford introduces LHC scientists during a media briefing at the AAAS annual meeting. Left to right: Felicitas Pauss, Tom LeCompte, Yves Schutz and Nick Hadley. As the world’s largest popular science meeting, the AAAS meeting is a major event in the calendar of science journalists.  At this year’s LHC session, CERN’s coordinator for international relations, Felicitas Pauss, opened the discussion, paving the way for Tom LeCompte of ATLAS, Joe Incandela of CMS, Yves Schutz of ALICE and Monica Pepe-Altarelli of LHCb to report on the status of the first year’s analysis from their experiments.    

  14. Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

    Science.gov (United States)

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

  15. Electron beam characteristics on a Philips SL25

    International Nuclear Information System (INIS)

    Palta, J.R.; Daftari, I.K.; Ayyangar, K.M.; Suntharalingam, N.

    1990-01-01

    Dosimetry measurements at nominal electron energies of 4, 6, 8, 10, 12, 15, 17, 20, and 22 MeV were made for different sized, open-sided applicators on two Philips SL25 linear accelerators. Measurements include beam flatness, percentage depth dose, surface dose, isodose curves, field size dependence, output at extended distances, virtual source position, and required low melting point alloy thickness for field shaping. These measurements are presented to document the characteristics of electron beams with a new type of applicator design on this series of Philips accelerators

  16. The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

    Science.gov (United States)

    König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

    2016-10-06

    Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

    Science.gov (United States)

    Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

    2014-12-15

    For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. CTA Contribution by Evaluation of Treatment AAA

    International Nuclear Information System (INIS)

    Mikulas, J.; Majercik, M.; Klepanec, A.; Balazs, T.; Bazik, R.; Vulev, I.

    2010-01-01

    Over the past decade, the EVAR (Endovascular aortic aneurysm repair) became an accepted treatment of abdominal aortic aneurysms (AAA) as compared with the radical open surgical treatment. Due to the latest generation of stents, 60% of infra renal AAA can be treated by the endovascular method or even percutaneously, without any surgical procedure, and only under the local anesthesia. We retrospectively evaluated the findings of patients following elective EVAR who underwent CTA examination immediately after the procedure and three months after the procedure, for the period from June 2009 to February 2010 (9 months).

  19. The mitochondrial inner membrane AAA metalloprotease family in metazoans.

    Science.gov (United States)

    Juhola, M K; Shah, Z H; Grivell, L A; Jacobs, H T

    2000-09-15

    Three metalloproteases belonging to the AAA superfamily (Yme1p, Afg3p and Rca1p) are involved in protein turnover and respiratory chain complex assembly in the yeast inner mitochondrial membrane. Analysis of the completed genome sequences of Caenorhabditis elegans and Drosophila melanogaster indicates that this gene family typically comprises 3-4 members in metazoans. Phylogenetic analysis reveals three main branches represented, respectively, by Saccharomyces cerevisiae YME1, human SPG7 (paraplegin) and S. cerevisiae AFG3 and RCA1. mt-AAA metalloproteases are weak candidates for several previously studied Drosophila mutants. A full elucidation of the cellular and physiological roles of mt-AAA metalloproteases in metazoans will require the creation of targeted mutations.

  20. Role of AAA(+)-proteins in peroxisome biogenesis and function.

    Science.gov (United States)

    Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

    2016-05-01

    Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

  1. Target dose study of effects of changes in the AAA calculation resolution on lung SABR plan

    International Nuclear Information System (INIS)

    Kim, Dae Il; Son, Sang Jun; Ahn, Bum Seok; Jung, Chi Hoon; Yoo, Suk Hyun

    2014-01-01

    Changing the calculation grid of AAA in Lung SABR plan and to analyze the changes in target dose, and investigated the effects associated with it, and considered a suitable method of application. 4D CT image that was used to plan all been taken with Brilliance Big Bore CT (Philips, Netherlands) and in Lung SABR plan(Eclipse TM ver10.0.42, Varian, the USA), use anisotropic analytic algorithm(AAA, ver.10, Varian Medical Systems, Palo Alto, CA, USA) and, was calculated by the calculation grid 1.0, 3.0, 5.0 mm in each Lung SABR plan. Lung SABR plan of 10 cases are using each of 1.0 mm, 3.0 mm, 5.0 mm calculation grid, and in case of use a 1.0 mm calculation grid V98 of the prescribed dose is about 99.5%±1.5%, Dmin of the prescribed dose is about 92.5±1.5% and Homogeneity Index(HI) is 1.0489±0.0025. In the case of use a 3.0 mm calculation grid V98 dose of the prescribed dose is about 90±4.5% , Dmin of the prescribed dose is about 87.5±3% and HI is about 1.07±1. In the case of use a 5.0 mm calculation grid V98 dose of the prescribed dose is about 63±15%, Dmin of the prescribed dose is about 83±4% and HI is about 1.13±0.2, respectively. The calculation grid of 1.0 mm is better improves the accuracy of dose calculation than using 3.0 mm and 5.mm, although calculation times increase in the case of smaller PTV relatively. As lung, spread relatively large and low density and small PTV, it is considered and good to use a calculation grid of 1.0 mm

  2. A methodology for developing anisotropic AAA phantoms via additive manufacturing.

    Science.gov (United States)

    Ruiz de Galarreta, Sergio; Antón, Raúl; Cazón, Aitor; Finol, Ender A

    2017-05-24

    An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of biomechanical factors for rupture risk assessment. AAA phantoms could be used for experimental validation of the numerical studies and for pre-intervention testing of endovascular grafts. We have applied multi-material 3D printing technology to manufacture idealized AAA phantoms with anisotropic mechanical behavior. Different composites were fabricated and the phantom specimens were characterized by biaxial tensile tests while using a constitutive model to fit the experimental data. One composite was chosen to manufacture the phantom based on having the same mechanical properties as those reported in the literature for human AAA tissue; the strain energy and anisotropic index were compared to make this choice. The materials for the matrix and fibers of the selected composite are, respectively, the digital materials FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the composite is equal to 0.15. The differences between the composite behavior and the AAA tissue are small, with a small difference in the strain energy (0.4%) and a maximum difference of 12.4% in the peak Green strain ratio. This work represents a step forward in the application of 3D printing technology for the manufacturing of AAA phantoms with anisotropic mechanical behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

    Science.gov (United States)

    Wang, Dile; Qu, Bihui; He, Tao

    2017-08-01

    The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease AAA size decreased in the control group (PAAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P7.8 mmol/L (14/24), AAA size (P7.8 mmol/L (11/24), AAA size (PAAA therapy.

  4. Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

    Science.gov (United States)

    Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

    2016-02-01

    Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

  5. "The Big WHY": Philip Morris's failed search for corporate social value.

    Science.gov (United States)

    McDaniel, Patricia A; Malone, Ruth E

    2012-10-01

    We examined Philip Morris USA's exploration of corporate social responsibility practices and principles and its outcome. We analyzed archival internal tobacco industry documents, generated in 2000 to 2002, related to discussions of corporate social responsibility among a Corporate Responsibility Taskforce and senior management at Philip Morris. In exploring corporate social responsibility, Philip Morris executives sought to identify the company's social value-its positive contribution to society. Struggling to find an answer, they considered dramatically changing the way the company marketed its products, apologizing for past actions, and committing the company to providing benefits for future generations. These ideas were eventually abandoned. Despite an initial call to distinguish between social and economic value, Philip Morris ultimately equated social value with providing shareholder returns. When even tobacco executives struggle to define their company's social value, it signals an opening to advocate for endgame scenarios that would encourage supply-side changes appropriate to the scale of the tobacco disease epidemic and consistent with authentic social value.

  6. Aortocaval fistula (ACF) in patients operated for ruptured aortic aneurysm (rAAA)

    DEFF Research Database (Denmark)

    Warning, Karina; Houlind, Kim Christian; Ravn, Hans

    Aortocaval fistula (ACF) in patients operated for Ruptured Acute Aorta Aneurysm (rAAA): A surgical challenge. Introduction Aortocaval fistula is a rare complication of abdominal aortic aneurysm (AAA). It been reported to be present in less than 1% of all AAAs. ACF arise in patients with large...... aneurysms and is typically discovered peroperatively in patients with rAAA. Open surgical treatment is associated with high mortality and morbidity. ACF is a result of spontaneously rupture of large atherosclerotic aneurysms into the inferior vena cava in 80%, 15% arise after trauma and 5% are iatrogenic....... Patients During the last 9 month, we have operated three cases with rAAA and ACF. All patients had an open, acute operation. All ACFs detected during operation. Common for all operations was that the patients had large aneurysms (>10 cm) and extensive bleeding (3-4 l) immediately when the aneurysm...

  7. Altria Means Tobacco: Philip Morris’s Identity Crisis

    Science.gov (United States)

    Smith, Elizabeth A.; Malone, Ruth E.

    2003-01-01

    Philip Morris Companies, the world’s largest and most profitable tobacco seller, has changed its corporate name to The Altria Group. The company has also embarked on a plan to improve its corporate image. Examination of internal company documents reveals that these changes have been planned for over a decade and that the company expects to reap specific and substantial rewards from them. Tobacco control advocates should be alert to the threat Philip Morris’s plans pose to industryfocused tobacco control campaigns. Company documents also suggest what the vulnerabilities of those plans are and how advocates might best exploit them. PMID:12660196

  8. Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

    Science.gov (United States)

    Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

    2017-07-01

    The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is

  9. Exhibition at the AAA library

    DEFF Research Database (Denmark)

    2013-01-01

    Sonnesgade 11 The exhibition at the AAA library presents selected work produced by students prior to the exhibition of installations in project and praxis constructing an archive at Sonnesgade 11. The exhibition at Sonnesgade 11 was the culmination of collaboration with SLETH architects and studio...

  10. On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics.

    Science.gov (United States)

    Riveros, Fabián; Martufi, Giampaolo; Gasser, T Christian; Rodriguez-Matas, Jose F

    2015-09-01

    Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

  11. Functional characterization of the mammalian iAAA protease subunit, YME1L

    OpenAIRE

    Majczak, Joanna

    2008-01-01

    The iAAA protease is an ATP-dependent proteolytic complex in the mitochondrial inner membrane and belongs to the highly conserved family of AAA proteins. In the yeast Saccharomyces cerevisiae, the iAAA protease is a homo-oligomeric complex composed of Yme1p subunits which are active in the intermembrane space and mediate protein quality control. Yeast cells lacking Yme1p are characterized by pleiotropic phenotypes including a respiratory deficiency at elevated temperature and an aberrant mito...

  12. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

    Science.gov (United States)

    Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

    2017-05-04

    Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

  13. Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

    Science.gov (United States)

    Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

    2011-07-01

    ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

  14. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

    OpenAIRE

    Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, K?r?ad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor pro...

  15. Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

    Science.gov (United States)

    Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

    2016-09-01

    Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

  16. "Clockwork": Philip Pullman's Posthuman Fairy Tale

    Science.gov (United States)

    Gooding, Richard

    2011-01-01

    This article examines the connections between posthumanism and narrative form in Philip Pullman's "Clockwork." Beginning with an account of Pullman's materialism, it argues that the novel represents consciousness and agency as emergent properties of matter, a position that manifests itself first in the tale's figurative language and later in the…

  17. Identifying patients with AAA with the highest risk following endovascular repair.

    Science.gov (United States)

    Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

    2012-08-01

    It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

  18. Public versus internal conceptions of addiction: An analysis of internal Philip Morris documents.

    Directory of Open Access Journals (Sweden)

    Jesse Elias

    2018-05-01

    Full Text Available Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement.We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris's move from public denial to public affirmation of nicotine's addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA, the United States government's filing of the Racketeer Influenced and Corrupt Organizations (RICO suit, and the Institute of Medicine's (IoM's endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs. While Philip Morris's public statements reinforce the idea that nicotine's pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis.Philip Morris's research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine's pharmacology, the industry's continued aggressive advertising

  19. Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

    Science.gov (United States)

    Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

    2016-05-01

    The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months. Selective intra-procedural AAA sac embolization in patients with p-MRF is safe and could be an effective method to reduce ELIIp. Further studies are mandatory to support these results at long-term follow up. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  20. PENGARUH KEPUASAN KONSUMEN TERHADAP KEPUTUSAN PEMBELIAN LAMPU PHILIPS (STUDI KASUS PADA MAHASISWA TELKOM UNIVERSITY

    Directory of Open Access Journals (Sweden)

    Rahmat Hidayat

    2016-03-01

      Abstrak - Berubahnya pasar menjadi 3.0. ini memacu para produsen untuk tetap melakukan inovasi, agar tetap konsisten ditengah persaingan pasar yang semakin ketat. Produsen Lampu Philips, juga mengalami pergeseran menuju persaingan pasar yang semakin ketat Jenis penelitian ini ialah Deskriptif bersifat kausal, dengan tujuan untuk melihat pengaruh kepuasan konsumen terhadap keputusan pembelian lampu Philips . Subjek penelitian adalah pada mahasiswa Telkom University. Jumlah responden sebesar 100 orang mahasiswa Telkom University. Analisa menggunakan Regresi Sederhana. Hasil penelitian menunjukkan adanya pengaruh kepuasan konsumen terhadap keputusan pembelian lampu Philips pada mahasiswa Telkom University dengan nilai p = .000, koefisien korelasi sebesar 0.791 (R=0.791, dan koefisien determinan (R Square / R2 sebesar 62,6%.   Kata Kunci : Keputusan Pembelian , Kepuasan Konsumen, Lampu Philips

  1. Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

    Science.gov (United States)

    Abbas, A; Smith, A; Cecelja, M; Waltham, M

    2012-02-01

    AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  2. Stress Testing of the Philips 60W Replacement Lamp L Prize Entry

    Energy Technology Data Exchange (ETDEWEB)

    Poplawski, Michael E.; Ledbetter, Marc R.; Smith, Mark

    2012-04-24

    The Pacific Northwest National Laboratory, operated by Battelle for the U.S. Department of Energy, worked with Intertek to develop a procedure for stress testing medium screw-base light sources. This procedure, composed of alternating stress cycles and performance evaluation, was used to qualitatively compare and contrast the durability and reliability of the Philips 60W replacement lamp L Prize entry with market-proven compact fluorescent lamps (CFLs) with comparable light output and functionality. The stress cycles applied simultaneous combinations of electrical, thermal, vibration, and humidity stresses of increasing magnitude. Performance evaluations measured relative illuminance, x chromaticity and y chromaticity shifts after each stress cycle. The Philips L Prize entry lamps appear to be appreciably more durable than the incumbent energy-efficient technology, as represented by the evaluated CFLs, and with respect to the applied stresses. Through the course of testing, all 15 CFL samples permanently ceased to function as a result of the applied stresses, while only 1 Philips L Prize entry lamp exhibited a failure, the nature of which was minor, non-destructive, and a consequence of a known (and resolved) subcontractor issue. Given that current CFL technology appears to be moderately mature and no Philips L Prize entry failures could be produced within the stress envelope causing 100 percent failure of the benchmark CFLs, it seems that, in this particular implementation, light-emitting diode (LED) technology would be much more durable in the field than current CFL technology. However, the Philips L Prize entry lamps used for testing were carefully designed and built for the competition, while the benchmark CFLs were mass produced for retail sale—a distinction that should be taken into consideration. Further reliability testing on final production samples would be necessary to judge the extent to which the results of this analysis apply to production versions

  3. From adversary to target market: the ACT-UP boycott of Philip Morris.

    Science.gov (United States)

    Offen, N; Smith, E A; Malone, R E

    2003-06-01

    In 1990, the AIDS Coalition to Unleash Power (ACT-UP) sparked a year long boycott of Philip Morris's Marlboro cigarettes and Miller beer. The boycott protested the company's support of Senator Jesse Helms (R-North Carolina), a leading opponent of AIDS funding and civil rights for lesbian, gay, bisexual and transgender (LGBT) people. ACT-UP demanded that Philip Morris sever its ties with Helms and acknowledge its responsibility to the LGBT community and to people with AIDS. To assess the impact of the boycott on the LGBT community, the tobacco industry, and the tobacco control movement; and to determine what lessons tobacco control advocates can extract from this case. Internal tobacco industry documents and newspaper archives. Search of tobacco industry documents websites using "boycott", "ACT-UP", "gay", and other terms. Philip Morris used the boycott to its own advantage. It exploited differences within the community and settled the boycott by pledging large donations to combat AIDS. Through corporate philanthropy, Philip Morris gained entrée to the LGBT market without appearing gay friendly. Many LGBT organisations, thirsty for recognition and funding from mainstream corporations, welcomed Philip Morris's overtures without considering the health hazards of tobacco. Unless the goal of a boycott is to convince the tobacco industry to abandon tobacco altogether, such actions invite the industry to expand its marketing under the guise of philanthropy. Tobacco control advocates should be clear about goals and acceptable settlement terms before participating in a boycott of a tobacco company.

  4. Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

    Science.gov (United States)

    Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

    2018-02-01

    Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40% are risk factors for ELIIp. No PMF was able to predict the ELIIp evolution. The relative high rate of re-interventions, could suggest the need of adjunctive/preventing primary procedures in patients at high-risk for ELIIp.

  5. Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

    Science.gov (United States)

    Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

    2017-01-01

    There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights

  6. Parallel Agent-as-a-Service (P-AaaS Based Geospatial Service in the Cloud

    Directory of Open Access Journals (Sweden)

    Xicheng Tan

    2017-04-01

    Full Text Available To optimize the efficiency of the geospatial service in the flood response decision making system, a Parallel Agent-as-a-Service (P-AaaS method is proposed and implemented in the cloud. The prototype system and comparisons demonstrate the advantages of our approach over existing methods. The P-AaaS method includes both parallel architecture and a mechanism for adjusting the computational resources—the parallel geocomputing mechanism of the P-AaaS method used to execute a geospatial service and the execution algorithm of the P-AaaS based geospatial service chain, respectively. The P-AaaS based method has the following merits: (1 it inherits the advantages of the AaaS-based method (i.e., avoiding transfer of large volumes of remote sensing data or raster terrain data, agent migration, and intelligent conversion into services to improve domain expert collaboration; (2 it optimizes the low performance and the concurrent geoprocessing capability of the AaaS-based method, which is critical for special applications (e.g., highly concurrent applications and emergency response applications; and (3 it adjusts the computing resources dynamically according to the number and the performance requirements of concurrent requests, which allows the geospatial service chain to support a large number of concurrent requests by scaling up the cloud-based clusters in use and optimizes computing resources and costs by reducing the number of virtual machines (VMs when the number of requests decreases.

  7. Philip Glass muusika kirjutamisest filmile ja teistele kunstiliikidele : "Koyaanisqatsi" lugu / Philip Glass ; interv. Charles Merrell Berg, tõlk. Kaia Sisask

    Index Scriptorium Estoniae

    Glass, Philip, 1937-

    2004-01-01

    Philip Glass ja tema ansambel esitasid 2. detsembril 2003 PÖFFil oma filmimuusika Godfrey Reggio filmile "Koyaanisqatsi" selle linastusel Tallinna linnahallis. Intervjuu on tõlgitud seda sündmust silmas pidades. Järgneb apr. 2004, lk. 74-82

  8. AAA+ Machines of Protein Destruction in Mycobacteria.

    Science.gov (United States)

    Alhuwaider, Adnan Ali H; Dougan, David A

    2017-01-01

    The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli , we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.

  9. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

    Science.gov (United States)

    Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics. PMID:28748186

  10. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.

    Science.gov (United States)

    Elsholz, Alexander K W; Birk, Marlene S; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis . We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics.

  11. Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

    Science.gov (United States)

    An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

    2015-10-01

    Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

  12. The AAA protein spastin possesses two levels of basal ATPase activity.

    Science.gov (United States)

    Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

    2018-04-30

    The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

  13. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

    Science.gov (United States)

    Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

    2017-03-17

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

  14. Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

    Science.gov (United States)

    Guebert, Alexandra; Conroy, Leigh; Weppler, Sarah; Alghamdi, Majed; Conway, Jessica; Harper, Lindsay; Phan, Tien; Olivotto, Ivo A; Smith, Wendy L; Quirk, Sarah

    2018-04-25

    Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMC CTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breast CTV V 95% , was AAA for breast radiotherapy is not expected to result in changes in clinical practice for prescribing or planning breast radiotherapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  15. Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

    International Nuclear Information System (INIS)

    Arakaki, Tracy; Le Trong, Isolde; Phizicky, Eric; Quartley, Erin; DeTitta, George; Luft, Joseph; Lauricella, Angela; Anderson, Lori; Kalyuzhniy, Oleksandr; Worthey, Elizabeth; Myler, Peter J.; Kim, David; Baker, David; Hol, Wim G. J.; Merritt, Ethan A.

    2006-01-01

    The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD) using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R free = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif

  16. Validation of Varian's AAA algorithm with focus on lung treatments

    International Nuclear Information System (INIS)

    Roende, Heidi S.; Hoffmann, Lone

    2009-01-01

    The objective of this study was to examine the accuracy of the Anisotropic Analytical Algorithm (AAA). A variety of different field configurations in homogeneous and in inhomogeneous media (lung geometry) was tested for the AAA algorithm. It was also tested against the present Pencil Beam Convolution (PBC) algorithm. Materials and methods. Two dimensional (2D) dose distributions were measured for a variety of different field configurations in solid water with a 2D array of ion chambers. The dose distributions of patient specific treatment plans in selected transversal slices were measured in a Thorax lung phantom with Gafchromic dosimetry films. A Farmer ion chamber was used to check point doses in the Thorax phantom. The 2D dose distributions were evaluated with a gamma criterion of 3% in dose and 3 mm distance to agreement (DTA) for the 2D array measurements and for the film measurements. Results. For AAA, all fields tested in homogeneous media fulfilled the criterion, except asymmetric fields with wedges and intensity modulated plans where deviations of 5 and 4%, respectively, were seen. Overall, the measured and calculated 2D dose distributions for AAA in the Thorax phantom showed good agreement - both for 6 and 15 MV photons. More than 80% of the points in the high dose regions met the gamma criterion, though it failed at low doses and at gradients. For the PBC algorithm only 30-70% of the points met the gamma criterion. Conclusion. The AAA algorithm has been shown to be superior to the PBC algorithm in heterogeneous media, especially for 15 MV. For most treatment plans the deviations in the lung and the mediastinum regions are below 3%. However, the algorithm may underestimate the dose to the spinal cord by up to 7%

  17. “The Big WHY”: Philip Morris’s Failed Search for Corporate Social Value

    Science.gov (United States)

    Malone, Ruth E.

    2012-01-01

    Objectives. We examined Philip Morris USA’s exploration of corporate social responsibility practices and principles and its outcome. Methods. We analyzed archival internal tobacco industry documents, generated in 2000 to 2002, related to discussions of corporate social responsibility among a Corporate Responsibility Taskforce and senior management at Philip Morris. Results. In exploring corporate social responsibility, Philip Morris executives sought to identify the company’s social value—its positive contribution to society. Struggling to find an answer, they considered dramatically changing the way the company marketed its products, apologizing for past actions, and committing the company to providing benefits for future generations. These ideas were eventually abandoned. Despite an initial call to distinguish between social and economic value, Philip Morris ultimately equated social value with providing shareholder returns. Conclusions. When even tobacco executives struggle to define their company’s social value, it signals an opening to advocate for endgame scenarios that would encourage supply-side changes appropriate to the scale of the tobacco disease epidemic and consistent with authentic social value. PMID:22897536

  18. Usability laboratories at Philips : supporting research, development, and design for consumer and professional products

    NARCIS (Netherlands)

    Vries, de G.; Gelderen, van T.; Brigham, F.

    1994-01-01

    This paper describes two of the usability laboratories at Philips, discusses practical issues arising from our experience using the facilities, gives an example of a typical usability evaluation, and briefly outlines our vision for the future of the laboratories. Usability tests at Philips can

  19. Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

    Science.gov (United States)

    Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

    2017-09-18

    Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. A. Philip Randolph: Integration in the Workplace.

    Science.gov (United States)

    Wright, Sarah

    This biography for younger readers describes the life of A. Philip Randolph, the civil rights activist who organized the labor union for Pullman car porters, the Brotherhood of Sleeping Car Porters. The book presents an overview of the civil rights movement in the United States while documenting the part Randolph played as advocate for African…

  1. Campaign to counter a deteriorating consumer market: Philip Morris's Project Sunrise.

    Science.gov (United States)

    Givel, M

    2013-02-01

    From 1997 to 2000, Philip Morris implemented Project Sunrise. This paper discusses the impact of this project on national and Philip Morris's cigarette unit sales, public opinion about smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use. A qualitative archival content analysis of Project Sunrise from 1997 to 2000, and a descriptive statistical analysis of cigarette unit sales and operating profits, acceptability of smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use from 1996 to 2006. Qualitative data sources related to Project Sunrise found on WebCat, Pubmed.com, LexisNexis Academic and Philip Morris's website, and archived tobacco industry documents were analysed using NVivo Version 9.0. A descriptive statistical analysis of cigarette unit sales, public opinion about smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use was undertaken. Project Sunrise was a high-level strategic corporate plan to maintain profits that included four possible scenarios resulting in seven interwoven strategies. However, national prevalence rates for tobacco use declined, sales of national and Philip Morris cigarettes declined, operating profits remained at substantially lower levels after 2000 from 2001 to 2006, and a large majority of Americans agreed that there were significant health dangers associated with smoking and secondhand tobacco smoke. The impact of Project Sunrise, including countering the anti-tobacco movement, was less than successful in the USA. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  2. The Airborne Astronomy Ambassadors (AAA) Program and NASA Astrophysics Connections

    Science.gov (United States)

    Backman, Dana Edward; Clark, Coral; Harman, Pamela

    2018-01-01

    The NASA Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content delivery, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong’s B703 science research aircraft facility in Palmdale, California, including interactions with NASA astrophysics & planetary science Subject Matter Experts (SMEs) during science flights on SOFIA, and (3) continuing post-flight opportunities for teacher & student connections with SMEs.

  3. Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

    Science.gov (United States)

    Sypert, David; Van Dyke, Kenneth; Dhillon, Namrata; Elliott, John O; Jordan, Kim

    The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

  4. From adversary to target market: the ACT-UP boycott of Philip Morris

    OpenAIRE

    Offen, N; Smith, E; Malone, R

    2003-01-01

    BACKGROUND: In 1990, the AIDS Coalition to Unleash Power (ACT-UP) sparked a year long boycott of Philip Morris's Marlboro cigarettes and Miller beer. The boycott protested the company's support of Senator Jesse Helms (R-North Carolina), a leading opponent of AIDS funding and civil rights for lesbian, gay, bisexual and transgender (LGBT) people. ACT-UP demanded that Philip Morris sever its ties with Helms and acknowledge its responsibility to the LGBT community and to people with AIDS. OBJECTI...

  5. Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

    Science.gov (United States)

    Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

    2014-01-01

    In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

  6. Tensions within an industrial research laboratory: the Philips laboratory's x-ray department between the wars

    NARCIS (Netherlands)

    Boersma, F.K.

    2003-01-01

    Tensions arose in the X-ray department of the Philips research laboratory during the interwar period, caused by the interplay among technological development, organizational culture, and individual behavior. This article traces the efforts of Philips researchers to find a balance between their

  7. Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

    Science.gov (United States)

    Khashram, M; Jones, G T; Roake, J A

    2015-08-01

    There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  8. Barn music at St Donat's castle / Philip Gross

    Index Scriptorium Estoniae

    Gross, Philip, 1952-

    2011-01-01

    Muusikafestivalist "Vale of Glamorgan", mis oli 2010. a. pühendatud Arvo Pärdile. Eesti kammermuusikaansambli Resonabilis kavas oli ka festivali tellimusel valminud uelsi helilooja Gareth Peredur Churchilli "Vocable", mille teksti kirjutas Philip Gross. Festivalikontsertide muljeid leiab Grossi luuletsüklis "Barn music" (avaldatud samas ajakirjanumbris, lk. 42-43)

  9. Peak AAA Fatty Acid Homolog Contaminants Present in the Dietary Supplement l-Tryptophan Associated with the Onset of Eosinophilia-Myalgia Syndrome.

    Science.gov (United States)

    Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-05-22

    The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1 - 7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018. Published by Elsevier B.V.

  10. Multibands tunneling in AAA-stacked trilayer graphene

    Science.gov (United States)

    Redouani, Ilham; Jellal, Ahmed; Bahaoui, Abdelhadi; Bahlouli, Hocine

    2018-04-01

    We study the electronic transport through np and npn junctions for AAA-stacked trilayer graphene. Two kinds of gates are considered where the first is a single gate and the second is a double gate. After obtaining the solutions for the energy spectrum, we use the transfer matrix method to determine the three transmission probabilities for each individual cone τ = 0 , ± 1 . We show that the quasiparticles in AAA-stacked trilayer graphene are not only chiral but also labeled by an additional cone index τ. The obtained bands are composed of three Dirac cones that depend on the chirality indexes. We show that there is perfect transmission for normal or near normal incidence, which is a manifestation of the Klein tunneling effect. We analyze also the corresponding total conductance, which is defined as the sum of the conductance channels in each individual cone. Our results are numerically discussed and compared with those obtained for ABA- and ABC-stacked trilayer graphene.

  11. SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

    Science.gov (United States)

    Yuan, Y; Duan, J; Popple, R; Brezovich, I

    2012-06-01

    To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

  12. PHILIP GlASS: SCREEN MUSIC

    Directory of Open Access Journals (Sweden)

    Neretina Maina S.

    2012-12-01

    Full Text Available Research is devoted to the music of contemporary composer Philip Glass, which he wrote specifically for the movies including feature and documentary films by American, British and Australian directors (M.Scorsese, E.Morris, S.Daldry, P.Weir etc.. It makes a connection of the composition technologies between his filmmusic and his artmusic written in the aesthetics of minimalism (the repetition and additive processes. The works in collaboration with director G.Reggio highlights as top Glass’ creative at the film industry. It also covers the principles of compilation the composer’s music for a variety of screen opuses, movies and commercials.

  13. Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis

    NARCIS (Netherlands)

    Speelman, L.; Bosboom, E.M.H.; Schurink, G.W.H.; Buth, J.; Breeuwer, M.; Jacobs, M.J.H.M.; Van De Vosse, F.N.

    2009-01-01

    An abdominal aortic aneurysm (AAA) is a local dilation in the abdominal aorta of more than 50% of the original diameter and occurs in about 1 of 20 men over 65 years of age [1]. The largest threat for an AAA is rupture. Aortic repair is considered when the risk of rupture exceeds the risk of the

  14. Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.

    Science.gov (United States)

    Lin, Chien-Chu; Su, Shih-Chieh; Su, Ming-Yuan; Liang, Pi-Hui; Feng, Chia-Cheng; Wu, Shih-Hsiung; Chang, Chung-I

    2016-05-03

    The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A pull-back algorithm to determine the unloaded vascular geometry in anisotropic hyperelastic AAA passive mechanics.

    Science.gov (United States)

    Riveros, Fabián; Chandra, Santanu; Finol, Ender A; Gasser, T Christian; Rodriguez, Jose F

    2013-04-01

    Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

  16. Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

    Science.gov (United States)

    Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

    2016-08-01

    The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

  17. Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.

    Science.gov (United States)

    Bhat, Javaid Y; Thieulin-Pardo, Gabriel; Hartl, F Ulrich; Hayer-Hartl, Manajit

    2017-01-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.

  18. Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

    Science.gov (United States)

    O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

    2015-02-01

    Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Increased levels of thioredoxin in patients with abdominal aortic aneurysms (AAAs). A potential link of oxidative stress with AAA evolution

    DEFF Research Database (Denmark)

    Martinez-Pinna, R; Lindholt, Jes S.; Blanco-Colio, L M

    2010-01-01

    Oxidative stress is a main mechanism involved in vascular pathologies. Increased thioredoxin (TRX) levels have been observed in several oxidative stress-associated cardiovascular diseases. We aim to test the potential role of TRX as a biomarker of oxidative stress in abdominal aortic aneurysm (AAA)....

  20. André-Philip Lemke näitus Tallinnas / Mari Laaniste

    Index Scriptorium Estoniae

    Laaniste, Mari, 1977-

    1998-01-01

    Saksa kunstniku André-Philip Lemke (1970) näitus "Üks-üks armsa Jumala kasuks" 17. augustist Saksa Kultuuriinstituudis. Tööd on valgele paberile tavalise sinise pastapliiatsiga kirjutatud-joonistatud

  1. Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

    Science.gov (United States)

    Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

    2018-01-15

    Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decrease elastase-induced AAA development

    DEFF Research Database (Denmark)

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel

    2017-01-01

    Abdominal aortic aneurysm (AAA) evolution is unpredictable. Moreover, no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA have not been addressed. Galectin-3 levels were increased in plasma...... of AAA patients (n=225) compared to controls (n=100). Moreover, galectin-3 concentrations were associated with need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared to healthy aortas. Experimental AAA...... in mice was induced by aortic elastase perfusion. Mice were treated i.v. with the galectin-3 inhibitor modified citrus pectin (MCP, 10mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared to control mice...

  3. AAA application in diagnosis exams in a large public hospital, RS, Brazil; Aplicacao do AAA na realizacao de exames diagnosticos em um hospital publico de grande porte

    Energy Technology Data Exchange (ETDEWEB)

    Bacelar, A.; Ferret, A.A.; Vanni, S.; Galhardi, M.P.; Lykawka, R., E-mail: abacelar@hepa.ufrgs.br, E-mail: allferret@gmail.com, E-mail: svanni@hepa.ufrgs.br, E-mail: mpgalhardi@gmail.com, E-mail: rlykawka@hepa.ufrgs.br [Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS (Brazil)

    2013-10-01

    Objective: the initiative AAA - Awareness , Appropriateness and Audit , promotes consciousness ( Awareness) , fitness ( Appropriateness ) and Audit ( Audit) . This paper analyzes the application of the concept in the AAA requests and justifications examinations using ionizing radiation within a large public hospital. Materials and methods: we collected and analyzed data between the years 2011 and 2012, concerning the number of exams performed with the use of radiation and their justifications. After, we sought to raise awareness of the clinical team through training on the risks and benefits of the various modalities of the radiology department and the need to justify the use of ionizing radiation on health. After the data were collected again of test requests for verification of the effectiveness of training. Results: the mean requests that need to be appropriate to the AAA in the last quarter of 2011 was 75 % lower than the average demands of the first quarter, matched against the last two months of 2012 increased by up to four times the number requests that require improvements in relation to the excellent results obtained in July 2012. Conclusion: it is shown in this paper the need of implementing this initiative AAA continuously added to the clinical staff awareness about the risk of the use of ionizing radiation, the appropriateness of the requests of these tests , as well as the control of this process in order to optimize use of ionizing radiation on health.

  4. SOFIA Technology: The NASA Airborne Astronomy Ambassador (AAA) Experience and Online Resources

    Science.gov (United States)

    Clark, C.; Harman, P. K.; Backman, D. E.

    2016-12-01

    SOFIA, an 80/20 partnership of NASA and the German Aerospace Center (DLR), consists of a modified Boeing 747SP carrying a reflecting telescope with an effective diameter of 2.5 meters. SOFIA is the largest airborne observatory in the world, capable of observations impossible for even the largest and highest ground-based telescopes. The SOFIA Program Office is at NASA ARC, Moffett Field, CA; the aircraft is based in Palmdale, CA. During its planned 20-year lifetime, SOFIA will foster development of new scientific instrumentation and inspire the education of young scientists and engineers. Astrophysicists are awarded time on SOFIA to study many kinds of astronomical objects and phenomena. Among the most interesting are: Star birth, evolution, and death Formation of new planetary systems Chemistry of complex molecules in space Planet and exoplanet atmospheres Galactic gas & dust "ecosystems" Environments around supermassive black holes SOFIA currently has eight instruments, five US-made and three German. The instruments — cameras, spectrometers, and a photometer,— operate at near-, mid- and far-infrared wavelengths, each spectral range being best suited to studying particular celestial phenomena. NASA's Airborne Astronomy Ambassadors' (AAAs) experience includes a STEM immersion component. AAAs are onboard during two overnight SOFIA flights that provide insight into the acquisition of scientific data as well as the interfaces between the telescope, instrument, & aircraft. AAAs monitor system performance and view observation targets from their dedicated workstation during flights. Future opportunities for school district partnerships leading to selection of future AAA cohorts will be offered in 2018-19. AAAs may access public archive data via the SOFIA Data Cycle System (DCS) https://dcs.sofia.usra.edu/. Additional SOFIA science and other resources are available at: www.sofia.usra.edu, including lessons that use photovoltaic circuits, and other technology for the

  5. Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

    Science.gov (United States)

    Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

    2017-07-24

    This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (pAAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

  6. Intraoperative platelet and plasma improves survival in patients operated for a rAAA: a follow-up evaluation

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Swiatek, F.; Jorgensen, L.

    2008-01-01

    OBJECTIVES: Continued haemorrhage remains a significant contributor to mortality in massively transfused patients. We found that early administration of platelets and plasma reduced mortality from 54% to 36% in rAAA patients. The aim of the present evaluation was to evaluate whether reduced...... mortality in rAAA patients related to a pro-active transfusion therapy is maintained. DESIGN: Single-centre observational study. METHODS: Mortality of patients operated for rAAA 2006-07 was compared to that of patients operated 2004-05 (intervention group; n=50) and 2002-04 (control group, n=82). RESULTS......: 64 consecutive patients with rAAA received, similar to the intervention group, more platelets (5 and 4 vs. 0 units, P

  7. Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

    Science.gov (United States)

    Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

    2012-07-06

    Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

  8. Philip Morris changes its name, but not its harmful practices.

    Science.gov (United States)

    Myers, M L

    2002-09-01

    After spending more than $250 million on an advertising campaign to improve its name and reputation, Philip Morris has abruptly shifted course and decided instead to change its corporate name-to The Altria Group, Inc.

  9. Evaluating the calculation accuracy of AAA algorithm for the situation with small fields in bone by monte carlo

    International Nuclear Information System (INIS)

    Zhang Yanqiu; Qiu Xiaoping; Yang Zhen; Lu Zhiping

    2011-01-01

    In order to evaluate the calculation accuracy of Anisotropic Analytical Algorithm (AAA) for the situation with small fields in a water-bone phantom using Monte Carlo simulation as benchmarks. A water phantom with a bone slab was built,in which the depth dose (DD) and off-axis ratio (OAR) for field 2 cm x 2 cm to field 8 cm x 8 cm were calculated by AAA algorithms, PBC algorithms (as comparison), and Monte Carlo (MC) simulation. The evaluation of algorithms by MC simulation was achieved by the comparisons of DD and the 1 dimension gamma analysis of OAR. It was shown that both of AAA algorithm and PBC algorithm overestimated the DD in bone region, and the dose differences ranged from 2.16%-2.7%, 1.4%-2.03%, respectively. AAA algorithm and PBC algorithm underestimated the DD in back of bone region, and the dose differences ranged from -0.39% - -1.19%, -0.13% - -0.4%, respectively. AAA algorithm and PBC algorithm overestimated the dose of field inner edge and field outer edge,respectively. One dimension gamma analysis indicated that AAA algorithm and PBC algorithm gamma pass rate was 100%, 100%, 100%, 86%, 100%, 100%, 72%, 64%, respectively. In bone medium,the dose calculated by AAA was slightly higher than MC simulation, the calculation accuracy was not evidently higher than PBC. (authors)

  10. Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

    Science.gov (United States)

    Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

    2017-12-08

    Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, D [Kanagawa Cancer Center, Yokohama, Kanagawa (Japan); Takahashi, R [Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto, Tokyo (Japan); Kamima, T [Cancer Institute Hospital Japanese Foundation for Cancer Research, Koto, Tokyo (Japan); Baba, H [The National Cancer Center Hospital East, Kshiwa, Chiba (Japan); Yamamoto, T; Kubo, Y [Otemae Hospital, Chuo-ku, Osaka (Japan); Ishibashi, S; Higuchi, Y [Sasebo City General Hospital, Sasebo, Nagasaki (Japan); Tani, K [St Luke’s International Hospital, Tokyo, Tokyo (Japan); Tachibana, H [National Cancer Center, Kashiwa, Chiba (Japan)

    2016-06-15

    Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU, Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)

  12. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

    Science.gov (United States)

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

    2017-11-15

    Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  13. Philip Atsu Afeadie (2016). Workplace Anguish and Pleasure in ...

    African Journals Online (AJOL)

    Philip Atsu Afeadie's book, Workplace Anguish and Pleasure in Northern Nigeria: Exactions of Colonial ... the author reveals in six chapters the oft-neglected issues involving the power of emotions and sentiments on ... In all, the author, considering the sources at his disposal, does creditably well by drawing attention to.

  14. SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

    International Nuclear Information System (INIS)

    Lamichhane, N; Studenski, M

    2016-01-01

    Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobend block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.

  15. SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

    Energy Technology Data Exchange (ETDEWEB)

    Lamichhane, N; Studenski, M [University of Miami, Miami, FL (United States)

    2016-06-15

    Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobend block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.

  16. Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

    Science.gov (United States)

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-01-01

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

  17. Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

    Science.gov (United States)

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-10-11

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

  18. The Philips QL-lamp : modelling and comparison with experiments

    NARCIS (Netherlands)

    Benoij, D.A.; Heuvel, van den J.; Jonkers, J.; Mullen, van der J.J.A.M.

    1996-01-01

    Summary form only given. The Philips QL lightsource is a low pressure inductively coupled RF discharge. The main advantage of this system is the fact that it contains no electrodes so that the lifetime is longer. A characteristic feature is that the induction coil with a ferrite core is located at

  19. Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858).

    Science.gov (United States)

    Unciuleac, Mihaela-Carmen; Smith, Paul C; Shuman, Stewart

    2016-05-15

    AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a Mycobacterium smegmatis AAA protein Msm0858, the ortholog of Mycobacterium tuberculosis Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer. Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a

  20. Pareto front analysis of 6 and 15 MV dynamic IMRT for lung cancer using pencil beam, AAA and Monte Carlo

    DEFF Research Database (Denmark)

    Ottosson, R O; Hauer, Anna Karlsson; Behrens, C.F.

    2010-01-01

    to normal tissue sparing weighted. All optimized treatment plans were calculated using three different calculation algorithms (PBC, AAA and MC). In order to study the influence of motion, two virtual lung phantoms were created. The idea was to mimic two different situations: one where the GTV is located...... centrally in the PTV and another where the GTV was close to the edge of the PTV. PBC is in poor agreement with MC and AAA for all cases and treatment plans. AAA overestimates the dose, compared to MC. This effect is more pronounced for 15 than 6MV. AAA and MC both predict similar perturbations in dose...... distributions when moving the GTV to the edge of the PTV. PBC, however, predicts results contradicting those of AAA and MC. This study shows that PB-based dose calculation algorithms are clinically insufficient for patient geometries involving large density inhomogeneities. AAA is in much better agreement...

  1. Interview with Dr. Philip Stone, executive director of the Institute for Dark Tourism Research

    OpenAIRE

    BAILLARGEON, Taïka

    2016-01-01

    Dr. Philip Stone is the executive director of the Institute for Dark Tourism Research. Founded in 2012 and based at the University of Central Lancashire (UCLan), England, the iDTR largely contributes to scientific research on Dark Tourism while offering guidance to industry practitioners and collaborating with the media. In 2009, along with his colleague Richard Sharpley, Philip Stone published The Darker Side of Travel: The Theory and Practice of Dark Tourism. This book has become one of the...

  2. AAA application in diagnosis exams in a large public hospital, RS, Brazil

    International Nuclear Information System (INIS)

    Bacelar, A.; Ferret, A.A.; Vanni, S.; Galhardi, M.P.; Lykawka, R.

    2013-01-01

    Objective: the initiative AAA - Awareness , Appropriateness and Audit , promotes consciousness ( Awareness) , fitness ( Appropriateness ) and Audit ( Audit) . This paper analyzes the application of the concept in the AAA requests and justifications examinations using ionizing radiation within a large public hospital. Materials and methods: we collected and analyzed data between the years 2011 and 2012, concerning the number of exams performed with the use of radiation and their justifications. After, we sought to raise awareness of the clinical team through training on the risks and benefits of the various modalities of the radiology department and the need to justify the use of ionizing radiation on health. After the data were collected again of test requests for verification of the effectiveness of training. Results: the mean requests that need to be appropriate to the AAA in the last quarter of 2011 was 75 % lower than the average demands of the first quarter, matched against the last two months of 2012 increased by up to four times the number requests that require improvements in relation to the excellent results obtained in July 2012. Conclusion: it is shown in this paper the need of implementing this initiative AAA continuously added to the clinical staff awareness about the risk of the use of ionizing radiation, the appropriateness of the requests of these tests , as well as the control of this process in order to optimize use of ionizing radiation on health

  3. Effects of doping and bias voltage on the screening in AAA-stacked trilayer graphene

    Science.gov (United States)

    Mohammadi, Yawar; Moradian, Rostam; Shirzadi Tabar, Farzad

    2014-09-01

    We calculate the static polarization of AAA-stacked trilayer graphene (TLG) and study its screening properties within the random phase approximation (RPA) in all undoped, doped and biased regimes. We find that the static polarization of undoped AAA-stacked TLG is a combination of the doped and undoped single-layer graphene static polarization. This leads to an enhancement of the dielectric background constant along a Thomas-Fermi screening with the Thomas-Fermi wave vector which is independent of carrier concentrations and a 1/r3 power law decay for the long-distance behavior of the screened Coulomb potential. We show that effects of a bias voltage can be taken into account by a renormalization of the interlayer hopping energy to a new bias-voltage-dependent value, indicating screening properties of AAA-stacked TLG can be tuned electrically. We also find that screening properties of doped AAA-stacked TLG, when μ exceeds √{2}γ, are similar to that of doped SLG only depending on doping. While for μ<√{2}γ, its screening properties are combination of SLG and AA-stacked bilayer graphene screening properties and they are determined by doping and the interlayer hopping energy.

  4. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters

    International Nuclear Information System (INIS)

    Bufacchi, Antonella; Nardiello, Barbara; Capparella, Roberto; Begnozzi, Luisa

    2013-01-01

    Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. In the prostate plans, the AAA predicted lower NTCP value (NTCP AAA ) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCP AAA , that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCP PBC ’s ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCP AAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCP PBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCP AAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCP AAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the

  5. Validation of a Piezoelectric Sensor Array-Based Device for Measurement of Carotid-Femoral Pulse Wave Velocity: The Philips Prototype.

    Science.gov (United States)

    Xu, Shao-Kun; Hong, Xiang-Fei; Cheng, Yi-Bang; Liu, Chang-Yuan; Li, Yan; Yin, Bin; Wang, Ji-Guang

    2018-03-01

    Multiple piezoelectric pressure mechanotransducers topologized into an array might improve efficiency and accuracy in collecting arterial pressure waveforms for measurement of pulse wave velocity (PWV). In the present study, we validated a piezoelectric sensor array-based prototype (Philips) against the validated and clinically widely used Complior device (Alam Medical). We recruited 33 subjects with a wide distribution of PWV. For the validation, PWV was measured sequentially with the Complior device (four times) and the Philips prototype (three times). With the 99 paired PWV values, we investigated the agreement between the Philips prototype and the Complior device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices. The correlation coefficient for PWV measured with the two devices was 0.92 ( p prototype slightly overestimated PWV by 0.24 (± 2 standard deviations, ± 1.91) m/s, especially when PWV was high. The correlation coefficient between the difference and the average of the Philips and Complior measurements was 0.21 ( p = 0.035). Nonetheless, they had similar determinants. Age, mean arterial pressure, and sex altogether explained 81.6 and 83.9% of the variance of PWV values measured with the Philips prototype and Complior device, respectively. When the two extremes of the three PWV values measured with the Philips prototype and the Complior device were investigated, the coefficients of variation were 8.26 and 3.26%, respectively. Compared with the Complior device, the Philips prototype had similar accuracy, determinants, and reproducibility in measuring PWV.

  6. Norms for multivariate diagnosis of nutrient imbalance in the East African highland bananas (musa spp.aaa)

    NARCIS (Netherlands)

    Wairegi, L.; Asten, van P.

    2011-01-01

    Despite low yields and soil fertility problems, fertilizer use in the East African Highland banana (AAA-EA) production is absent. High fertilizer costs increase the need for site-specific fertilizer recommendations that address deficiencies. This study aimed to derive and compare norms for AAA-EA

  7. Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

    OpenAIRE

    Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

    2015-01-01

    Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have t...

  8. SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

    Science.gov (United States)

    Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

    2018-01-01

    Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of the SMYD2 promoter may be linked with decreased SMYD2 expression in disease pathobiology. In

  9. Kotler : teiste inimeste arvamust usutakse enam kui meediat / Philip Kotler

    Index Scriptorium Estoniae

    Kotler, Philip

    2007-01-01

    Philip Kotler vastab küsimustele, millised faktorid mõjutasid tänapäevase turunduse kujundamist, millised vahendid on kasulikud tarbijate leidmiseks, meelitamiseks ja hoidmiseks ning milline on tema arvamus selle kohta, et internetti ja sotsiaalseid võrgustikke nähakse kui tuleviku turundusvahendeid

  10. Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer

    International Nuclear Information System (INIS)

    Tsuruta, Yusuke; Nakata, Manabu; Higashimura, Kyoji; Nakamura, Mitsuhiro; Matsuo, Yukinori; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro

    2014-01-01

    Purpose: To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. Methods: Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. Results: The results from AXB and XVMC agreed with measurements within ±3.0% for the lung-equivalent phantom with a 6 × 6 cm 2 field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ±3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124–358 s), 66.1 ± 16.0 s (range, 42–94 s), and 6.7 ± 1.1 s (range, 5–9 s) for XVMC, AXB, and AAA, respectively. Conclusions: In the phantom

  11. Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

    Science.gov (United States)

    Tsuruta, Yusuke; Nakata, Manabu; Nakamura, Mitsuhiro; Matsuo, Yukinori; Higashimura, Kyoji; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro

    2014-08-01

    To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. In the phantom evaluations, AXB and XVMC agreed better with

  12. Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome.

    Science.gov (United States)

    Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-01-05

    The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA 1 and Peak AAA 2 differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH +) of mass 343.239Da (Da), corresponding to a molecular formula of C 21 H 30 N 2 O 2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak AAA 1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA 2 was determined to be a condensation product of L-Trp with decanoic acid, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

    Science.gov (United States)

    Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

    2013-06-14

    The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

  14. Structure and evolution of N-domains in AAA metalloproteases.

    Science.gov (United States)

    Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

    2015-02-27

    Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

  15. Application of isotopic information for estimating parameters in Philip infiltration model

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2016-10-01

    Full Text Available Minimizing parameter uncertainty is crucial in the application of hydrologic models. Isotopic information in various hydrologic components of the water cycle can expand our knowledge of the dynamics of water flow in the system, provide additional information for parameter estimation, and improve parameter identifiability. This study combined the Philip infiltration model with an isotopic mixing model using an isotopic mass balance approach for estimating parameters in the Philip infiltration model. Two approaches to parameter estimation were compared: (a using isotopic information to determine the soil water transmission and then hydrologic information to estimate the soil sorptivity, and (b using hydrologic information to determine the soil water transmission and the soil sorptivity. Results of parameter estimation were verified through a rainfall infiltration experiment in a laboratory under rainfall with constant isotopic compositions and uniform initial soil water content conditions. Experimental results showed that approach (a, using isotopic and hydrologic information, estimated the soil water transmission in the Philip infiltration model in a manner that matched measured values well. The results of parameter estimation of approach (a were better than those of approach (b. It was also found that the analytical precision of hydrogen and oxygen stable isotopes had a significant effect on parameter estimation using isotopic information.

  16. Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

    Science.gov (United States)

    Saffert, Paul; Enenkel, Cordula; Wendler, Petra

    2017-01-01

    Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

  17. Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

    Science.gov (United States)

    Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

    1996-08-01

    Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

  18. Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

    Science.gov (United States)

    Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

    2014-05-01

    The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. PWA90 Workshop : Marking the Scientific Accomplishments of Philip W. Anderson

    CERN Document Server

    Coleman, PIers; Kotliar, Gabi; Ong, Phuan; Stein, Daniel L; Yu, Clare; PWA90 : a lifetime of emergence

    2016-01-01

    In a remarkable career spanning more than six decades, Philip W Anderson has made many fundamental contributions to physics. As codified in his oft-quoted phrase "More is Different", Anderson has been the most forceful and persuasive proponent of the radical, but now ubiquitous, viewpoint of emergent phenomena: truly fundamental concepts that can and do emerge from studies of Nature at each layer of complexity or energy scale. Anderson's ideas have also extended deeply into other areas of physics, including the Anderson–Higgs mechanism and the dynamics of pulsars. PWA90: A Lifetime of Emergence is a volume of original scientific essays and personal reminiscences of Philip W Anderson by experts in the field, that were presented as part of "PWA90: Emergent Frontiers of Condensed Matter" meeting held at Princeton in December 2013 to highlight Anderson's contributions to physics.

  20. Philip II’s Quest. The Appointment of Governors-General during the Dutch Revolt (1559-1598

    Directory of Open Access Journals (Sweden)

    V. Soen

    2011-01-01

    Full Text Available Philip II’s Quest: The Appointment of Governors-General during the Dutch Revolt (1559-1598Recent historiographical studies have presented the Habsburg appointment of governors-general during the Dutch Revolt as the outcome of factional infighting at the Spanish Court. While this so-called ‘faction model’ has yielded new insights, it also raises a number of problems. Firstly, in the new model, the role of the dynasty is unduly relegated to the background – even though Philip II’s appointment decisions were mainly driven by dynastic considerations. Secondly, the power struggle at the Spanish Court was not only a conflict between court factions, but also between noble houses vying for prestige and trying to secure positions for their offspring. Thirdly, there is an excessive focus on the Spanish Court, while the feuds between noble houses in the Low Countries also played a role in the interim appointments made during the Revolt. Finally, Philip II always looked for the most suitable candidate in terms of administration and warfare during the Dutch Revolt, in accordance with the constraints of the composite Spanish monarchy. Only the combination of these four (frequently contradictory motives reveals how Philip II’s appointment of governors can be seen as a quest for the right man or woman in the right place.

  1. Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

    Science.gov (United States)

    Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

    2011-10-01

    Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

  2. Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

    Science.gov (United States)

    Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

    2015-08-01

    Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

  3. SU-F-T-622: Comparative Analysis of Pencil Beam and Anisotropic Analytical Algorithm (AAA) for Stereotactic Body Radiation Therapy (SBRT) of Thoracic Spine

    Energy Technology Data Exchange (ETDEWEB)

    Badkul, R; Nicolai, W; Pokhrel, D; Jiang, H; Wang, F; Lominskac, C [University of Kansas Medical Center, Kansas City, KS (United States); Ramanjappa, T [S. K. University, Anantapur, AP (India)

    2016-06-15

    Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volume parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.

  4. Creating the "desired mindset": Philip Morris's efforts to improve its corporate image among women.

    Science.gov (United States)

    McDaniel, Patricia A; Malone, Ruth E

    2009-01-01

    Through analysis of tobacco company documents, we explored how and why Philip Morris sought to enhance its corporate image among American women. Philip Morris regarded women as an influential political group. To improve its image among women, while keeping tobacco off their organizational agendas, the company sponsored women's groups and programs. It also sought to appeal to women it defined as "active moms" by advertising its commitment to domestic violence victims. It was more successful in securing women's organizations as allies than active moms. Increasing tobacco's visibility as a global women's health issue may require addressing industry influence.

  5. Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

    Directory of Open Access Journals (Sweden)

    Ferrell Robert E

    2011-01-01

    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM database. Methods Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22 were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. Results Several SNPs were nominally associated with AAA (p CEBPG, peptidase D (PEPD, and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. Conclusions Association testing

  6. Working to make an image: an analysis of three Philip Morris corporate image media campaigns.

    Science.gov (United States)

    Szczypka, Glen; Wakefield, Melanie A; Emery, Sherry; Terry-McElrath, Yvonne M; Flay, Brian R; Chaloupka, Frank J

    2007-10-01

    To describe the nature and timing of, and population exposure to, Philip Morris USA's three explicit corporate image television advertising campaigns and explore the motivations behind each campaign. Analysis of television ratings from the largest 75 media markets in the United States, which measure the reach and frequency of population exposure to advertising; copies of all televised commercials produced by Philip Morris; and tobacco industry documents, which provide insights into the specific goals of each campaign. Household exposure to the "Working to Make a Difference: the People of Philip Morris" averaged 5.37 ads/month for 27 months from 1999-2001; the "Tobacco Settlement" campaign averaged 10.05 ads/month for three months in 2000; and "PMUSA" averaged 3.11 ads/month for the last six months in 2003. The percentage of advertising exposure that was purchased in news programming in order to reach opinion leaders increased over the three campaigns from 20%, 39% and 60%, respectively. These public relations campaigns were designed to counter negative images, increase brand recognition, and improve the financial viability of the company. Only one early media campaign focused on issues other than tobacco, whereas subsequent campaigns have been specifically concerned with tobacco issues, and more targeted to opinion leaders. The size and timing of the advertising buys appeared to be strategically crafted to maximise advertising exposure for these population subgroups during critical threats to Philip Morris's public image.

  7. Philip Morris's website and television commercials use new language to mislead the public into believing it has changed its stance on smoking and disease.

    Science.gov (United States)

    Friedman, Lissy C

    2007-12-01

    This paper analyses Philip Morris's evolving website and the legal strategies employed in its creation and dissemination. Internal tobacco documents were searched and examined and their substance verified and triangulated using media accounts, legal and public health research papers, and visits to Philip Morris's website. Various drafts of website language, as well as informal discussion of the website's creation, were located in internal Philip Morris documents. I compared website statements pertaining to Philip Morris's stance on cigarette smoking and disease with statements made in tobacco trials. Philip Morris created and disseminated its website's message that it agreed that smoking causes disease and is addictive in an effort to sway public opinion, while maintaining in a litigation setting its former position that it cannot be proved that smoking causes disease or is addictive. Philip Morris has not changed its position on smoking and health or addiction in the one arena where it has the most to lose-in the courtroom, under oath.

  8. Patient and Aneurysm Characteristics Predicting Prolonged Length of Stay After Elective Open AAA Repair in the Endovascular Era.

    Science.gov (United States)

    Casillas-Berumen, Sergio; Rojas-Miguez, Florencia A; Farber, Alik; Komshian, Sevan; Kalish, Jeffrey A; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

    2018-01-01

    Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.

  9. Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice

    International Nuclear Information System (INIS)

    Yang Yan; Mahaffey, Connie L.; Berube, Nathalie; Nystuen, Arne; Frankel, Wayne N.

    2005-01-01

    The mouse fidget mutation is an autosomal recessive mutation that renders reduced or absent semicircular canals, microphthalmia, and various skeletal abnormalities to affected mice. We previously identified the defective gene which encodes fidgetin, a new member of the ATPases associated with diverse cellular activities (AAA proteins). Here, we report on the subcellular localization of fidgetin as well as that of two closely related proteins, fidgetin-like 1 and fidgetin-like 2. Epitope-tagging and immunostaining revealed that both fidgetin and fidgetin-like 2 were predominantly localized to the nucleus, whereas fidgetin-like 1 was both nuclear and cytoplasmic. Furthermore, deletion studies identified a putative bipartite nuclear localization signal in the middle portion of the fidgetin protein. Since AAA proteins are known to form functional hetero- or homo-hexamers, we used reciprocal immunoprecipitation to examine the potential interaction among these proteins. We found that fidgetin interacted with itself and this specific interaction was abolished when either the N- or C-terminus of the protein was truncated. Taken together, our results suggest that fidgetin is a nuclear AAA-family protein with the potential to form homo-oligomers, thus representing the first step towards the elucidation of fidgetin's cellular function and the disease mechanism in fidget mutant mice

  10. From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

    Science.gov (United States)

    Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

    2016-06-01

    When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when transitioning from AAA to AXB, no significant change to existing prescription protocols is expected. As most of the clinical experience is dose-to-water based and calibration protocols and clinical trials are

  11. How Philip Morris built Marlboro into a global brand for young adults: implications for international tobacco control.

    Science.gov (United States)

    Hafez, N; Ling, P M

    2005-08-01

    To describe Philip Morris' global market research and international promotional strategies targeting young adults. Analysis of previously secret tobacco industry documents. Philip Morris pursued standardised market research and strategic marketing plans in different regions throughout the world using research on young adults with three principle foci: lifestyle/psychographic research, brand studies, and advertising/communication effectiveness. Philip Morris identified core similarities in the lifestyles and needs of young consumers worldwide, such as independence, hedonism, freedom, and comfort. In the early 1990s Philip Morris adopted standardised global marketing efforts, creating a central advertising production bank and guidelines for brand images and promotions, but allowing regional managers to create regionally appropriate individual advertisements. Values and lifestyles play a central role in the global marketing of tobacco to young adults. Worldwide counter marketing initiatives, coupled with strong, coherent global marketing policies such as the Framework Convention on Tobacco Control, are needed to break associations between young adult values and tobacco brands. As globalisation promotes the homogenisation of values and lifestyles, tobacco control messages that resonate with young adults in one part of the world may appeal to young adults in other countries. Successful tobacco control messages that appeal to young people, such as industry denormalisation, may be expanded globally with appropriate tailoring to appeal to regional values.

  12. Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

    Science.gov (United States)

    Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

    2017-09-07

    How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

    Science.gov (United States)

    Ambler, Graeme K; Gohel, Manjit S; Mitchell, David C; Loftus, Ian M; Boyle, Jonathan R

    2015-01-01

    Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  14. Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

    Science.gov (United States)

    Rampello, Anthony J; Glynn, Steven E

    2017-03-24

    The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Leadership style and entrepreneurial change: the Centurion operation at Philips Electronics

    NARCIS (Netherlands)

    Karsten, L.; Keulen, S.; Kroeze, R.; Peters, R.

    2009-01-01

    Purpose - This paper aims to look at the role of the top and middle management of the Philips organization during the transition from one type of organizational change to another in the 1990s and the role the history of the organisation played in this process. Design/methodology/approach - The paper

  16. Leadership style and entrepreneurial change : The Centurion operation at Philips Electronics

    NARCIS (Netherlands)

    Karsten, Luchien; Keulen, Sjoerd; Kroeze, Ronald; Peters, Rik

    2009-01-01

    Purpose - This paper aims to look at the role of the top and middle management of the Philips organization during the transition from one type of organizational change to another in the 1990s and the role the history of the organisation played in this process. Design/methodology/approach - The paper

  17. Leadership style and entrepreneurial change: The Centurion operation at Philips Electronics

    NARCIS (Netherlands)

    Kroeze, D.B.R.; Karsten, L.; Keulen, S.J.; Peters, R.G.P.

    2009-01-01

    Purpose - This paper aims to look at the role of the top and middle management of the Philips organization during the transition from one type of organizational change to another in the 1990s and the role the history of the organisation played in this process. Design/methodology/approach - The paper

  18. Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

    Science.gov (United States)

    Dasari, Suvarna; Kölling, Ralf

    2016-07-01

    We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

  19. Characteristics of Philips SL-20 linear accelerator used for stereotactic radiosurgery/radiotherapy

    International Nuclear Information System (INIS)

    D'Souza, Harold; Ganesh, T.; Joshi, R.C.; Julka, P.K.; Rath, G.K.; Chander, Subhash; Pant, G.S.

    2002-01-01

    Commissioning of a stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) facility on a modified linear accelerator requires validation of mechanical parameters and establishment of parameters, such as tissue maximum ratio (TMR), relative output factors (OF), and off axis ratios (OAR). The mechanical and beam characteristics of Philips SL-20 linear accelerator modified for SRS/SRT were evaluated and presented. The SRS/SRT procedure carried on Philips SL-20 linear accelerator with Brown-Robert-Wells (BRW) and relocatable Gill-Thomas-Cosman (GTC) head frames along with the Radionics planning system was evaluated. The tertiary collimator consists of the actual treatment cones and their sizes vary from 12.5 mm to 40 mm diameter. The alignment of the auxillary collimator axis with mechanical axes and stability of the isocenter of Philips SL-20 machine was evaluated using Iso-Align device and mechanical isocenter standard (MIS). All the mechanical errors of the linear accelerator were within 1 mm, except the stability of the isocenter while rotating the couch. Alignment of auxiliary collimator axis with the central axis, gantry and couch axes were achieved. The TMR, OF and OAR for 6 MV x-rays from Philips SL-20 linear accelerator for different cone sizes were deduced using a Multidata water phantom with 0.015 cc ion chamber. The difference between 50% width of profiles in two major axes (x and y) were within ± 0.4 mm. The cone dimensions were accurate up to 0.7 mm. The penumbra width for different cones varies from 3.1 mm to 3.5 mm. Dose linearity of the monitoring system was ≤ 1% above 5 MU. The mechanical and beam characteristics including dose linearity of the SL-20 machine are presented. The beam characteristics of this machine are comparable with the other modified linear accelerators for SRS/SRT. The shift of isocenter during rotation of couch can be nullified by fine adjusting laser target localizing frame to the laser position using micrometer screws

  20. Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

    Science.gov (United States)

    Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

    2017-08-01

    The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  1. A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

    Science.gov (United States)

    Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

    2018-02-05

    AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Monte Carlo evaluation of the AAA treatment planning algorithm in a heterogeneous multilayer phantom and IMRT clinical treatments for an Elekta SL25 linear accelerator

    International Nuclear Information System (INIS)

    Sterpin, E.; Tomsej, M.; Smedt, B. de; Reynaert, N.; Vynckier, S.

    2007-01-01

    The Anisotropic Analytical Algorithm (AAA) is a new pencil beam convolution/superposition algorithm proposed by Varian for photon dose calculations. The configuration of AAA depends on linear accelerator design and specifications. The purpose of this study was to investigate the accuracy of AAA for an Elekta SL25 linear accelerator for small fields and intensity modulated radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC) and the measurements in an inhomogeneous phantom simulating lung equivalent tissues and bone ribs. The algorithm was tested under lateral electronic disequilibrium conditions, using small fields (2x2 cm 2 ). Good agreement was generally achieved for depth dose and profiles, with deviations generally below 3% in lung inhomogeneities and below 5% at interfaces. However, the effects of attenuation and scattering close to the bone ribs were not fully taken into account by AAA, and small inhomogeneities may lead to planning errors. Second, AAA and MC were compared for IMRT plans in clinical conditions, i.e., dose calculations in a computed tomography scan of a patient. One ethmoid tumor, one orophaxynx and two lung tumors are presented in this paper. Small differences were found between the dose volume histograms. For instance, a 1.7% difference for the mean planning target volume dose was obtained for the ethmoid case. Since better agreement was achieved for the same plans but in homogeneous conditions, these differences must be attributed to the handling of inhomogeneities by AAA. Therefore, inherent assumptions of the algorithm, principally the assumption of independent depth and lateral directions in the scaling of the kernels, were slightly influencing AAA's validity in inhomogeneities. However, AAA showed a good accuracy overall and a great ability to handle small fields in inhomogeneous media compared to other pencil beam convolution

  3. [Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

    Science.gov (United States)

    Biros, E; Staffa, R

    2011-12-01

    Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the

  4. SU-E-T-122: Anisotropic Analytical Algorithm (AAA) Vs. Acuros XB (AXB) in Stereotactic Treatment Planning

    International Nuclear Information System (INIS)

    Mynampati, D; Scripes, P Godoy; Kuo, H; Yaparpalvi, R; Tome, W

    2015-01-01

    Purpose: To evaluate dosimetric differences between superposition beam model (AAA) and determinant photon transport solver (AXB) in lung SBRT and Cranial SRS dose computations. Methods: Ten Cranial SRS and ten Lung SBRT plans using Varian, AAA -11.0 were re-planned using Acuros -XB-11.0 with fixed MU. 6MV photon Beam model with HD120-MLC used for dose calculations. Four non-coplanar conformal arcs used to deliver 21Gy or 18Gy to SRS targets (0.4 to 6.2cc). 54Gy (3Fractions) or 50Gy (5Fractions) was planned for SBRT targets (7.3 to 13.9cc) using two VAMT non-coplanar arcs. Plan comparison parameters were dose to 1% PTV volume (D1), dose to 99% PTV volume( D99), Target mean (Dmean), Conformity index (ratio of prescription isodose volume to PTV), Homogeneity Index [ (D2%-D98%)/Dmean] and R50 (ratio of 50% of prescription isodose volume to PTV). OAR parameters were Brain volume receiving 12Gy dose (V12Gy) and maximum dose (D0.03) to Brainstem for SRS. For lung SBRT, maximum dose to Heart and Cord, Mean lung dose (MLD) and volume of lung receiving 20Gy (V20Gy) were computed. PTV parameters compared by percentage difference between AXB and AAA parameters. OAR parameters and HI compared by absolute difference between two calculations. For analysis, paired t-test performed over the parameters. Results: Compared to AAA, AXB SRS plans have on average 3.2% lower D99, 6.5% lower CI and 3cc less Brain-V12. However, AXB SBRT plans have higher D1, R50 and Dmean by 3.15%, 1.63% and 2.5%. For SRS and SBRT, AXB plans have average HI 2 % and 4.4% higher than AAA plans. In both techniques, all other parameters vary within 1% or 1Gy. In both sets only two parameters have P>0.05. Conclusion: Even though t-test results signify difference between AXB and AAA plans, dose differences in dose estimations by both algorithms are clinically insignificant

  5. An Information Model for Product Development : A Case Study at PHILIPS Shavers

    NARCIS (Netherlands)

    Jauregui Becker, Juan Manuel; Wits, Wessel Willems

    2013-01-01

    This paper presents an investigation into the development of an information model to support the Product Development Process (PDP) of shaving devices at PHILIPS. Firstly, challenges of the PDP were identified by carrying out interviews with several systems engineers and product architects. It was

  6. SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA & CCC Algorithms for VMAT Technique.

    Science.gov (United States)

    Kathirvel, M; Subramanian, V Sai; Arun, G; Thirumalaiswamy, S; Ramalingam, K; Kumar, S Ashok; Jagadeesh, K

    2012-06-01

    To dosimetrically validate AcurosXB algorithm for Volumetric Modulated Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms. AcurosXB dose calculation algorithm is available with Varian Eclipse treatment planning system (V10). It uses grid-based Boltzmann equation solver to predict dose precisely in lesser time. This study was made to realize algorithms ability to predict dose accurately as its delivery for which five clinical cases each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification plans were created on multicube phantom with iMatrixx-2D detector array and then dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and the same were delivered onto CLINAC-iX treatment machine. Delivered dose was captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference to quantify the agreement between AcurosXB calculation algorithm against previously validated AAA and CCC algorithm. Gamma evaluation was performed with clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro-I'MRT software. Plans were evaluated in terms of correlation coefficient, quantitative area gamma and average gamma. Study shows good agreement between mean correlation 0.9979±0.0012, 0.9984±0.0009 & 0.9979±0.0011 for AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to be 98.80±1.04, 98.14±2.31, 98.08±2.01 and 2mm/2% was found to be 93.94±3.83, 87.17±10.54 & 92.36±5.46 for AAA, CCC & Acuros respectively. Mean average gamma for 3mm/3% was 0.26±0.07, 0.42±0.08, 0.28±0.09 and 2mm/2% was found to be 0.39±0.10, 0.64±0.11, 0.42±0.13 for AAA, CCC & Acuros respectively. This study demonstrated that the AcurosXB algorithm had a good agreement with the AAA & CCC in terms of dose prediction. In conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative to AAA

  7. From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium

    International Nuclear Information System (INIS)

    Zifoyda, Jackson M.; Challens, Cameron H.C.; Hsieh, Wen-Long

    2016-01-01

    When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when transitioning

  8. Dialéctica material Donald Judd y Philip Johnson

    Directory of Open Access Journals (Sweden)

    María Teresa Muñoz

    2016-05-01

    Full Text Available Resumen El objetivo de este escrito es examinar cómo se plantea una cierta dialéctica material en el conjunto llamado la Mansana de Chinati, construido por el escultor Donald Judd en la ciudad de Marfa, Texas, a partir del año 1974, comparándolo con las dos viviendas que realiza el arquitecto Philip Johnson en su propiedad de New Canaan, Connecticut, en torno al año 1950. Tanto en New Canaan como en la Mansana de Chinati existe una  oposición, una dialéctica, entre una arquitectura industrial y otra artesana, tanto Philip Johnson como Donald Judd consideran que existe una arquitectura principal, la realizada con materiales y técnicas industriales, y otra subalterna o de servicio, la construida con piezas de arcilla y técnicas artesanales. Esta segunda arquitectura encarnará las cualidades asociadas con la pobreza, la abundancia material y la clausura espacial. Sin  embargo, esta exhibición de pobreza no tiene como fin los propios edificios domésticos construidos artesanalmente, ya sea con adobe o con ladrillo, sino que estará al servicio de esa otra arquitectura, construida con técnicas industriales, a la que se exige renunciar a la comodidad y el confort o cuando menos ocultarlos bajo la forma de una radical austeridad.

  9. Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

    Science.gov (United States)

    Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

    2015-04-10

    The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

    Science.gov (United States)

    Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

    2017-07-14

    Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

  11. m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

    Science.gov (United States)

    Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

    2018-05-01

    For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

  12. ARTIST (Asian regional tobacco industry scientist team): Philip Morris' attempt to exert a scientific and regulatory agenda on Asia.

    Science.gov (United States)

    Tong, E K; Glantz, S A

    2004-12-01

    To describe how the transnational tobacco industry has collaborated with local Asian tobacco monopolies and companies to promote a scientific and regulatory agenda. Analysis of previously secret tobacco industry documents. Transnational tobacco companies began aggressively entering the Asia market in the 1980s, and the current tobacco industry in Asia is a mix of transnational and local monopolies or private companies. Tobacco industry documents demonstrate that, in 1996, Philip Morris led an organisation of scientific representatives from different tobacco companies called the Asian Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia. ARTIST was initially a vehicle for PM's strategies against anticipated calls for global smoke-free areas from a World Health Organization secondhand smoke study. ARTIST evolved through 2001 into a forum to present scientific and regulatory issues faced primarily by Philip Morris and other transnational tobacco companies. Philip Morris' goal for the organisation became to reach the external scientific and public health community and regulators in Asia. The Asian tobacco industry has changed from an environment of invasion by transnational tobacco companies to an environment of participation with Philip Morris' initiated activities. With this participation, tobacco control efforts in Asia face new challenges as Philip Morris promotes and integrates its scientific and regulatory agenda into the local Asian tobacco industry. As the local Asian tobacco monopolies and companies can have direct links with their governments, future implementation of effective tobacco control may be at odds with national priorities.

  13. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

    Science.gov (United States)

    Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

    2018-01-29

    Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

  14. Patient-specific AAA wall stress analysis: 99-percentile versus peak stress

    NARCIS (Netherlands)

    Speelman, L.; Bosboom, E.M.H.; Schurink, G.W.H.; Hellenthal, F.A.M.V.I.; Buth, J.; Breeuwer, M.; Jacobs, M.J.; Vosse, van de F.N.

    2008-01-01

    Objective Biomechanically, rupture of an Abdominal Aortic Aneurysm (AAA) occurs when the stress acting on the wall due to the blood pressure, exceeds the strength of the wall. Peak wall stress estimations, based on CT reconstruction, may be prone to observer variation. This study focuses on the

  15. Muusika ilma kuulajata pole palju väärt / Philip Glass ; interv. Immo Mihkelson

    Index Scriptorium Estoniae

    Glass, Philip, 1937-

    2003-01-01

    Philip Glass ja tema ansambel esitavad 2. detsembril PÖFFil oma filmimuusika Godfrey Reggio filmile "Koyaanisqatsi" selle linastusel Tallinna linnahallis. Helilooja räägib oma muusika missioonist, oma lava- ja filmimuusikast

  16. In-depth study of single photon time resolution for the Philips digital silicon photomultiplier

    International Nuclear Information System (INIS)

    Liu, Z.; Pizzichemi, M.; Ghezzi, A.; Paganoni, M.; Gundacker, S.; Auffray, E.; Lecoq, P.

    2016-01-01

    The digital silicon photomultiplier (SiPM) has been commercialised by Philips as an innovative technology compared to analog silicon photomultiplier devices. The Philips digital SiPM, has a pair of time to digital converters (TDCs) connected to 12800 single photon avalanche diodes (SPADs). Detailed measurements were performed to understand the low photon time response of the Philips digital SiPM. The single photon time resolution (SPTR) of every single SPAD in a pixel consisting of 3200 SPADs was measured and an average value of 85 ps full width at half maximum (FWHM) was observed. Each SPAD sends the signal to the TDC with different signal propagation time, resulting in a so called trigger network skew. This distribution of the trigger network skew for a pixel (3200 SPADs) has been measured and a variation of 50 ps FWHM was extracted. The SPTR of the whole pixel is the combination of SPAD jitter, trigger network skew, and the SPAD non-uniformity. The SPTR of a complete pixel was 103 ps FWHM at 3.3 V above breakdown voltage. Further, the effect of the crosstalk at a low photon level has been studied, with the two photon time resolution degrading if the events are a combination of detected (true) photons and crosstalk events. Finally, the time response to multiple photons was investigated.

  17. Instrumental parameters' determination in a fluorescences X-ray Philips PW 1400 equipment

    International Nuclear Information System (INIS)

    Martinez, J.M.; Fasio, I.; Baronio, N.; Viola, M.

    1987-01-01

    The instrumental parameters of a Philips PW 1400 equipment wavelengths dispersive are determined; fundamentally, those related to the equipment's accuracy (stability at a very short, short and long term drift) as well as to those related to the detection system (dead time, detector's cleaning and detection limit). (S.M.) [es

  18. Characterization of ATPase activity of the AAA ARC from Bifidobacterium longum subsp. infantis.

    Science.gov (United States)

    Guzmán-Rodríguez, Mabel; de la Rosa, Ana Paulina Barba; Santos, Leticia

    2015-01-01

    Bifidobacteria are considered to be probiotics that exist in the large intestine and are helpful to maintain human health. Oral administration of bifidobacteria may be effective in improving the intestinal flora and environment, stimulating the immune response and possibly preventing cancer. However, for consistent and positive results, further well-controlled studies are urgently needed to describe the basic mechanisms of this microorganism. Analysis of the proteasome-lacking Bifidobacterium longum genome reveals that it possesses a gene, IPR003593 AAA ATPase core, which codes a 56 kDa protein containing one AAA ATPase domain. Phylogenetic classification made by CLANS, positioned this sequence into the ARC divergent branch of the AAA ATPase family of proteins. N-terminal analysis of the sequence indicates this protein is closely related to other ATPases such as the Rhodococcus erythropolis ARC, Archaeoglobus fulgidus PAN, Mycobacterium tuberculosis Mpa and the human proteasomal Rpt1 subunit. This gene was cloned, the full-length recombinant protein was overexpressed in Escherichia coli, purified as a high-molecular size complex and named Bl-ARC. Enzymatic characterization showed that Bl-ARC ATPase is active, Mg(+2)-dependent and sensitive to N-ethylmaleimide. Gene organization positions bl-arc in a region flanked by a cluster of genes that includes pup, dop and pafA genes. These findings point to a possible function as a chaperone in the degradation pathway via pupylation.

  19. Enhancing the IT Infrastructure at Saint Philip's Hospital: Point-of-Care Solutions

    Science.gov (United States)

    Naydenova, Iva; White, Bruce

    2013-01-01

    Healthcare has become a rapidly changing field. With the introduction of value-based purchasing to determine reimbursement of Medicare providers based on the quality of care in addition to outcomes in treatment, the environment is becoming ever more competitive. Saint Philip's Hospital is among the largest non-profit hospitals in the nation…

  20. Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

    Science.gov (United States)

    Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

    2017-11-22

    Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

  1. The ATPase of the phi29 DNA packaging motor is a member of the hexameric AAA+ superfamily.

    Science.gov (United States)

    Schwartz, Chad; De Donatis, Gian Marco; Fang, Huaming; Guo, Peixuan

    2013-08-15

    The AAA+ superfamily of proteins is a class of motor ATPases performing a wide range of functions that typically exist as hexamers. The ATPase of phi29 DNA packaging motor has long been a subject of debate in terms of stoichiometry and mechanism of action. Here, we confirmed the stoichiometry of phi29 motor ATPase to be a hexamer and provide data suggesting that the phi29 motor ATPase is a member of the classical hexameric AAA+ superfamily. Native PAGE, EMSA, capillary electrophoresis, ATP titration, and binomial distribution assay show that the ATPase is a hexamer. Mutations in the known Walker motifs of the ATPase validated our previous assumptions that the protein exists as another member of this AAA+ superfamily. Our data also supports the finding that the phi29 DNA packaging motor uses a revolution mechanism without rotation or coiling (Schwartz et al., this issue). Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  2. AAAS Communicating Science Program: Reflections on Evaluation

    Science.gov (United States)

    Braha, J.

    2015-12-01

    The AAAS Center for Public Engagement (Center) with science builds capacity for scientists to engage public audiences by fostering collaboration among natural or physical scientists, communication researchers, and public engagement practitioners. The recently launched Leshner Leadership Institute empowers cohorts of mid-career scientists to lead public engagement by supporting their networks of scientists, researchers, and practitioners. The Center works closely with social scientists whose research addresses science communication and public engagement with science to ensure that the Communicating Science training program builds on empirical evidence to inform best practices. Researchers ( Besley, Dudo, & Storkdieck 2015) have helped Center staff and an external evaluator develop pan instrument that measures progress towards goals that are suggested by the researcher, including internal efficacy (increasing scientists' communication skills and confidence in their ability to engage with the public) and external efficacy (scientists' confidence in engagement methods). Evaluation results from one year of the Communicating Science program suggest that the model of training yields positive results that support scientists in the area that should lead to greater engagement. This talk will explore the model for training, which provides a context for strategic communication, as well as the practical factors, such as time, access to public engagement practitioners, and technical skill, that seems to contribute to increased willingness to engage with public audiences. The evaluation program results suggest willingness by training participants to engage directly or to take preliminary steps towards engagement. In the evaluation results, 38% of trained scientists reported time as a barrier to engagement; 35% reported concern that engagement would distract from their work as a barrier. AAAS works to improve practitioner-researcher-scientist networks to overcome such barriers.

  3. NASA Astrophysics E/PO Impact: NASA SOFIA AAA Program Evaluation Results

    Science.gov (United States)

    Harman, Pamela; Backman, Dana E.; Clark, Coral; Inverness Research Sofia Aaa Evaluation Team, Wested Sofia Aaa Evaluation Team

    2015-01-01

    SOFIA is an airborne observatory, studying the universe at infrared wavelengths, capable of making observations that are impossible for even the largest and highest ground-based telescopes. SOFIA also inspires the development of new scientific instrumentation and fosters the education of young scientists and engineers.SOFIA is an 80% - 20% partnership of NASA and the German Aerospace Center (DLR), consisting of an extensively modified Boeing 747SP aircraft carrying a reflecting telescope with an effective diameter of 2.5 meters (100 inches). The SOFIA aircraft is based at NASA Armstrong Flight Research Center, Building 703, in Palmdale, California. The Science Program and Outreach Offices are located at NASA Ames Research center. SOFIA is a program in NASA's Science Mission Directorate, Astrophysics Division.Data will be collected to study many different kinds of astronomical objects and phenomena, including star cycles, solar system formation, identification of complex molecules in space, our solar system, galactic dust, nebulae and ecosystems.Airborne Astronomy Ambassador (AAA) Program:The SOFIA Education and Communications program exploits the unique attributes of airborne astronomy to contribute to national goals for the reform of science, technology, engineering, and math (STEM) education, and to elevate public scientific and technical literacy.The AAA effort is a professional development program aspiring to improve teaching, inspire students, and inform the community. To date, 55 educators from 21 states; Cycles 0, 1 and 2; have completed their astronomy professional development and their SOFIA science flight experience. Evaluation has confirmed the program's positive impact on the teacher participants, on their students, and in their communities. The inspirational experience has positively impacted their practice and career trajectory. AAAs have incorporated content knowledge and specific components of their experience into their curricula, and have given

  4. SFM-FDTD analysis of triangular-lattice AAA structure: Parametric study of the TEM mode

    Science.gov (United States)

    Hamidi, M.; Chemrouk, C.; Belkhir, A.; Kebci, Z.; Ndao, A.; Lamrous, O.; Baida, F. I.

    2014-05-01

    This theoretical work reports a parametric study of enhanced transmission through annular aperture array (AAA) structure arranged in a triangular lattice. The effect of the incidence angle in addition to the inner and outer radii values on the evolution of the transmission spectra is carried out. To this end, a 3D Finite-Difference Time-Domain code based on the Split Field Method (SFM) is used to calculate the spectral response of the structure for any angle of incidence. In order to work through an orthogonal unit cell which presents the advantage to reduce time and space of computation, special periodic boundary conditions are implemented. This study provides a new modeling of AAA structures useful for producing tunable ultra-compact devices.

  5. The full automation of a Philips 1220 x-ray spectrometer

    International Nuclear Information System (INIS)

    Austen, C.E.

    1976-01-01

    A Philips 1220 X-ray spectrometer (semi-automatic) was fully automated by the addition of a custom-built automatic sample-loader constructed at the National Institute for Metallurgy and a Texas 980 A mini-computer. The mini-computer was interfaced to the existing control circuits of the X-ray spectrometer through a custom-built logic-circuit unit that controls the automatic sample-loader and X-ray spectrometer on instructions received from the mini-computer. The controlling software is written in BASIC

  6. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    Science.gov (United States)

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-03-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

  7. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    Science.gov (United States)

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-01-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. PMID:24658080

  8. Philip Morris Asia Ltd. v. Australia – abuse of rights in investor-state arbitration / Ulf Linderfalk

    Index Scriptorium Estoniae

    Linderfalk, Ulf

    2017-01-01

    Kohtulahendist Philip Morris Asia Ltd. vs Australia. Õiguste kuritarvitamise doktriinist rahvusvahelises õiguses. Austraalia tubakaseadusest, seadusest tulenevatest piirangutest tubakatoodete pakendamisele, kaubamärgi kasutamise piiramisest tubakatoodete pakendil

  9. Valores Epistêmicos no Naturalismo Normativo de Philip Kitcher

    Directory of Open Access Journals (Sweden)

    Eduardo Salles O. Barra

    2000-06-01

    Full Text Available This paper aims at analyzing Philip Kitcher's naturalistic epistemology, particularly its normative features, which are viewed as a sort of response to negative assessments made by radical naturalists on the plurality of epistemic values. According to them such values are ineffective for normative ends, e.g. theory choice. Differently from that quite excessive evaluation, Kitcher argues rather for explanatory unity as the most important and universal epistemic value. Even though Kitcher's arguments are sound, there remains some serious gaps as regards his attempts; there are also serious doubts about the desirability of achieving such a value.

  10. Metrology at Philip Morris Europe

    Directory of Open Access Journals (Sweden)

    Gualandris R

    2014-12-01

    Full Text Available The importance of the metrology function at Philip Morris Europe (PME, a multinational organisation producing at over 40 sites in the European, Middle Eastern and African Regions is presented. Standardisation of test methods and equipment as well as the traceability of calibration gauges to the same reference gauge are essential in order to obtain comparable results among the various production centers. The metrology function as well as the qualification of instruments and the drafting of test and calibration operating procedures for this region are conducted or co-ordinated by the Research and Development Department in Neuchatel, Switzerland. In this paper the metrology function within PME is presented based on the measurement of the resistance to draw for which the PME R&D laboratory is accredited (ISO/CEI 17025, as both a calibration and a testing laboratory. The following topics are addressed in this paper: traceability of calibration standards to national standards; comparison of results among manufacturing centres; the choice, the budget as well as the computation of uncertainties. Furthermore, some practical aspects related to the calibration and use of the glass multicapillary gauges are discussed.

  11. The Living Tomorrow Project: how Philip Morris has used a Belgian tourist attraction to promote ventilation approaches to the control of second hand smoke

    Science.gov (United States)

    Pilkington, P; Gilmore, A

    2004-01-01

    Study objective: To examine the involvement of Philip Morris in Living Tomorrow 2 and determine the rationale behind its involvement. Design: Research was conducted through a web based search of internal tobacco industry documents made publicly available through litigation. Main results: For approximately €1 000 000 Philip Morris (now Altria) became a co-initiator of Living Tomorrow 2, a tourist complex in Belgium that aims to demonstrate how we will be living in the future. In addition to promoting the company and its grocery products, Philip Morris is using the complex and its website to promote ventilation as a means of accommodating smokers and non-smokers in the indoor environment. Particular emphasis was placed on the bar and restaurant areas. Despite the rationale for its involvement, Philip Morris fails to acknowledge its role as a cigarette manufacturer. As a form of corporate sponsorship Philip Morris thought its involvement could evade any European tobacco advertising ban. Conclusions: Philip Morris is using a tourist attraction to promote its views on control of second hand smoke (SHS) and accommodation of smokers and non-smokers in the indoor environment. However, ventilation does not deal with the health effects of SHS. Policymakers must be cognisant of the devious tactics the industry employs to promote its own agenda, especially in relation to indoor air quality and smoking in public places. Tobacco control legislation should be continually modified and strengthened in response to the changing activities of the tobacco industry as it strives to evade existing legislation and deter the advent of new legislation. PMID:15564621

  12. Pre-Test Analysis of the MEGAPIE Spallation Source Target Cooling Loop Using the TRAC/AAA Code

    International Nuclear Information System (INIS)

    Bubelis, Evaldas; Coddington, Paul; Leung, Waihung

    2006-01-01

    A pilot project is being undertaken at the Paul Scherrer Institute in Switzerland to test the feasibility of installing a Lead-Bismuth Eutectic (LBE) spallation target in the SINQ facility. Efforts are coordinated under the MEGAPIE project, the main objectives of which are to design, build, operate and decommission a 1 MW spallation neutron source. The technology and experience of building and operating a high power spallation target are of general interest in the design of an Accelerator Driven System (ADS) and in this context MEGAPIE is one of the key experiments. The target cooling is one of the important aspects of the target system design that needs to be studied in detail. Calculations were performed previously using the RELAP5/Mod 3.2.2 and ATHLET codes, but in order to verify the previous code results and to provide another capability to model LBE systems, a similar study of the MEGAPIE target cooling system has been conducted with the TRAC/AAA code. In this paper a comparison is presented for the steady-state results obtained using the above codes. Analysis of transients, such as unregulated cooling of the target, loss of heat sink, the main electro-magnetic pump trip of the LBE loop and unprotected proton beam trip, were studied with TRAC/AAA and compared to those obtained earlier using RELAP5/Mod 3.2.2. This work extends the existing validation data-base of TRAC/AAA to heavy liquid metal systems and comprises the first part of the TRAC/AAA code validation study for LBE systems based on data from the MEGAPIE test facility and corresponding inter-code comparisons. (authors)

  13. Pareto front analysis of 6 and 15 MV dynamic IMRT for lung cancer using pencil beam, AAA and Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Ottosson, R O; Karlsson, A; Behrens, C F, E-mail: riolot01@heh.regionh.d [Department of Oncology (R), Division of Radiophysics (52AA), Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev (Denmark)

    2010-08-21

    The pencil beam dose calculation method is frequently used in modern radiation therapy treatment planning regardless of the fact that it is documented inaccurately for cases involving large density variations. The inaccuracies are larger for higher beam energies. As a result, low energy beams are conventionally used for lung treatments. The aim of this study was to analyze the advantages and disadvantages of dynamic IMRT treatment planning for high and low photon energy in order to assess if deviating from the conventional low energy approach could be favorable in some cases. Furthermore, the influence of motion on the dose distribution was investigated. Four non-small cell lung cancer cases were selected for this study. Inverse planning was conducted using Varian Eclipse. A total number of 31 dynamic IMRT plans, distributed amongst the four cases, were created ranging from PTV conformity weighted to normal tissue sparing weighted. All optimized treatment plans were calculated using three different calculation algorithms (PBC, AAA and MC). In order to study the influence of motion, two virtual lung phantoms were created. The idea was to mimic two different situations: one where the GTV is located centrally in the PTV and another where the GTV was close to the edge of the PTV. PBC is in poor agreement with MC and AAA for all cases and treatment plans. AAA overestimates the dose, compared to MC. This effect is more pronounced for 15 than 6 MV. AAA and MC both predict similar perturbations in dose distributions when moving the GTV to the edge of the PTV. PBC, however, predicts results contradicting those of AAA and MC. This study shows that PB-based dose calculation algorithms are clinically insufficient for patient geometries involving large density inhomogeneities. AAA is in much better agreement with MC, but even a small overestimation of the dose level by the algorithm might lead to a large part of the PTV being underdosed. It is advisable to use low energy as a

  14. Pareto front analysis of 6 and 15 MV dynamic IMRT for lung cancer using pencil beam, AAA and Monte Carlo.

    Science.gov (United States)

    Ottosson, R O; Karlsson, A; Behrens, C F

    2010-08-21

    The pencil beam dose calculation method is frequently used in modern radiation therapy treatment planning regardless of the fact that it is documented inaccurately for cases involving large density variations. The inaccuracies are larger for higher beam energies. As a result, low energy beams are conventionally used for lung treatments. The aim of this study was to analyze the advantages and disadvantages of dynamic IMRT treatment planning for high and low photon energy in order to assess if deviating from the conventional low energy approach could be favorable in some cases. Furthermore, the influence of motion on the dose distribution was investigated. Four non-small cell lung cancer cases were selected for this study. Inverse planning was conducted using Varian Eclipse. A total number of 31 dynamic IMRT plans, distributed amongst the four cases, were created ranging from PTV conformity weighted to normal tissue sparing weighted. All optimized treatment plans were calculated using three different calculation algorithms (PBC, AAA and MC). In order to study the influence of motion, two virtual lung phantoms were created. The idea was to mimic two different situations: one where the GTV is located centrally in the PTV and another where the GTV was close to the edge of the PTV. PBC is in poor agreement with MC and AAA for all cases and treatment plans. AAA overestimates the dose, compared to MC. This effect is more pronounced for 15 than 6 MV. AAA and MC both predict similar perturbations in dose distributions when moving the GTV to the edge of the PTV. PBC, however, predicts results contradicting those of AAA and MC. This study shows that PB-based dose calculation algorithms are clinically insufficient for patient geometries involving large density inhomogeneities. AAA is in much better agreement with MC, but even a small overestimation of the dose level by the algorithm might lead to a large part of the PTV being underdosed. It is advisable to use low energy as a

  15. Pareto front analysis of 6 and 15 MV dynamic IMRT for lung cancer using pencil beam, AAA and Monte Carlo

    International Nuclear Information System (INIS)

    Ottosson, R O; Karlsson, A; Behrens, C F

    2010-01-01

    The pencil beam dose calculation method is frequently used in modern radiation therapy treatment planning regardless of the fact that it is documented inaccurately for cases involving large density variations. The inaccuracies are larger for higher beam energies. As a result, low energy beams are conventionally used for lung treatments. The aim of this study was to analyze the advantages and disadvantages of dynamic IMRT treatment planning for high and low photon energy in order to assess if deviating from the conventional low energy approach could be favorable in some cases. Furthermore, the influence of motion on the dose distribution was investigated. Four non-small cell lung cancer cases were selected for this study. Inverse planning was conducted using Varian Eclipse. A total number of 31 dynamic IMRT plans, distributed amongst the four cases, were created ranging from PTV conformity weighted to normal tissue sparing weighted. All optimized treatment plans were calculated using three different calculation algorithms (PBC, AAA and MC). In order to study the influence of motion, two virtual lung phantoms were created. The idea was to mimic two different situations: one where the GTV is located centrally in the PTV and another where the GTV was close to the edge of the PTV. PBC is in poor agreement with MC and AAA for all cases and treatment plans. AAA overestimates the dose, compared to MC. This effect is more pronounced for 15 than 6 MV. AAA and MC both predict similar perturbations in dose distributions when moving the GTV to the edge of the PTV. PBC, however, predicts results contradicting those of AAA and MC. This study shows that PB-based dose calculation algorithms are clinically insufficient for patient geometries involving large density inhomogeneities. AAA is in much better agreement with MC, but even a small overestimation of the dose level by the algorithm might lead to a large part of the PTV being underdosed. It is advisable to use low energy as a

  16. Expression and genomic analysis of midasin, a novel and highly conserved AAA protein distantly related to dynein

    Directory of Open Access Journals (Sweden)

    Gibbons I R

    2002-07-01

    Full Text Available Abstract Background The largest open reading frame in the Saccharomyces genome encodes midasin (MDN1p, YLR106p, an AAA ATPase of 560 kDa that is essential for cell viability. Orthologs of midasin have been identified in the genome projects for Drosophila, Arabidopsis, and Schizosaccharomyces pombe. Results Midasin is present as a single-copy gene encoding a well-conserved protein of ~600 kDa in all eukaryotes for which data are available. In humans, the gene maps to 6q15 and encodes a predicted protein of 5596 residues (632 kDa. Sequence alignments of midasin from humans, yeast, Giardia and Encephalitozoon indicate that its domain structure comprises an N-terminal domain (35 kDa, followed by an AAA domain containing six tandem AAA protomers (~30 kDa each, a linker domain (260 kDa, an acidic domain (~70 kDa containing 35–40% aspartate and glutamate, and a carboxy-terminal M-domain (30 kDa that possesses MIDAS sequence motifs and is homologous to the I-domain of integrins. Expression of hemagglutamin-tagged midasin in yeast demonstrates a polypeptide of the anticipated size that is localized principally in the nucleus. Conclusions The highly conserved structure of midasin in eukaryotes, taken in conjunction with its nuclear localization in yeast, suggests that midasin may function as a nuclear chaperone and be involved in the assembly/disassembly of macromolecular complexes in the nucleus. The AAA domain of midasin is evolutionarily related to that of dynein, but it appears to lack a microtubule-binding site.

  17. Characteristics of photon beams from Philips SL25 linear accelerators

    International Nuclear Information System (INIS)

    Palta, J.R.; Ayyangar, K.; Daftari, I.; Suntharalingam, N.

    1990-01-01

    The Philips SL25 accelerator is a multimodality machine offering asymmetric collimator jaws and a new type of beam bending and transport system. It produces photon beams, nominally at 6 and 25 MV, and a scattered electron beam with nine selectable energies between 4 and 22 MeV. Dosimetric characteristics for the 6- and 25-MV photon beams are presented with respect to field flatness, surface and depth dose characteristics, isodose distribution, field size factors for both open and wedged fields, and narrow beam transmission data in different materials

  18. Evaluation of the polarization properties of a Philips-type prism for the construction of imaging polarimeters

    Science.gov (United States)

    Fernandez-Borda, R.; Waluschka, E.; Pellicori, S.; Martins, J. V.; Ramos-Izquierdo, L.; Cieslak, J. D.; Thompson, P.

    2009-08-01

    The design and construction of wide FOV imaging polarimeters for use in atmospheric remote sensing requires significant attention to the prevention of artificial polarization induced by the optical elements. Surface, coatings, and angles of incidence throughout the system must be carefully designed in order to minimize these artifacts because the remaining instrumental bias polarization is the main factor which drives the final polarimetric accuracy of the system. In this work, we present a detailed evaluation and analysis to explore the possibility of retrieving the initial polarization state of the light traveling through a generic system that has inherent instrumental polarization. Our case is a wide FOV lens and a splitter device. In particular, we chose as splitter device a Philips-type prism, because it is able to divide the signal in 3 independent channels that could be simultaneously analyze to retrieve the three first elements of the Stoke vector (in atmospheric applications the elliptical polarization can be neglected [1]). The Philips-type configuration is a versatile, compact and robust prism device that is typically used in three color camera systems. It has been used in some commercial polarimetric cameras which do not claim high accuracy polarization measurements [2]. With this work, we address the accuracy of our polarization inversion and measurements made with the Philips-type beam divider.

  19. A. Philip Randolph's Attempt at Equal Economic Opportunity: A Case Study

    Science.gov (United States)

    Walker, Joel

    2013-01-01

    A. Philip Randolph, the national president of the Brotherhood of Sleeping Car Porters was one of the driving forces behind the March on Washington Movement in 1941. In frustration over the federal government's lack of support for opportunities in the booming war industries and equality in the military, Randolph had begun to organize the March…

  20. Implications of Reverse Innovation for Socio-Economic Sustainability: A Case Study of Philips China

    Directory of Open Access Journals (Sweden)

    Juan Shan

    2016-06-01

    Full Text Available The idea of reverse innovation, local innovation happening in emerging markets for the global market, has gained much academic and managerial attention in recent years. The purpose of this study is to understand how reverse innovation has successfully diffused into the product and market development strategies at Philips Inc., a prominent multinational company (MNC of the modern era. Furthermore, the study presents the success achieved by these innovations at both the domestic and global levels, along with their implications regarding socio-economic sustainability in emerging markets. In order to investigate the research questions, a case study of Philips China was conducted involving three product innovations that were found to be suitable examples of reverse innovation. After the study of extant literature on the topic, drawing from research databases, newspaper articles, and company press releases, five semi-structuredinterviews were conducted with key managers and a market practitioner to gain sufficient understanding for this exploratory study. Subsequent case analysis concludes that these innovations are examples of reverse innovation representing a new paradigm change in innovation flow. This flow of innovation from emerging markets to developed markets as confirmed by Corsi’s framework could potentially disrupt developed markets as well as contribute to ensure healthy living conditions for the population living in developing countries. If so, this represents a sustainable socio-economic change in-line with the United Nations' Sustainable Development Goal (SDG of “ensuring healthy lives and promoting well-being for all at all ages.” This is relevant as Philips aspires to be a prominent private sector player in achieving the above-stated goal by defeating non-communicable disease and strengthening local healthcare systems.

  1. Gadopentate dimeglumine enhanced MR angiography (MRA) for staging AAA: a correlation with DSA and CT

    International Nuclear Information System (INIS)

    Arlart, I.P.; Gerlach, A.; Kolb, M.; Erpenbach, S.; Wuerstlin, S.

    1997-01-01

    Purpose: To evaluate a contrast-enhanced (CE) MRA sequence for staging AAA. Methods: In 24 patients (male=20, female=4, age=44-81 y) with known AAA the abdominal aorta and its branches including the iliac arteries were imaged, using a 3D GRE-FISP sequence (1.5 T, T R /T E /FA=25/6/35, slab=100-140 mm, 32 part., FOV=440-450 mm, matrix=256x256) during an i.v. infusion of 40 ml of gadopentate dimeglumine. In addition, representative axial single slices (2D breathhold FLASH-sequence: T R /T E /FA=82/5/30) were acquired following contrast application. MR-results were correlated with i.a. DSA and CT studies. Results: With CE-MRA, AAA (n=24) and iliac aneurysms (n=17) could be evaluated in all cases (sens.=100%, spec.=100%) including luminal patency and mural thrombus. 50/54 renal arteries could be identified, 4/6 accessory renal arteries (sens=66,6%, spec.=100%), 8/9 renal artery stenoses>50% (sens.=88.8%, spec.=89.3%), 1/1 renal artery occlusion and 7/8 iliac artery stenoses>50% (sens.=87.5%, spec.=97.5%) were depicted correctly. Proximal portion of sup. mes. art. could be detected and evaluated in 21/24 cases. Quantitative determination of therapeutically relevant vascular paramters using MRA was comparable to DSA and CT. (orig./AJ) [de

  2. AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

    Science.gov (United States)

    Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

    2017-09-27

    The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  3. Integrating Philips' extreme UV source in the alpha-tools

    Science.gov (United States)

    Pankert, Joseph; Apetz, Rolf; Bergmann, Klaus; Derra, Guenther; Janssen, Maurice; Jonkers, Jeroen; Klein, Jurgen; Kruecken, Thomas; List, Andreas; Loeken, Michael; Metzmacher, Christof; Neff, Willi; Probst, Sven; Prummer, Ralph; Rosier, Oliver; Seiwert, Stefan; Siemons, Guido; Vaudrevange, Dominik; Wagemann, Dirk; Weber, Achim; Zink, Peter; Zitzen, Oliver

    2005-05-01

    The paper describes recent progress in the development of the Philips's EUV source. Progress has been realized at many frontiers: Integration studies of the source into a scanner have primarily been studied on the Xe source because it has a high degree of maturity. We report on integration with a collector, associated collector lifetime and optical characteristics. Collector lifetime in excess of 1 bln shots could be demonstrated. Next, an active dose control system was developed and tested on the Xe lamp. Resulting dose stability data are less than 0.2% for an exposure window of 100 pulses. The second part of the paper reports on progress in the development of the Philips' Sn source. First, the details of the concept are described. It is based on a Laser triggered vacuum arc, which is an extension with respect to previous designs. The source is furbished with rotating electrodes that are covered with a Sn film that is constantly regenerated. Hence by the very design of the source, it is scalable to very high power levels, and moreover has fundamentally solved the notorious problem of electrode erosion. Power values of 260 W in 2p sr are reported, along with a stable, long life operation of the lamp. The paper also addresses the problem of debris generation and mitigation of the Sn-source. The problem is attacked by a combined strategy of protection of the collector by traditional means (e.g. fields, foiltraps... ), and by designing the gas atmosphere according to the principles of the well known halogen cycles in incandescent lamps. These principles have been studied in the Lighting industry for decades and rely on the excessively high vapor pressures of metal halides. Transferred to the Sn source, it allows pumping away tin residues that would otherwise irreversibly deposit on the collector.

  4. Philips Gemini TF64 PET/CT Acceptance Testing

    International Nuclear Information System (INIS)

    González Gonzalez, Joaquín J.; Calderón Marin, Carlos F.; Varela Corona, Consuelo; Machado Tejeda, Adalberto; González Correa, Héctor J.

    2016-01-01

    The Philips Gemini TF64 is the first PET/CT scanner installed in Cuba at the Institute of Oncology and Radiobiology in 2014. It is a third generation fully tridimensional whole body PET scanner with time-of-flight (TOF) technology combined with a 64-slice Brilliance CT scanner. The CT detector module contains 672x64 solid state detector, incorporating GOS scintillators, optical diodes and electronic signal channels arranged in 64 side by side arcs, with 672 detectors in each arc. There are sixteen 0.75 mm individual detector elements around the center and four 1.5 mm elements at each end, resulting in a 24 mm total detection length. The PET detector consists of 28 pixelar modules of a 23x44 array of 4x4x22 mm3 of LYSO crystals arranged in an Anger-logic detector design. The hardware coincidence-timing window for this scanner is set at 4 ns and delayed coincidence window technique is used to estimate the random coincidences in collected data. In this study the performance characteristics of PET/CT scanner were measured as part of the program tests of acceptance for clinical use.Methodology. The performance characteristics of CT scanner were evaluated by manufacturer protocol using Philips system performance phantom. Some additional geometrical tests were performed by the user. The intrinsic measurements of energy resolution as well as timing resolution, which define the TOF performance of PET scanner, were performed following the recommendations of manufacturer using 18 F. Spatial resolution, sensitivity, scatter fraction, counting rate performance, image quality and accuracy were measured according to the NEMA NU-2 2007 procedures. Additionally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA torso phantom was reconstructed with and without TOF capability. The accuracy of PET/CT image registration was tested according to the manufacturer protocol using an image alignment calibration holder with 6 point sources of 22

  5. Anonymous Communication Policies for the Internet: Results and Recommendations of the AAAS Conference.

    Science.gov (United States)

    Teich, Al; Frankel, Mark S.; Kling, Rob; Lee, Yaching

    1999-01-01

    Reports the results of a conference on the Internet and anonymous communication organized by the American Association for the Advancement of Science (AAAS). Discusses how anonymous communications can be shaped by the law, education, and public awareness, and highlights the importance of involving all affected interests in policy development.…

  6. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters.

    Science.gov (United States)

    Bufacchi, Antonella; Nardiello, Barbara; Capparella, Roberto; Begnozzi, Luisa

    2013-07-04

    Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC's ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the mean NTCPPBC

  7. Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability.

    Science.gov (United States)

    Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

    2014-12-23

    To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans. Differences in dose distribution are observed with VMAT and CRT plans recalculated with AXB particularly within soft tissue at the tumour/lung interface, where AXB has been shown to more

  8. Caracterização do grânulo de amido de bananas (Musa AAA-Nanicão e Musa AAB-Terra Characterization of starch granules from bananas Musa AAA-Nanicão and Musa AAB-Terra

    Directory of Open Access Journals (Sweden)

    M.C.J. Freitas

    2005-06-01

    Full Text Available O amido de bananas tem sido pesquisado na área de nutrição a partir da introdução do conceito de Amido Resistente. O amido de Musa AAA-Nanicão e Musa AAB-Terra foram caracterizados quanto as suas respostas fisiológicas [12]. Em continuidade, o presente trabalho estudou características físicas e morfológicas dos grânulos de amido de ambas as espécies de banana comparando-as com amido nativo de milho comercial. O amido de bananas foi extraído segundo CHIANG, CHU & CHU [3]. A morfologia dos grânulos foi realizada após tratamento enzimático in vitro a 37°C/24h com alfa-amilase pancreática. Foram efetuados os respectivos amilogramas e difractogramas de raios-X. Os grânulos de amido da Musa Tipo AAA-Nanicão apresentaram comprimento entre 30-40µm. Em Musa AAB-Terra, os grânulos, também ovais e alongados, eram um pouco menores, 20-30µm. A corrosão enzimática in vitro iniciava-se sobre a superfície anteriormente lisa e formavam estrias superficiais e apicais. A Microscopia Eletrônica de Varredura (MEV mostrou que a hidrólise in vitro por 24 horas foi pequena e ocorria sobretudo nas camadas amorfas dos grânulos de ambas as espécies. O padrão de corrosão demonstrou-se distinto daquele ocorrido no amido de milho. As suspensões de amido de bananas ao viscosímetro demonstraram forte capacidade de hidratação e menor capacidade de retrogradação em relação ao milho, sobretudo do amido de Musa Tipo AAA-Nanicão; o amido de Musa Tipo AAB-Terra apresentou maior estabilidade de pasta. Na análise de difração de raios-X, os grânulos de bananas apresentaram padrão tipo B e C para Musa Tipo AAA-Nanicão e Musa Tipo AAB-Terra, respectivamente. Conclui-se que os amidos de Musa AAA-Nanicão e Musa AAB-Terra são estruturalmente distintos, justificando as respostas fisiológicas distintas encontradas posteriormente pelos mesmos autores. As distinções das propriedades físicas e bioquímicas obtidas para os grânulos, embora

  9. Morphological State as a Predictor for Reintervention and Mortality After EVAR for AAA

    Energy Technology Data Exchange (ETDEWEB)

    Ohrlander, Tomas [Eksjoe County Hospital (Sweden); Dencker, Magnus [Malmoe University Hospital, Department of Clinical Physiology and Nuclear Medicine (Sweden); Acosta, Stefan, E-mail: stefan.acosta@telia.com [Malmoe University Hospital, Vascular Center Malmoe-Lund (Sweden)

    2012-10-15

    Purpose: This study was designed to assess aorto-iliac morphological characteristics in relation to reintervention and all-cause long-term mortality in patients undergoing standard EVAR for infrarenal AAA. Methods: Patients treated with EVAR (Zenith{sup Registered-Sign} Stentgrafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerized database where comorbidities and preoperative aneurysm morphology were entered. Reinterventions and mortality were checked until December 1, 2010. Median follow-up time was 68 months. Results: A total of 304 patients were included, of which 86% were men. Median age was 74 years. The reintervention rate was 23.4% (71/304). A greater diameter of the common iliac artery (p = 0.037; hazard ratio (HR) 1.037 [1.002-1.073]) was an independent factor for an increased number of reinterventions. The 30-day mortality rate was 3.0% (9/304). Aneurysm-related deaths due to AAA occurred in 4.9% (15/304). Five patients died due to a concomitant ruptured thoracic aortic aneurysm. The mortality until end of follow-up was 54.3% (165/304). The proportion of deaths caused by vascular diseases was 61.6%. The severity of angulation of the iliac arteries (p = 0.014; HR 1.018 [95% confidence interval (CI) 1.004-1.033]) and anemia (p = 0.044; HR 2.79 [95% CI 1.029-7.556]) remained as independent factors associated with all-cause long-term mortality. The crude reintervention-free survival rate at 1, 3, and 5 years was 84.5%, 64.8%, and 51.6%, respectively. Conclusions: The initial aorto-iliac morphological state in patients scheduled for standard EVAR for AAA seems to be strongly related to the need for reinterventions and long-term mortality.

  10. BACTERIAL CONTAMINATION CONTROL IN BANANA EXPLANTS (Musa AAA cv. CAIPIRA) CONTROLE DE BACTÉRIAS CONTAMINANTES EM EXPLANTES DE BANANEIRA (Musa AAA cv. CAIPIRA)

    OpenAIRE

    Juliana Domingues Lima; Wilson da Silva Moraes

    2007-01-01

    Esse trabalho teve por objetivo testar métodos de controle de contaminação bacteriana no processo de multiplicação in vitro de bananeira (Musa AAA cv. Caipira), utilizando-se hipoclorito de sódio (NaOCl), antibiótico rifampicina e suas combinações. Não houve oxidação excessiva dos explantes após a imersão em NaOCl ou rifampicina. O melhor tratamento para explantes recém isolados foi imersão em NaOCl a 1% (v/v), dura...

  11. Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin ligase, mysterin/RNF213

    Science.gov (United States)

    Kotani, Yuri; Morito, Daisuke; Yamazaki, Satoru; Ogino, Kazutoyo; Kawakami, Koichi; Takashima, Seiji; Hirata, Hiromi; Nagata, Kazuhiro

    2015-01-01

    Mysterin (also known as RNF213) is a huge intracellular protein with two AAA+ ATPase modules and a RING finger ubiquitin ligase domain. Mysterin was originally isolated as a significant risk factor for the cryptogenic cerebrovascular disorder moyamoya disease, and was found to be involved in physiological angiogenesis in zebrafish. However, the function and the physiological significance of mysterin in other than blood vessels remain largely unknown, although mysterin is ubiquitously expressed in animal tissues. In this study, we performed antisense-mediated suppression of a mysterin orthologue in zebrafish larvae and revealed that mysterin-deficient larvae showed significant reduction in fast myofibrils and immature projection of primary motoneurons, leading to severe motor deficits. Fast muscle-specific restoration of mysterin expression cancelled these phenotypes, and interestingly both AAA+ ATPase and ubiquitin ligase activities of mysterin were indispensable for proper fast muscle formation, demonstrating an essential role of mysterin and its enzymatic activities in the neuromuscular regulation in zebrafish. PMID:26530008

  12. Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

    Science.gov (United States)

    Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

    2015-01-01

    Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

  13. Paradise Lost and Found: Obedience, Disobedience, and Storytelling in C.S. Lewis and Philip Pullman.

    Science.gov (United States)

    Wood, Naomi

    2001-01-01

    Considers how in the fantasy series "The Chronicles of Narnia" and "His Dark Materials," by C.S. Lewis and Philip Pullman respectively, the authors use symbols and themes from "Paradise Lost." Notes that each author's narrative choice uses his view of cosmic order to persuade readers that obedience should be…

  14. PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

    Science.gov (United States)

    Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

    2015-11-01

    Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

  15. Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability

    International Nuclear Information System (INIS)

    Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

    2014-01-01

    To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy −1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans

  16. SU-E-P-16: A Feasibility Study of Using Eclipse AAA for SRS Treatement

    International Nuclear Information System (INIS)

    Lim, S; LoSasso, T

    2015-01-01

    Purpose: To commission Varian Eclipse AAA for SRS treatment and compare the accuracy with Brainlab iPlan system for clinical cases measured with radiochromic film. Methods: A 6MV AAA clinical model for a Varian TrueBeam STx is used as baseline. The focal spot and field size of the baseline model(BASE) are (1.75,0.75) and 40×40cm 2 respectively. Maximum field sizes, output factors(S t ), FWHM focal spot and secondary source sizes are systematically adjusted to obtain an optimized model(OPT) by comparing the calculated PDD’s, profiles, and output factors with measurements taken with a stereotactic diode(SD) and, cc01 and cc04 ion chambers in Blue Phantom. In-phantom dose distributions of clinical SRS fields are calculated using the OPT and the clinical Brainlab iPlan pencil-beam. Within the 90% isodose-line(ROI), the average dose difference between the calculations and radiochromic film measurements are assessed. Results: The maximum field, focal spot and secondary source sizes for the OPT are 15×15cm 2 , (0,0), and 32.3mm respectively. The OPT St input at 1.0 and 2.0cm fields are increased by 4.5% and 1.5% from BASE. The calculated output of the BASE and OPT underestimate by 16.1%–3.2% respectively at 0.5×0.5cm 2 field and 3.1%−0.02% respectively at 1.0×1.0cm 2 field. The depth doses at 10cm are within 3.5% and 0.4% of measurements for 0.5×0.5 and 1.0×1.0cm 2 . The ROI dose of OPT and iPlan are within 1.6% and 0.6% of film measurements for 3.0cm clinical fields. For 1.0cm fields, the ROI dose of OPT underestimate 0.0–2.0% and iPlan overestimates 1.7–2.9% relative to measurements. Conclusion: The small field dose calculation of Eclipse AAA algorithm can be significantly improved by carefully adjusting the input parameters. The larger deviation of the OPT for 0.5×0.5cm 2 field from measurements can be attributed to the lowest 1.0cm field size input limit of AAA. The OPT compares reasonably well with the iPlan pencil-beam and measurements

  17. SU-E-P-16: A Feasibility Study of Using Eclipse AAA for SRS Treatement

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S; LoSasso, T [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2015-06-15

    Purpose: To commission Varian Eclipse AAA for SRS treatment and compare the accuracy with Brainlab iPlan system for clinical cases measured with radiochromic film. Methods: A 6MV AAA clinical model for a Varian TrueBeam STx is used as baseline. The focal spot and field size of the baseline model(BASE) are (1.75,0.75) and 40×40cm{sup 2} respectively. Maximum field sizes, output factors(S{sub t}), FWHM focal spot and secondary source sizes are systematically adjusted to obtain an optimized model(OPT) by comparing the calculated PDD’s, profiles, and output factors with measurements taken with a stereotactic diode(SD) and, cc01 and cc04 ion chambers in Blue Phantom. In-phantom dose distributions of clinical SRS fields are calculated using the OPT and the clinical Brainlab iPlan pencil-beam. Within the 90% isodose-line(ROI), the average dose difference between the calculations and radiochromic film measurements are assessed. Results: The maximum field, focal spot and secondary source sizes for the OPT are 15×15cm{sup 2}, (0,0), and 32.3mm respectively. The OPT St input at 1.0 and 2.0cm fields are increased by 4.5% and 1.5% from BASE. The calculated output of the BASE and OPT underestimate by 16.1%–3.2% respectively at 0.5×0.5cm{sup 2} field and 3.1%−0.02% respectively at 1.0×1.0cm{sup 2} field. The depth doses at 10cm are within 3.5% and 0.4% of measurements for 0.5×0.5 and 1.0×1.0cm{sup 2}. The ROI dose of OPT and iPlan are within 1.6% and 0.6% of film measurements for 3.0cm clinical fields. For 1.0cm fields, the ROI dose of OPT underestimate 0.0–2.0% and iPlan overestimates 1.7–2.9% relative to measurements. Conclusion: The small field dose calculation of Eclipse AAA algorithm can be significantly improved by carefully adjusting the input parameters. The larger deviation of the OPT for 0.5×0.5cm{sup 2} field from measurements can be attributed to the lowest 1.0cm field size input limit of AAA. The OPT compares reasonably well with the iPlan pencil

  18. When Harry met Zuckerman: self-reflexivity and metafiction in Philip Roth and Woody Allen When Harry met Zuckerman:self-reflexivity and metafiction in Philip Roth and Woody Allen

    Directory of Open Access Journals (Sweden)

    Thomás Creus

    2008-04-01

    Full Text Available The objective of this essay is to compare the works of novelist Philip Roth and film-maker Woody Allen in what regards their treatment of the highly complex theme of the interrelations between fiction and reality. A comparative analysis of selected Roth’s novels and Allen’s films evinces their recurrent preoccupation with the creation of art and its implications, be it through the choice of writers or artists as main characters, be it through plots that mix real facts with invented ones and imaginary characters with real ones, be it through the use of autobiographical elements in a fictional discourse—all metafictional devices that call attention to the artist’s own process of creation. The objective of this essay is to compare the works of novelist Philip Roth and film-maker Woody Allen in what regards their treatment of the highly complex theme of the interrelations between fiction and reality. A comparative analysis of selected Roth’s novels and Allen’s films evinces their recurrent preoccupation with the creation of art and its implications, be it through the choice of writers or artists as main characters, be it through plots that mix real facts with invented ones and imaginary characters with real ones, be it through the use of autobiographical elements in a fictional discourse—all metafictional devices that call attention to the artist’s own process of creation.

  19. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    Science.gov (United States)

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  20. Managing between science and industrie: An historical analysis of the Philips Research and Development Department's management

    NARCIS (Netherlands)

    Boersma, F.K.

    2007-01-01

    Purpose This paper seeks to deal with the history of Research and Development (R&D) management. It takes the history of the R&D Department of the Royal Philips Electronics of The Netherlands as an example to unravel the dynamics behind industrial R&D management. Designomethodologyoapproach This

  1. 76 FR 71048 - Sixth Annual Philip S. Chen, Jr. Distinguished Lecture on Innovation and Technology Transfer

    Science.gov (United States)

    2011-11-16

    ... present ``Treatment of Cancer with Recombinant Immunotoxins: From Technology Transfer to the Patient.'' Dr. Pastan is an NIH Distinguished Investigator and Chief, Laboratory of Molecular Biology, National Cancer Institute Center for Cancer Research. This annual series honors Dr. Philip S. Chen, Jr. for his almost 50...

  2. The Philip Morris Genome Project: a guide to tracking alliances of the world´s largest cigarette company

    Directory of Open Access Journals (Sweden)

    Alan Blum

    2018-03-01

    Full Text Available Background Beginning in the 1980s, tobacco control efforts shifted from school-based and clinic-based education about the dangers of smoking to direct confrontation of the tobacco industry. But the industry also evolved by developing innovative promotional campaigns, adopting new corporate identities, and forging alliances with other industries and charitable organizations. Methods To document the extent of the commercial, civic, political, academic, military,and cultural ties cultivated by the world´s largest cigarette manufacturer, Philip Morris, a continuous, 35-year ethnographic analysis was conducted, involving daily monitoring of the global business press; monthly review of tobacco industry trade publications; scrutiny of annual company reports; and attendance at 20 shareholders´ meetings, four international tobacco industry trade expositions, and over 200 sports, arts, and ethnic minority events sponsored by the company. Results 48 Philip Morris manufacturing facilities in 32 countries produce more than 800 billion cigarettes a year for 180 markets..A pioneer in sponsoring popular programs on the new medium of television in the 1950s; the company circumvented the 1971 ban on TV cigarette advertising by creating sporting events that were internationally televised. By acquiring beer and food companies In the 1980s, Philip Morris retained influence over the mass media covetous of advertising revenue. In 2002 the company changed its name to Altria to diminish the tobacco stigma. It makes the world´s top cigarette brand, Marlboro, and holds 28% of the global market excluding China. The company has forged an extensive network of alliances with agricultural, marketing, chemical, pharmaceutical, financial, packaging, entertainment, shipping, and technology companies, as well as ties to hundreds of museums, arts organizations, universities, libraries, and charities combating problems such as domestic violence, hunger, pollution, illiteracy, and

  3. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1.

    Science.gov (United States)

    Esser, Karlheinz; Tursun, Baris; Ingenhoven, Martin; Michaelis, Georg; Pratje, Elke

    2002-11-08

    The yeast protein cytochrome c peroxidase (Ccp1) is nuclearly encoded and imported into the mitochondrial intermembrane space, where it is involved in degradation of reactive oxygen species. It is known, that Ccp1 is synthesised as a precursor with a N-terminal pre-sequence, that is proteolytically removed during transport of the protein. Here we present evidence for a new processing pathway, involving novel signal peptidase activities. The mAAA protease subunits Yta10 (Afg3) and Yta12 (Rca1) were identified both to be essential for the first processing step. In addition, the Pcp1 (Ygr101w) gene product was found to be required for the second processing step, yielding the mature Ccp1 protein. The newly identified Pcp1 protein belongs to the rhomboid-GlpG superfamily of putative intramembrane peptidases. Inactivation of the protease motifs in mAAA and Pcp1 blocks the respective steps of proteolysis. A model of coupled Ccp1 transport and N-terminal processing by the mAAA complex and Pcp1 is discussed. Similar processing mechanisms may exist, because the mAAA subunits and the newly identified Pcp1 protein belong to ubiquitous protein families.

  4. Detecting endoleaks after endovascular AAA repair with a minimally invasive, implantable, telemetric pressure sensor: an in vitro study

    International Nuclear Information System (INIS)

    Springer, Fabian; Pfeffer, Joachim-Georg; Schmitz-Rode, Thomas; Schlierf, Roland; Schnakenberg, Uwe; Mahnken, Andreas H.

    2007-01-01

    A feasibility study on a completely digital telemetric pressure sensor (TPS) to detect endoleaks was performed in an in vitro model of an abdominal aortic aneurysm (AAA). An endovascular-stented AAA silicone model with different types (I-III) and sizes (3-11 French) of endoleaks was created and pulsatile pressure was applied with physiological flow and pressure rates [mean intraaortic pressure (IAP): 95-130 mmHg] and different degrees of thrombosis of the aneurysm sac. Aneurysm sac pressure (ASP) was measured with the TPS and with wired pressure sensors (WPS) as a reference. Statistical analysis included paired t-test, Pearson's correlation analysis and Bland-Altman plots. After opening an endoleak, the mean ASP increased significantly (P < 0.0001) from 15 to almost 95% of the mean IAP depending on endoleak type and size. ASP could be measured accurately with the TPS and the WPS. The telemetric and wired ASP increase showed a high Pearson's correlation coefficient (r) for a non-thrombosed (r 0.97) and a thrombosed (r = 0.96) aneurysm sac. In an in vitro silicone model, the newly designed telemetric pressure sensor was able to detect the occurrence of an endoleak in a non-invasive way and might be a valuable device for follow-up of endovascular AAA repair. (orig.)

  5. The mechanical role of thrombus on the growth rate of an abdominal aortic aneurysm (AAA)

    NARCIS (Netherlands)

    Speelman, L.; Schurink, G.W.H.; Bosboom, E.M.H.; Buth, J.; Breeuwer, M.; Vosse, van de F.N.; Jacobs, M.J.H.M.

    2010-01-01

    Objectives: In the decision for surgical repair of abdominal aortic aneurysms (AAAs), the maximum diameter is the main factor. Several studies have concluded that the diameter may not be reliable as rupture risk criterion for the individual patient and wall stress was found to have a higher

  6. SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

    International Nuclear Information System (INIS)

    Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S

    2016-01-01

    Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V_2_0 and V_5 to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm"3. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V_2_0 (+3.1%) and V_5 (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm

  7. SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S [Montefiore Medical Center, Bronx, NY (United States)

    2016-06-15

    Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates

  8. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1

    NARCIS (Netherlands)

    Prattes, M.; Loibl, M.; Zisser, G.; Luschnig, D.; Kappel, L.; Rossler, I.; Grassegger, M.; Hromic, A.; Krieger, E.; Gruber, K.; Pertschy, B.; Bergler, H.

    2017-01-01

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP

  9. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.

    Science.gov (United States)

    Ye, Qiaozhen; Rosenberg, Scott C; Moeller, Arne; Speir, Jeffrey A; Su, Tiffany Y; Corbett, Kevin D

    2015-04-28

    The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

  10. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Qiaozhen [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Rosenberg, Scott C. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Moeller, Arne [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Speir, Jeffrey A. [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Su, Tiffany Y. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Corbett, Kevin D. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States

    2015-04-28

    The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

  11. Boron toxicity in banana (Musa AAA) plantations of Costa Rica

    International Nuclear Information System (INIS)

    Vargas, Alfonso; Serrano, Edgardo; Arias, Fulvio; Arias M, Oscar

    2007-01-01

    A marginal, irregular and continuous necrosis was observed in the leaves of in banana plants (Musa AAA, cvs. Grande Naine and Valery), This necrosis was developed from an irregular chlorotic area, from the edge towards the internal part of the leaf blade. The central portion of the leaf kept the original green color. Soil and foliar analyses showed that symptoms were caused by high boron concentrations, probably due to excessive soil or foliage applications of the nutriment, or to the effect of very frequent applications of boron during fertigation, combined with a decrease of calcium in the leaf. (author) [es

  12. Philip Roth's The human stain and the destruction of the American dream

    Directory of Open Access Journals (Sweden)

    Miha Vrčko

    2006-12-01

    Full Text Available The paper dissects the notion of the American Dream in Philip Roth's The Human Stain. It looks at how individual tenets of the Dream are carved into the protagonist Coleman Silk, a black man who goes through life pretending to be white. The analysis shows how these same principles are questioned through various incidents in Silk's life and ultimately by his violent death. The result of Roth's scrutinizing is that, as all the underminings come together, the whole concept of the American Dream is symbolically crushed.

  13. Nashemu zdravoohraneniju trebujetsja skoraja pomoshtsh / interv. Boris Tuch

    Index Scriptorium Estoniae

    2002-01-01

    Ajalehe toimetuses korraldatud ümarlaud, millest võtsid osa N. Elshtein, M. Grintshak, A. Haug ja P. Mardna arutas olukorda Eesti ravimiturul; haigekassast, tervishoiu finantseerimisest, perearstindusest. Parlamendisaadik (A. Haug)

  14. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

    Science.gov (United States)

    Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

    2018-04-12

    Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright

  15. Soil physical properties influencing the fitting parameters in Philip and Kostiakov infiltration models

    International Nuclear Information System (INIS)

    Mbagwu, J.S.C.

    1994-05-01

    Among the many models developed for monitoring the infiltration process those of Philip and Kostiakov have been studied in detail because of their simplicity and the ease of estimating their fitting parameters. The important soil physical factors influencing the fitting parameters in these infiltration models are reported in this study. The results of the study show that the single most important soil property affecting the fitting parameters in these models is the effective porosity. 36 refs, 2 figs, 5 tabs

  16. Management of pediatric radiation dose using Philips fluoroscopy systems DoseWise: perfect image, perfect sense

    International Nuclear Information System (INIS)

    Stueve, Dick

    2006-01-01

    Although image quality (IQ) is the ultimate goal for accurate diagnosis and treatment, minimizing radiation dose is equally important. This is especially true when pediatric patients are examined, because their sensitivity to radiation-induced cancer is two to three times greater than that of adults. DoseWise is an ALARA-based philosophy within Philips Medical Systems that is active at every level of product design. It encompasses a set of techniques, programs and practices that ensures optimal IQ while protecting people in the X-ray environments. DoseWise methods include management of the X-ray beam, less radiation-on time and more dose information for the operator. Smart beam management provides automatic customization of the X-ray beam spectrum, shape, and pulse frequency. The Philips-patented grid-controlled fluoroscopy (GCF) provides grid switching of the X-ray beam in the X-ray tube instead of the traditional generator switching method. In the examination of pediatric patients, DoseWise technology has been scientifically documented to reduce radiation dose to <10% of the dose of traditional continuous fluoroscopy systems. The result is improved IQ at a significantly lower effective dose, which contributes to the safety of patients and staff. (orig.)

  17. Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

    Science.gov (United States)

    Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca

    2016-10-01

    Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the

  18. Accuracy of Acuros XB and AAA dose calculation for small fields with reference to RapidArc stereotactic treatments

    International Nuclear Information System (INIS)

    Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Cozzi, Luca

    2011-01-01

    Purpose: To assess the accuracy against measurements of two photon dose calculation algorithms (Acuros XB and the Anisotropic Analytical algorithm AAA) for small fields usable in stereotactic treatments with particular focus on RapidArc. Methods: Acuros XB and AAA were configured for stereotactic use. Baseline accuracy was assessed on small jaw-collimated open fields for different values for the spot sizes parameter in the beam data: 0.0, 0.5, 1, and 2 mm. Data were calculated with a grid of 1 x 1 mm 2 . Investigated fields were: 3 x 3, 2 x 2, 1 x 1, and 0.8 x 0.8 cm 2 with a 6 MV photon beam generated from a Clinac2100iX (Varian, Palo Alto, CA). Profiles, PDD, and output factors were measured in water with a PTW diamond detector (detector size: 4 mm 2 , thickness 0.4 mm) and compared to calculations. Four RapidArc test plans were optimized, calculated and delivered with jaw settings J3 x 3, J2 x 2, and J1 x 1 cm 2 , the last was optimized twice to generate high (H) and low (L) modulation patterns. Each plan consisted of one partial arc (gantry 110 deg. to 250 deg.), and collimator 45 deg. Dose to isocenter was measured in a PTW Octavius phantom and compared to calculations. 2D measurements were performed by means of portal dosimetry with the GLAaS method developed at authors' institute. Analysis was performed with gamma pass-fail test with 3% dose difference and 2 mm distance to agreement thresholds. Results: Open square fields: penumbrae from open field profiles were in good agreement with diamond measurements for 1 mm spot size setting for Acuros XB, and between 0.5 and 1 mm for AAA. Maximum MU difference between calculations and measurements was 1.7% for Acuros XB (0.2% for fields greater than 1 x 1 cm 2 ) with 0.5 or 1 mm spot size. Agreement for AAA was within 0.7% (2.8%) for 0.5 (1 mm) spot size. RapidArc plans: doses were evaluated in a 4 mm diameter structure at isocenter and computed values differed from measurements by 0.0, -0.2, 5.5, and -3.4% for

  19. Abo1, a conserved bromodomain AAA?ATPase, maintains global nucleosome occupancy and organisation

    OpenAIRE

    Gal, Csenge; Murton, Heather E; Subramanian, Lakxmi; Whale, Alex J; Moore, Karen M; Paszkiewicz, Konrad; Codlin, Sandra; B?hler, J?rg; Creamer, Kevin M; Partridge, Janet F; Allshire, Robin C; Kent, Nicholas A; Whitehall, Simon K

    2015-01-01

    Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1+ experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II. Abo1 is rec...

  20. A group find of the bronze coins struck under Philip II and Alexander III from Svoboda near Plovdiv (Bulgaria)

    Czech Academy of Sciences Publication Activity Database

    Militký, Jiří

    2013-01-01

    Roč. 27, č. 2 (2013), s. 147-160 ISSN 0546-9414 R&D Projects: GA ČR GA13-24707S Institutional support: RVO:67985912 Keywords : Macedonia * Bulgaria * Philip II * hoard Subject RIV: AC - Archeology, Anthropology, Ethnology

  1. Three Experts on Quality Management: Philip B. Crosby, W. Edwards Deming, Joseph M. Juran

    Science.gov (United States)

    1992-07-01

    Department of the Navy Office of the Under Secretary of the Navy Total Quality Leadership Omce THREE EXPERTS ON QUALITY MANAGEMENT : PHILIP B. CROSBY W...research, as the "price of nonconformance." To aid managers in statistical theory , statistical thinking, and the application tracking the cost of doing...Quality Management emphasizes that the process must become a way of life in Theory of Systems. "A system is a series of the organization. Continuance is

  2. Student-Athlete Perceptions of a Summer Pre-Enrollment Experience at an NCAA Division I-AAA Institution

    Science.gov (United States)

    Dalgety, Michael Franklin

    2012-01-01

    The purpose of this exploratory qualitative study was to examine student-athlete perceptions of the role of summer pre-enrollment in their adjustment and transition to college. The study focused on student-athletes who received athletically-related financial aid at a National Collegiate Athletic Association (NCAA) Division I-AAA institution. The…

  3. Study on Computerized Treatment Plan of Field-in-Field Intensity Modulated Radiation Therapy and Conventional Radiation Therapy according to PBC Algorithm and AAA on Breast Cancer Tangential Beam

    International Nuclear Information System (INIS)

    Yeom, Mi Suk; Bae, Seong Soo; Kim, Dae Sup; Back, Geum Mun

    2012-01-01

    Anisotropic Analytical Algorithm (AAA) provides more accurate dose calculation regarding impact on scatter and tissue inhomogeneity in comparison to Pencil Beam Convolution (PBC) algorithm. This study tries to analyze the difference of dose distribution according to PBC algorithm and dose calculation algorithm of AAA on breast cancer tangential plan. Computerized medical care plan using Eclipse treatment planning system (version 8.9, VARIAN, USA) has been established for the 10 breast cancer patients using 6 MV energy of Linac (CL-6EX, VARIAN, USA). After treatment plan of Conventional Radiation Therapy plan (Conventional plan) and Field-in-Field Intensity Modulated Radiation Therapy plan (FiF plan) using PBC algorithm has been established, MU has been fixed, implemented dose calculation after changing it to AAA, and compared and analyzed treatment plan using Dose Volume Histogram (DVH). Firstly, as a result of evaluating PBC algorithm of Conventional plan and the difference according to AAA, the average difference of CI value on target volume has been highly estimated by 0.295 on PBC algorithm and as a result of evaluating dose of lung, V 47 Gy and has been highly evaluated by 5.83% and 4.04% each, Mean dose, V 20 , V 5 , V 3 Gy has been highly evaluated 0.6%, 0.29%, 6.35%, 10.23% each on AAA. Secondly, in case of FiF plan, the average difference of CI value on target volume has been highly evaluated on PBC algorithm by 0.165, and dose on ipsilateral lung, V 47 , V 45 Gy, Mean dose has been highly evaluated 6.17%, 3.80%, 0.15% each on PBC algorithm, V 20 , V 5 , V 3 Gy has been highly evaluated 0.14%, 4.07%, 4.35% each on AAA. When calculating with AAA on breast cancer tangential plan, compared to PBC algorithm, Conformity on target volume of Conventional plan, FiF plan has been less evaluated by 0.295, 0.165 each. For the reason that dose of high dose region of ipsilateral lung has been showed little amount, and dose of low dose region has been showed much amount

  4. Bedrijfsmatige bemiddeling. Philips en Unilever en de marketing van radio's, televisies en snacks in Nederland in de twintigste eeuw

    NARCIS (Netherlands)

    de Wit, Onno; Albert de la Bruheze, Adri A.

    2002-01-01

    Mediation practices show a wide variety. This article focuses upon mediation processes initiated by corporations. Within the context of two multinational companies, Philips and Unilever, the development, introduction and diffusion of radio and television sets and snacks in the Netherlands is

  5. Turning free speech into corporate speech: Philip Morris' efforts to influence U.S. and European journalists regarding the U.S. EPA report on secondhand smoke.

    Science.gov (United States)

    Muggli, Monique E; Hurt, Richard D; Becker, Lee B

    2004-09-01

    Previously secret internal tobacco company documents show that the tobacco industry launched an extensive multifaceted effort to influence the scientific debate about the harmful effects of secondhand smoke. Integral to the industry's campaign was an effort to derail the Environmental Protection Agency's (EPA) risk assessment on environmental tobacco smoke (ETS) by recruiting a network of journalists to generate news articles supporting the industry's position and pushing its public relations messages regarding the ETS issue. Searches of previously secret internal tobacco industry records were conducted online and at the Minnesota Tobacco Document Depository. In addition, searches on the World Wide Web were conducted for each National Journalism Center alumnus. Lexis-Nexis was used to locate news stories written by the journalists cited in this paper. Philip Morris turned to its public relations firm Burson Marsteller to "build considerable reasonable doubt em leader particularly among consumers" about the "scientific weaknesses" of the EPA report. A Washington, DC, media and political consultant Richard Hines was a key player in carrying out Burson Marsteller's media recommendations of "EPA bashing" for Philip Morris. In March 1993, Philip Morris' vice president of corporate affairs policy and administration reported to Steve Parrish, vice president and general counsel of Philip Morris, that their consultant was "responsible for a number of articles that have appeared in em leader major news publications regarding EPA and ETS." In addition to placing favorable stories in the press through its consultant, Philip Morris sought to expand its journalist network by financially supporting a U.S. school of journalism; the National Journalism Center (NJC). Philip Morris gleaned "about 15 years worth of journalists at print and visual media throughout the country em leader to get across [its] side of the story" resulting in "numerous pieces consistent with our point of

  6. Accuracy of Acuros XB and AAA dose calculation for small fields with reference to RapidArc stereotactic treatments

    Energy Technology Data Exchange (ETDEWEB)

    Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Cozzi, Luca [Oncology Institute of Southern Switzerland, Medical Physics Unit, CH-6500 Bellinzona (Switzerland)

    2011-11-15

    Purpose: To assess the accuracy against measurements of two photon dose calculation algorithms (Acuros XB and the Anisotropic Analytical algorithm AAA) for small fields usable in stereotactic treatments with particular focus on RapidArc. Methods: Acuros XB and AAA were configured for stereotactic use. Baseline accuracy was assessed on small jaw-collimated open fields for different values for the spot sizes parameter in the beam data: 0.0, 0.5, 1, and 2 mm. Data were calculated with a grid of 1 x 1 mm{sup 2}. Investigated fields were: 3 x 3, 2 x 2, 1 x 1, and 0.8 x 0.8 cm{sup 2} with a 6 MV photon beam generated from a Clinac2100iX (Varian, Palo Alto, CA). Profiles, PDD, and output factors were measured in water with a PTW diamond detector (detector size: 4 mm{sup 2}, thickness 0.4 mm) and compared to calculations. Four RapidArc test plans were optimized, calculated and delivered with jaw settings J3 x 3, J2 x 2, and J1 x 1 cm{sup 2}, the last was optimized twice to generate high (H) and low (L) modulation patterns. Each plan consisted of one partial arc (gantry 110 deg. to 250 deg.), and collimator 45 deg. Dose to isocenter was measured in a PTW Octavius phantom and compared to calculations. 2D measurements were performed by means of portal dosimetry with the GLAaS method developed at authors' institute. Analysis was performed with gamma pass-fail test with 3% dose difference and 2 mm distance to agreement thresholds. Results: Open square fields: penumbrae from open field profiles were in good agreement with diamond measurements for 1 mm spot size setting for Acuros XB, and between 0.5 and 1 mm for AAA. Maximum MU difference between calculations and measurements was 1.7% for Acuros XB (0.2% for fields greater than 1 x 1 cm{sup 2}) with 0.5 or 1 mm spot size. Agreement for AAA was within 0.7% (2.8%) for 0.5 (1 mm) spot size. RapidArc plans: doses were evaluated in a 4 mm diameter structure at isocenter and computed values differed from measurements by 0.0, -0

  7. Experimental verification of the Acuros XB and AAA dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma.

    Science.gov (United States)

    Kan, Monica W K; Leung, Lucullus H T; So, Ronald W K; Yu, Peter K N

    2013-03-01

    To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (AAA) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc(®) (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic(®) EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by AAA and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB_Dm) and dose-to-water (AXB_Dw) options. Furthermore, target dose differences between AAA and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the dose close to unit density water

  8. Experimental verification of the Acuros XB and AAA dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma

    International Nuclear Information System (INIS)

    Kan, Monica W. K.; Leung, Lucullus H. T.; So, Ronald W. K.; Yu, Peter K. N.

    2013-01-01

    Purpose: To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (AAA) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc ® (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). Methods: Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic ® EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by AAA and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB Dm ) and dose-to-water (AXB Dw ) options. Furthermore, target dose differences between AAA and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. Results: For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for AAA, AXB Dm , and AXB Dw , respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for AAA, AXB Dm , and AXB Dw , respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the

  9. Philip Finkelpearl. Court and Country in the Plays of Fletcher and Beaumont Princeton: Princeton UP, 1990 Philip Finkelpearl. Court and Country in the Plays of Fletcher and Beaumont Princeton: Princeton UP, 1990

    Directory of Open Access Journals (Sweden)

    Craig Bernthal

    2008-04-01

    Full Text Available Este livro apresenta as mais recentes e talvez definitivo sobre uma parcela Philip Finkelpearl argumento foi fazendo desde 1971: que as peças de Beaumont e Flecher "não são sinais de Jacobean a decadência do teatro ", mas sim "tem que comentar as decadência da idade ". Finkelpearl produto lucidamente em uma forma empírica para provar seu ponto, apresentando-se como muitos "Teimosa factos", como ele pode mestre em apoio do seu argumento, que analisa: "os colaboradores família origens, o seu posicionamento social, seus amigos ligações, as influências das suas peças e, acima de todas as provas dos jogos propriamente ditos. Este livro apresenta as mais recentes e talvez definitivo sobre uma parcela Philip Finkelpearl argumento foi fazendo desde 1971: que as peças de Beaumont e Flecher "não são sinais de Jacobean a decadência do teatro ", mas sim "tem que comentar as decadência da idade ". Finkelpearl produto lucidamente em uma forma empírica para provar seu ponto, apresentando-se como muitos "Teimosa factos", como ele pode mestre em apoio do seu argumento, que analisa: "os colaboradores família origens, o seu posicionamento social, seus amigos ligações, as influências das suas peças e, acima de todas as provas dos jogos propriamente ditos.

  10. SU-F-T-441: Dose Calculation Accuracy in CT Images Reconstructed with Artifact Reduction Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C; Chan, S; Lee, F; Ngan, R [Queen Elizabeth Hospital (Hong Kong); Lee, V [University of Hong Kong, Hong Kong, HK (Hong Kong)

    2016-06-15

    Purpose: Accuracy of radiotherapy dose calculation in patients with surgical implants is complicated by two factors. First is the accuracy of CT number, second is the dose calculation accuracy. We compared measured dose with dose calculated on CT images reconstructed with FBP and an artifact reduction algorithm (OMAR, Philips) for a phantom with high density inserts. Dose calculation were done with Varian AAA and AcurosXB. Methods: A phantom was constructed with solid water in which 2 titanium or stainless steel rods could be inserted. The phantom was scanned with the Philips Brillance Big Bore CT. Image reconstruction was done with FBP and OMAR. Two 6 MV single field photon plans were constructed for each phantom. Radiochromic films were placed at different locations to measure the dose deposited. One plan has normal incidence on the titanium/steel rods. In the second plan, the beam is at almost glancing incidence on the metal rods. Measurements were then compared with dose calculated with AAA and AcurosXB. Results: The use of OMAR images slightly improved the dose calculation accuracy. The agreement between measured and calculated dose was best with AXB and image reconstructed with OMAR. Dose calculated on titanium phantom has better agreement with measurement. Large discrepancies were seen at points directly above and below the high density inserts. Both AAA and AXB underestimated the dose directly above the metal surface, while overestimated the dose below the metal surface. Doses measured downstream of metal were all within 3% of calculated values. Conclusion: When doing treatment planning for patients with metal implants, care must be taken to acquire correct CT images to improve dose calculation accuracy. Moreover, great discrepancies in measured and calculated dose were observed at metal/tissue interface. Care must be taken in estimating the dose in critical structures that come into contact with metals.

  11. An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.

    Science.gov (United States)

    Worden, Evan J; Dong, Ken C; Martin, Andreas

    2017-09-07

    Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination. Ubiquitin binding induces a conformational switch of Rpn11's Insert-1 loop from an inactive closed state to an active β hairpin. This switch is rate-limiting for deubiquitination and strongly accelerated by mechanical substrate translocation into the AAA+ motor. Deubiquitination by Rpn11 and ubiquitin unfolding by the ATPases are in direct competition. The AAA+ motor-driven acceleration of Rpn11 is therefore important to ensure that poly-ubiquitin chains are removed only from committed substrates and fast enough to prevent their co-degradation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System for endovascular repair.

    Science.gov (United States)

    Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni

    2017-10-01

    This paper reports the 4-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® AAA Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was AAA-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® AAA Stent

  13. Absorptive capacity in solid-state technology and international knowledge transfer : the case of Philips comparative technology transfer and society

    NARCIS (Netherlands)

    Davids, M.; Verbong, G.P.J.

    2007-01-01

    After World War II, the market for vacuum tubes was threatened by the development, first, of transistors and, later, integrated circuits. It was essential for European electronic companies, including the Dutch company Philips Electronics, to adopt American technology to gain a position in the

  14. How Philip Morris unlocked the Japanese cigarette market: lessons for global tobacco control.

    Science.gov (United States)

    Lambert, A; Sargent, J D; Glantz, S A; Ling, P M

    2004-12-01

    The Framework Convention on Tobacco Control includes tobacco advertising restrictions that are strongly opposed by the tobacco industry. Marketing strategies used by transnational tobacco companies to open the Japanese market in the absence of such restrictions are described. Analysis of internal company documents. Between 1982 and 1987 transnational tobacco companies influenced the Japanese government through the US Trade Representative to open distribution networks and eliminate advertising restrictions. US cigarette exports to Japan increased 10-fold between 1985 and 1996. Television advertising was central to opening the market by projecting a popular image (despite a small actual market share) to attract existing smokers, combined with hero-centred advertisements to attract new smokers. Philip Morris's campaigns featured Hollywood movie personalities popular with young men, including James Coburn, Pierce Brosnan, Roger Moore, and Charlie Sheen. Event sponsorships allowed television access despite restrictions. When reinstatement of television restrictions was threatened in the late 1980s, Philip Morris more than doubled its television advertising budget and increased sponsorship of televised events. By adopting voluntary advertising standards, transnational companies delayed a television advertising ban for over a decade. Television image advertising was important to establish a market, and it has been enhanced using Hollywood personalities. Television advertising bans are essential measures to prevent industry penetration of new markets, and are less effective without concurrent limits on sponsorship and promotion. Comprehensive advertising restrictions, as included in the Framework Convention for Tobacco Control, are vital for countries where transnational tobacco companies have yet to penetrate the market.

  15. Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with AAA and Their Relationship to Clinical Outcomes after Endovascular Repair.

    Science.gov (United States)

    Tenorio, Emanuel Junio Ramos; Braga, Andre Felipe Farias; Tirapelli, Daniela Pretti Da Cunha; Ribeiro, Mauricio Serra; Piccinato, Carlos Eli; Joviliano, Edwaldo Edner

    2018-03-05

    The purpose of this study was to quantify and evaluate the expression response of miRNA-191 and miRNA-455-3p endovascular repair of abdominal aortic aneurysm (AAA) based in whole blood samples. This report describes a prospective study of a single center of 30 patients with AAA who underwent endovascular repair. Blood samples were collected preoperatively and 6 months postoperatively. The differential expression of the miRNAs was performed by the real-time polymerase chain reaction method, after extraction of the RNA from the blood samples at the 2 moments. In addition, bioinformatic tools were used to determine pathophysiological pathways related to AAA. The miR-191 and miR-455-3p were overexpressed preoperatively. After 6 months postoperatively, miR-191 (median 0.98, IQR 0.5-2.1, P AAA showed no significant differences in the expression of miR-191 and miR-455-3p. Exclusion of the aneurysmal sac after endovascular treatment induces a decrease in the expression of the studied miRNAs in whole blood samples, which suggests a possible use of them as biomarkers of therapeutic success. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report

    Directory of Open Access Journals (Sweden)

    Stuart Caroline

    2004-06-01

    Full Text Available Abstract Background Triple-A syndrome (Allgrove syndrome is an autosomal recessive disorder characterized by adrenal insufficiency, alacrima, achalasia, and – occasionally – autonomic instability. Mutations have been found in the AAAS gene on 12q13. Case presentation We present the case of a 12 year-old boy with classic systemic features of triple-A syndrome and several prominent ophthalmic features, including: accommodative spasm, dry eye, superficial punctate keratopathy, and pupillary hypersensitivity to dilute pilocarpine. MRI showed small lacrimal glands bilaterally. DNA sequencing of PCR-amplified fragments from the 16 exons of the AAAS gene revealed compound heterozygosity for a new, out-of-frame 5-bp deletion in exon 15, c1368-1372delGCTCA, and a previously-described nonsense mutation in exon 9, c938C>T, R286X. Conclusions In addition to known ophthalmic manifestations, triple-A syndrome can present with accommodative dysregulation and ocular signs of autonomic dysfunction.

  17. Chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) with massive vertebral bone erosion: computed tomography (CT), magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings.

    Science.gov (United States)

    Nakano, Sachiko; Okauchi, Kenzo; Tsushima, Yoshito

    2014-02-01

    A 62-year-old male presented with sudden onset of low back and right leg pain. Contrast-enhanced computed tomography demonstrated an abdominal aortic aneurysm (AAA), along with a large mass lesion causing vertebral body erosion. Magnetic resonance imaging (MRI) suggested that the mass lesion consisted of a chronic hematoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated increased uptake around the mass lesion, but not around the AAA. Surgical intervention was performed, and the subsequent histological diagnosis was chronic contained rupture of AAA. The mass lesion consisted of chronic hematoma and necrosis with inflammatory cell infiltration and hemosiderin deposition. This condition mimics some neoplastic diseases, but MRI and FDG-PET findings may help establish the correct diagnosis.

  18. Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

    Energy Technology Data Exchange (ETDEWEB)

    Zeymer, Cathleen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

    2014-02-01

    High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg{sup 2+} ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis.

  19. Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

    International Nuclear Information System (INIS)

    Zeymer, Cathleen; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen

    2014-01-01

    High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg 2+ ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis

  20. "What Is Our Story?" Philip Morris's Changing Corporate Narrative.

    Science.gov (United States)

    McDaniel, Patricia A; Malone, Ruth E

    2015-10-01

    We sought to learn how employees reacted to changes in the corporate narrative of Philip Morris Companies (PMC) in the late 1990s and early 2000s. We analyzed archival internal tobacco industry documents about PMC's creation of a new corporate story. In response to litigation and public opprobrium, PMC replaced its market success-oriented corporate narrative with a new one centered on responsibility. Although management sought to downplay inconsistencies between the old and new narratives, some employees reportedly had difficulty reconciling them, concerned that the responsibility focus might affect company profitability. However, others embraced the new narrative, suggesting radical ideas to prevent youth smoking. These ideas were not adopted. PMC's new narrative was unconvincing to many of its employees, who perceived it either as a threat to the company's continued profits or as incongruous with what they had previously been told. As it had done with the public, PMC misled its employees in explaining a narrative repositioning that would help the company continue business as usual. Moving toward a tobacco endgame will require ongoing discursive and symbolic efforts to disrupt this narrative.

  1. Foot-and-Mouth Disease Virus 2C Is a Hexameric AAA+ Protein with a Coordinated ATP Hydrolysis Mechanism

    DEFF Research Database (Denmark)

    Sweeney, Trevor; Cisnetto, Valentina; Bose, Daniel

    2010-01-01

    Foot-and-mouth disease virus (FMDV), a positive sense, single-stranded RNA virus, causes a highly contagious disease in cloven-hoofed livestock. Like other picornaviruses, FMDV has a conserved 2C protein assigned to the superfamily 3 helicases a group of AAA+ ATPases that has a predicted N-termin...

  2. Mineral fertilizer response and nutrient use efficiencies of East African highland banana (Musa spp., AAA-EAHB, cv. Kisansa)

    NARCIS (Netherlands)

    Nyombi, K.; Asten, van P.J.A.; Corbeels, M.; Taulya, G.; Leffelaar, P.A.; Giller, K.E.

    2010-01-01

    Poor yields of East African highland bananas (Musa spp., AAA-EAHB) on smallholder farms have often been attributed to problems of poor soil fertility. We measured the effects of mineral fertilizers on crop performance at two sites over two to three crop cycles; Kawanda in central Uganda and Ntungamo

  3. Fantasmes et fantômes dans Sabbath’s Theater, de Philip Roth (1995

    Directory of Open Access Journals (Sweden)

    Géraldine CHOUARD

    2003-06-01

    Full Text Available “We are dealing here with death, fuck the flowers!” (120 S’il fallait, dans la littérature américaine, mettre un nom en face du mot fantasme, ce serait celui de Philip Roth, dont l’œuvre se place sous le signe d’une formidable libido. Suivraient ensuite sans doute ceux de Nabokov, Miller, Bukowski, ou Updike qui ont tour à tour fait leur miel des fantasmes les plus divers. Regroupés autour de cette thématique, ces écrivains portent la fiction américaine à un taux de testostérone pour le moin...

  4. HTTP as a Data Access Protocol: Trials with XrootD in CMS’s AAA Project

    Science.gov (United States)

    Balcas, J.; Bockelman, B. P.; Kcira, D.; Newman, H.; Vlimant, J.; Hendricks, T. W.; CMS Collaboration

    2017-10-01

    The main goal of the project to demonstrate the ability of using HTTP data federations in a manner analogous to the existing AAA infrastructure of the CMS experiment. An initial testbed at Caltech has been built and changes in the CMS software (CMSSW) are being implemented in order to improve HTTP support. The testbed consists of a set of machines at the Caltech Tier2 that improve the support infrastructure for data federations at CMS. As a first step, we are building systems that produce and ingest network data transfers up to 80 Gbps. In collaboration with AAA, HTTP support is enabled at the US redirector and the Caltech testbed. A plugin for CMSSW is being developed for HTTP access based on the DaviX software. It will replace the present fork/exec or curl for HTTP access. In addition, extensions to the XRootD HTTP implementation are being developed to add functionality to it, such as client-based monitoring identifiers. In the future, patches will be developed to better integrate HTTP-over-XRootD with the Open Science Grid (OSG) distribution. First results of the transfer tests using HTTP are presented in this paper together with details about the initial setup.

  5. Philanthropy, politics and promotion: Philip Morris' "charitable contributions" in Thailand.

    Science.gov (United States)

    MacKenzie, Ross; Collin, Jeff

    2008-08-01

    The efforts of members of the tobacco industry to portray themselves as responsible corporations via ostensible commitment to improved labour practices and public philanthropy have attracted growing criticism. This is particularly true of corporate social responsibility (CSR) schemes undertaken in emerging nations that are designed to rehabilitate the tobacco industry's image among public, government and market opinions in North America and western Europe. In the case of Thailand, sponsorship of arts events and community groups has been one avenue of promoting the industry in a regulatory environment that severely curtails promotion and advertising. The Association of Southeast Asian Nations (ASEAN) Art Award, sponsored by Philip Morris (PM) has provided one such outlet for 10 years. Analysis of PM funding announcements since the end of the ASEAN art programme in Thailand reveals that recent donations to tobacco-related community organisations reinforces the extent to which seemingly generous acts are driven by corporate self-interest rather than social responsibility.

  6. Chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) with massive vertebral bone erosion. Computed tomography (CT), magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings

    International Nuclear Information System (INIS)

    Nakano, Sachiko; Okauchi, Kenzo; Tsushima, Yoshito

    2014-01-01

    A 62-year-old male presented with sudden onset of low back and right leg pain. Contrast-enhanced computed tomography demonstrated an abdominal aortic aneurysm (AAA), along with a large mass lesion causing vertebral body erosion. Magnetic resonance imaging (MRI) suggested that the mass lesion consisted of a chronic hematoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated increased uptake around the mass lesion, but not around the AAA. Surgical intervention was performed, and the subsequent histological diagnosis was chronic contained rupture of AAA. The mass lesion consisted of chronic hematoma and necrosis with inflammatory cell infiltration and hemosiderin deposition. This condition mimics some neoplastic diseases, but MRI and FDG-PET findings may help establish the correct diagnosis. (author)

  7. Läheneb Vikerkaare 75. aastapäev / Märt Väljataga

    Index Scriptorium Estoniae

    Väljataga, Märt, 1965-

    1997-01-01

    Vastukaja : Haug, Toomas. Kultuurilooline õppetund peatoimetaja Väljatagale. // Eesti Ekspress (1997) 18. apr., lk. B6. (Poleemika); Väljataga, Märt. Vikerkaart nähti juba Sumeris!. // Eesti Ekspress (1997) 25. apr., lk. B7; Haug, Toomas. Ei soovi vasikaga võidu joosta. // Eesti Ekspress (1997) 2. mai, lk. B7

  8. Katherine Philips, Aphra Behn, and Sylvia Plath: “a passionate journey” towards “a revolution in female manners”

    Directory of Open Access Journals (Sweden)

    Giada Cacciavilni

    2010-06-01

    Full Text Available Katherine Philips, Aphra Behn, and Sylvia Plath were artists who struggled during their lives to express their thoughts and ideas. In addition to this, being women, they found it hard to be recognised as writers and their fight against social conventions and norms is now considered of huge importance since they managed to open doors for women that came after them. Katherine Philips started a feminine revolution which was taken over by Aphra Behn, and by Sylvia Plath about three centuries later. The three authors rebelled against the feminine mystique of their time and the subsequent domestification of women. In addition to this, they refused to be men’s shadows and raised a new awareness of women as active subjects that could finally use their voices to express themselves. The aim of this essay is to explore and interpret the ways in which these three women managed to subvert the prescribed role that society had in store for them by touching on different topics related to gender and the relationship between men and women. I will focus on their outlook on marriage and on women’s roles in society.

  9. Validity of automated measurement of left ventricular ejection fraction and volume using the Philips EPIQ system.

    Science.gov (United States)

    Hovnanians, Ninel; Win, Theresa; Makkiya, Mohammed; Zheng, Qi; Taub, Cynthia

    2017-11-01

    To assess the efficiency and reproducibility of automated measurements of left ventricular (LV) volumes and LV ejection fraction (LVEF) in comparison to manually traced biplane Simpson's method. This is a single-center prospective study. Apical four- and two-chamber views were acquired in patients in sinus rhythm. Two operators independently measured LV volumes and LVEF using biplane Simpson's method. In addition, the image analysis software a2DQ on the Philips EPIQ system was applied to automatically assess the LV volumes and LVEF. Time spent on each analysis, using both methods, was documented. Concordance of echocardiographic measures was evaluated using intraclass correlation (ICC) and Bland-Altman analysis. Manual tracing and automated measurement of LV volumes and LVEF were performed in 184 patients with a mean age of 67.3 ± 17.3 years and BMI 28.0 ± 6.8 kg/m 2 . ICC and Bland-Altman analysis showed good agreements between manual and automated methods measuring LVEF, end-systolic, and end-diastolic volumes. The average analysis time was significantly less using the automated method than manual tracing (116 vs 217 seconds/patient, P Automated measurement using the novel image analysis software a2DQ on the Philips EPIQ system produced accurate, efficient, and reproducible assessment of LV volumes and LVEF compared with manual measurement. © 2017, Wiley Periodicals, Inc.

  10. Beneficial effect of statins on total mortality in abdominal aortic aneurysm (AAA) repair.

    Science.gov (United States)

    Mathisen, Sven Ross; Abdelnoor, Michael

    2017-10-01

    In this single center, retrospective cohort study we wished to compare early and total mortality for all patients treated for abdominal aortic aneurysms (AAA) with open surgery who were taking statins compared to those who were not. A cohort of 640 patients with AAA was treated with open surgery between 1999 and 2012. Patients were consecutively recruited from a source population of 390,000; 21.3% were female, and the median age was 73 years. The median follow-up was 3.93 years, with an interquartile range of 1.79-6.58 years. The total follow-up was 2855 patient-years. An explanatory strategy was used. The propensity score (PS) was implemented to control for selection bias and confounders. The crude effect of statin use showed a 78% reduction of the 30-day mortality. A stratified analysis using the Mantel-Haenszel method on quintiles of the PS gave an adjusted effect of the odds ratio equal to 0.43 (95% CI: 0.18-0.96), indicating a 57% reduction of the 30-day mortality for statin users. The adjusted rate ratio was 0.62 (95% CI: 0.45-0.83), indicating a reduction of long-term mortality of 38% for statin users compared to non-users for a median follow-up of 3.93 years. This retrospective cohort study showed a significant beneficial effect of statin use on early and long-term survival for patients treated with open surgery. To be conclusive, our results need to be replicated by a randomized clinical trial.

  11. The AAA-ATPase NVL2 is a telomerase component essential for holoenzyme assembly

    Energy Technology Data Exchange (ETDEWEB)

    Her, Joonyoung [Departments of Biology and Integrated Omics for Biomedical Science, Yonsei University, Seoul 120-749 (Korea, Republic of); Chung, In Kwon, E-mail: topoviro@yonsei.ac.kr [Departments of Biology and Integrated Omics for Biomedical Science, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Identification of the AAA-ATPase NVL2 as a novel hTERT-interacting protein. Black-Right-Pointing-Pointer NVL2 associates with catalytically active telomerase via an interaction with hTERT. Black-Right-Pointing-Pointer NVL2 is a telomerase component essential for holoenzyme assembly. Black-Right-Pointing-Pointer ATP-binding activity of NVL2 is required for hTERT binding and telomerase assembly. -- Abstract: Continued cell proliferation requires telomerase to maintain functional telomeres that are essential for chromosome integrity. Although the core enzyme includes a telomerase reverse transcriptase (TERT) and a telomerase RNA component (TERC), a number of auxiliary proteins have been identified to regulate telomerase assembly, localization, and enzymatic activity. Here we describe the characterization of the AAA-ATPase NVL2 as a novel hTERT-interacting protein. NVL2 interacts and co-localizes with hTERT in the nucleolus. NLV2 is also found in association with catalytically competent telomerase in cell lysates through an interaction with hTERT. Depletion of endogenous NVL2 by small interfering RNA led to a decrease in hTERT without affecting the steady-state levels of hTERT mRNA, thereby reducing telomerase activity, suggesting that NVL2 is an essential component of the telomerase holoenzyme. We also found that ATP-binding activity of NVL2 is required for hTERT binding as well as telomerase assembly. Our findings suggest that NVL2, in addition to its role in ribosome biosynthesis, is essential for telomerase biogenesis and provides an alternative approach for inhibiting telomerase activity in cancer.

  12. The New Secular Humanists: Ronald Dworkin and Philip Kitcher on Life without God

    Directory of Open Access Journals (Sweden)

    Charles Taliaferro

    2015-07-01

    Full Text Available Ronald Dworkin and Philip Kitcher recognize that traditional, religious faith—especially in Christian theistic tradition—has virtues that seem to be missing in a secular worldview. To remedy this apparent deficit, they both propose that a secular worldview can provide a satisfying foundation for a flourishing, meaningful life. Moreover, Kitcher argues that secular humanism is far more justified than a religious worldview because it does not face the problem of diversity that arises in the case of religion. I argue that secular humanism faces the same problem of diversity that Kitcher proposes undermines religious belief. I further argue that Dworkin’s and Kitcher’s secular alternative to a religious worldview is problematic.

  13. Evaluation of the penumbras of a Philips multileaf collimator

    Energy Technology Data Exchange (ETDEWEB)

    Lafay, F; Malet, C; Mombard, C; Ginestet, C [Centre de Lutte Contre le Cancer Leon-Berard, 69 - Lyon (France); Blondel, E [Isotec, Saint-Quentin (France); Desfarges, Y; Dupin, G [Philips Medical System, Lyon (France)

    1995-12-01

    Since January 1995, a Philips SL20 linear accelerator which is connected to a multileaf collimator has been used. Computer-controlled multileaf collimators open up the opportunity to practice conformal radiotherapy. Its aim is to adjust as well as possible the Planning Target Volume (PTV) to the effective treated volume with an homogeneous dose distribution in the PTV, and to protect healthy tissues and delicate organs. This is possible by means of a multileaf collimator by increasing the number of complex fields with different incidences during a same session. Moreover, the Beam`s Eye View function of the three-dimensional treatment planning system allows to define the shape of complex fields. For rectangular fields, the penumbra is defined by the distance between the 80% and 20% isodoses relative to the beam axis. In addition, the distances between, respectively, the 95% and 50% isodoses, the 90% and 50% isodoses, the 50% and 20% isodoses relative to the beam axis have been analysed. Different penumbras were evaluated. The result of this work will enable to adjust the reference isodose to the PTV either by integrating this result into dosimetry software, or by taking it into account for drawing the PTV.

  14. Evaluation of the penumbras of a Philips multileaf collimator

    International Nuclear Information System (INIS)

    Lafay, F.; Malet, C.; Mombard, C.; Ginestet, C.; Blondel, E.; Desfarges, Y.; Dupin, G.

    1995-01-01

    Since January 1995, a Philips SL20 linear accelerator which is connected to a multileaf collimator has been used. Computer-controlled multileaf collimators open up the opportunity to practice conformal radiotherapy. Its aim is to adjust as well as possible the Planning Target Volume (PTV) to the effective treated volume with an homogeneous dose distribution in the PTV, and to protect healthy tissues and delicate organs. This is possible by means of a multileaf collimator by increasing the number of complex fields with different incidences during a same session. Moreover, the Beam's Eye View function of the three-dimensional treatment planning system allows to define the shape of complex fields. For rectangular fields, the penumbra is defined by the distance between the 80% and 20% isodoses relative to the beam axis. In addition, the distances between, respectively, the 95% and 50% isodoses, the 90% and 50% isodoses, the 50% and 20% isodoses relative to the beam axis have been analysed. Different penumbras were evaluated. The result of this work will enable to adjust the reference isodose to the PTV either by integrating this result into dosimetry software, or by taking it into account for drawing the PTV

  15. Effect of microgravity simulation using 3D clinostat on cavendish banana (Musa acuminata AAA Group) ripening process

    Science.gov (United States)

    Dwivany, Fenny Martha; Esyanti, Rizkita R.; Prapaisie, Adeline; Puspa Kirana, Listya; Latief, Chunaeni; Ginaldi, Ari

    2016-11-01

    The objective of the research was to determine the effect of microgravity simulation by 3D clinostat on Cavendish banana (Musa acuminata AAA group) ripening process. In this study, physical, physiological changes as well as genes expression were analysed. The result showed that in microgravity simulation condition ripening process in banana was delayed and the MaACOl, MaACSl and MaACS5 gene expression were affected.

  16. The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors

    Science.gov (United States)

    Matias, Pedro M.; Baek, Sung Hee; Bandeiras, Tiago M.; Dutta, Anindya; Houry, Walid A.; Llorca, Oscar; Rosenbaum, Jean

    2015-01-01

    Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10–12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models. PMID:25988184

  17. The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.

    Science.gov (United States)

    Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean

    2015-01-01

    Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

  18. The skills of erect full-spine radiograph with Philips DR

    International Nuclear Information System (INIS)

    Yang Guangqi; Yang Xufeng; Wu Tengfang; Wen Xingwei

    2009-01-01

    Objective: To investigate the image stitching methods and skills of erect full-spine P-A radiograph with Philips DR. Methods: Proper spinal projecting position and exposure factors were selected to get the radiogragh of full-spine. Three methods were used to stitch images. The image deviation was evaluated with photoshop to judge the quality of the stitching full-spine images. Results: Among ninety-eight patients, the full-spine images were stitched successfully by automatic method in 78 patients. Other stiching images were justified with manual stitching method and were good enough for diagnosis. The border of vertebral body, pedicle of vertebral arch and spinous process were revealed clearly in 96 patients. The shift of vertebral body at stitching point was within 1 mm in 83 patients, 2mm in 11 patients, 3mm in 2 patients. Conclusion: Full spine radiography with DDR can provide clinical diagnosis information with reliable images. High quality and reliable full-spine images can be got with proper spinal projecting position, appropriate image postprocess software and suitable stitching method. (authors)

  19. AAA and PBC calculation accuracy in the surface build-up region in tangential beam treatments. Phantom and breast case study with the Monte Carlo code PENELOPE

    International Nuclear Information System (INIS)

    Panettieri, Vanessa; Barsoum, Pierre; Westermark, Mathias; Brualla, Lorenzo; Lax, Ingmar

    2009-01-01

    Background and purpose: In tangential beam treatments accurate dose calculation of the absorbed dose in the build-up region is of major importance, in particular when the target has superficial extension close to the skin. In most analytical treatment planning systems (TPSs) calculations depend on the experimental measurements introduced by the user in which accuracy might be limited by the type of detector employed to perform them. To quantify the discrepancy between analytically calculated and delivered dose in the build-up region, near the skin of a patient, independent Monte Carlo (MC) simulations using the PENELOPE code were performed. Dose distributions obtained with MC simulations were compared with those given by the Pencil Beam Convolution (PBC) algorithm and the Analytical Anisotropic Algorithm (AAA) implemented in the commercial TPS Eclipse. Material and methods: A cylindrical phantom was used to approximate the breast contour of a patient for MC simulations and the TPS. Calculations of the absorbed doses were performed for 6 and 18 MV beams for four different angles of incidence: 15 deg., 30 deg., 45 deg. and 75 deg. and different field sizes: 3 x 3 cm 2 , 10 x 10 cm 2 and 40 x 40 cm 2 . Absorbed doses along the phantom central axis were obtained with both the PBC algorithm and the AAA and compared to those estimated by the MC simulations. Additionally, a breast patient case was calculated with two opposed 6 MV photon beams using all the aforementioned analytical and stochastic algorithms. Results: For the 6 MV photon beam in the phantom case, both the PBC algorithm and the AAA tend to underestimate the absorbed dose in the build-up region in comparison to MC results. These differences are clinically irrelevant and are included in a 1 mm range. This tendency is also confirmed in the breast patient case. For the 18 MV beam the PBC algorithm underestimates the absorbed dose with respect to the AAA. In comparison to MC simulations the PBC algorithm tends

  20. A comparison between Philips and Tomtec for left ventricular deformation and volume measurements in neonatal intensive care patients.

    Science.gov (United States)

    de Waal, Koert; Phad, Nilkant

    2018-03-01

    Two-dimensional speckle tracking echocardiography is an emerging technique for analyzing cardiac function in newborns. Strain is a highly reliable and reproducible parameter, and reference values have been established for term and preterm newborns. Its implementation into clinical practice has been slow, partly due to lack of inter-vendor consistency. Our aim was to compare recent versions of Philips and Tomtec speckle tracking software for deformation and semiautomated volume and area measurements in neonatal intensive care patients. Longitudinal and circumferential deformation and cavity dimensions (volume, area) were determined off line from apical and short-axis images in 50 consecutive newborns with a median birthweight of 760 g (range 460-3200 g). Absolute mean endocardial global longitudinal strain measurements were similar between vendors, but with wide limits of agreement (Philips -18.9 [2.1]%, Tomtec -18.6 [2.5]%, bias -0.3 [1.7]%, and limits of agreement -3.6%-3.1%). Longitudinal strain rate and circumferential measurements showed poor correlation. All volume and area measurements correlated well between the vendors, but with significant bias. Global longitudinal strain measurements compared well between vendors but wide limits of agreement, suggesting that longitudinal measurements are preferred using similar hardware and software. © 2017, Wiley Periodicals, Inc.

  1. Dosimetric accuracy and clinical quality of Acuros XB and AAA dose calculation algorithm for stereotactic and conventional lung volumetric modulated arc therapy plans

    International Nuclear Information System (INIS)

    Kroon, Petra S; Hol, Sandra; Essers, Marion

    2013-01-01

    The main aim of the current study was to assess the dosimetric accuracy and clinical quality of volumetric modulated arc therapy (VMAT) plans for stereotactic (stage I) and conventional (stage III) lung cancer treatments planned with Eclipse version 10.0 Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) algorithm. The dosimetric impact of using AAA instead of AXB, and grid size 2.5 mm instead of 1.0 mm for VMAT treatment plans was evaluated. The clinical plan quality of AXB VMAT was assessed using 45 stage I and 73 stage III patients, and was compared with published results, planned with VMAT and hybrid-VMAT techniques. The dosimetric impact on near-minimum PTV dose (D 98% ) using AAA instead of AXB was large (underdose up to 12.3%) for stage I and very small (underdose up to 0.8%) for stage III lung treatments. There were no significant differences for dose volume histogram (DVH) values between grid sizes. The calculation time was significantly higher for AXB grid size 1.0 than 2.5 mm (p < 0.01). The clinical quality of the VMAT plans was at least comparable with clinical qualities given in literature of lung treatment plans with VMAT and hybrid-VMAT techniques. The average mean lung dose (MLD), lung V 20Gy and V 5Gy in this study were respectively 3.6 Gy, 4.1% and 15.7% for 45 stage I patients and 12.4 Gy, 19.3% and 46.6% for 73 stage III lung patients. The average contra-lateral lung dose V 5Gy-cont was 35.6% for stage III patients. For stereotactic and conventional lung treatments, VMAT calculated with AXB grid size 2.5 mm resulted in accurate dose calculations. No hybrid technique was needed to obtain the dose constraints. AXB is recommended instead of AAA for avoiding serious overestimation of the minimum target doses compared to the actual delivered dose

  2. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ.

    Science.gov (United States)

    Zhang, Yahui; Li, Wanjie; Chu, Mi; Chen, Hengye; Yu, Haoyuan; Fang, Chaoguang; Sun, Ningze; Wang, Qiming; Luo, Tian; Luo, Kaiju; She, Xueping; Zhang, Mengqian; Yang, Dong

    2016-06-01

    Candida albicans is an opportunistic human pathogen, and its pathogenicity is associated with hyphal formation. Previous studies have shown that at neutral-to-alkaline pH, hyphal growth is dependent on the Rim101 pathway whose activation requires Snf7, a member of the ESCRT system. In this work, we described the purification and characterization of the C. albicans Vps4, an AAA ATPase required for recycling of the ESCRTs. Its role on hyphal growth has been investigated. Our data suggest deletion of Vps4 decreases overall hyphal growth at pH 7 and increases the growth of multiple hyphae induced by serum, which indicates that the ESCRTs may make a Rim101-independent contribution to hyphal growth. Furthermore, DBeQ, an inhibitor of the AAA ATPase p97, was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. Our work may provide a new strategy to control C. albicans infection.

  3. When Harry met Zuckerman: self-reflexivity and metafiction in Philip Roth and Woody Allen

    Directory of Open Access Journals (Sweden)

    Thomás Creus

    2006-04-01

    Full Text Available The objective of this essay is to compare the works of novelist Philip Roth and film-maker Woody Allen in what regards their treatment of the highly complex theme of the interrelations between fiction and reality. A comparative analysis of selected Roth’s novels and Allen’s films evinces their recurrent preoccupation with the creation of art and its implications, be it through the choice of writers or artists as main characters, be it through plots that mix real facts with invented ones and imaginary characters with real ones, be it through the use of autobiographical elements in a fictional discourse—all metafictional devices that call attention to the artist’s own process of creation.

  4. Cotranslocational processing of the protein substrate calmodulin by an AAA+ unfoldase occurs via unfolding and refolding intermediates.

    Science.gov (United States)

    Augustyniak, Rafal; Kay, Lewis E

    2018-05-22

    Protein remodeling by AAA+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT AAA+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.

  5. Commentary on Adele Tutter's "Design as dream and self-representation: Philip Johnson and the Glass House of Atreus".

    Science.gov (United States)

    Danze, Elizabeth A; Sonnenberg, Stephen M

    2012-06-01

    In this discussion of Adele Tutter's "Design as Dream and Self-Representation: Philip Johnson and the Glass House of Atreus" (JAPA 59/3), the architect Elizabeth Danze and the psychoanalyst Stephen Sonnenberg highlight what they see as the most important of Tutter's contributions as regards an understanding of Johnson's work. They then discuss those contributions as they illuminate the study of the relationship of architecture and design, on the one hand, and psychoanalysis on the other.

  6. SU-F-SPS-01: Accuracy of the Small Field Dosimetry Using Acuros XB and AAA Dose Calculation Algorithms of Eclipse Treatment Planning System Within and Beyond Heterogeneous Media for Trubeam 2.0 Unit

    International Nuclear Information System (INIS)

    Codel, G; Serin, E; Pacaci, P; Sanli, E; Cebe, M; Mabhouti, H; Doyuran, M; Kucukmorkoc, E; Kucuk, N; Altinok, A; Canoglu, D; Acar, H; Caglar Ozkok, H

    2016-01-01

    Purpose: In this study, the comparison of dosimetric accuracy of Acuros XB and AAA algorithms were investigated for small radiation fields incident on homogeneous and heterogeneous geometries Methods: Small open fields of Truebeam 2.0 unit (1×1, 2×2, 3×3, 4×4 fields) were used for this study. The fields were incident on homogeneous phantom and in house phantom containing lung, air, and bone inhomogeneities. Using the same film batch, the net OD to dose calibration curve was obtaine dusing Trubeam 2.0 for 6 MV, 6 FFF, 10 MV, 10 FFF, 15 MV energies by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. The dosimetric accuracy of Acuros XB and AAA algorithms in the presence of the inhomogeneities was compared against EBT3 film dosimetry Results: Open field tests in a homogeneous phantom showed good agreement betweent wo algorithms and measurement. For Acuros XB, minimum gamma analysis passin grates between measured and calculated dose distributions were 99.3% and 98.1% for homogeneousand inhomogeneous fields in thecase of lung and bone respectively. For AAA, minimum gamma analysis passingrates were 99.1% and 96.5% for homogeneous and inhomogeneous fields respectively for all used energies and field sizes.In the case of the air heterogeneity, the differences were larger for both calculations algorithms. Over all, when compared to measurement, theAcuros XB had beter agreement than AAA. Conclusion: The Acuros XB calculation algorithm in the TPS is an improvemen tover theexisting AAA algorithm. Dose discrepancies were observed for in the presence of air inhomogeneities.

  7. SU-F-SPS-01: Accuracy of the Small Field Dosimetry Using Acuros XB and AAA Dose Calculation Algorithms of Eclipse Treatment Planning System Within and Beyond Heterogeneous Media for Trubeam 2.0 Unit

    Energy Technology Data Exchange (ETDEWEB)

    Codel, G; Serin, E; Pacaci, P; Sanli, E; Cebe, M; Mabhouti, H; Doyuran, M; Kucukmorkoc, E; Kucuk, N; Altinok, A; Canoglu, D; Acar, H; Caglar Ozkok, H [Medipol University, Istanbul, Istanbul (Turkey)

    2016-06-15

    Purpose: In this study, the comparison of dosimetric accuracy of Acuros XB and AAA algorithms were investigated for small radiation fields incident on homogeneous and heterogeneous geometries Methods: Small open fields of Truebeam 2.0 unit (1×1, 2×2, 3×3, 4×4 fields) were used for this study. The fields were incident on homogeneous phantom and in house phantom containing lung, air, and bone inhomogeneities. Using the same film batch, the net OD to dose calibration curve was obtaine dusing Trubeam 2.0 for 6 MV, 6 FFF, 10 MV, 10 FFF, 15 MV energies by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. The dosimetric accuracy of Acuros XB and AAA algorithms in the presence of the inhomogeneities was compared against EBT3 film dosimetry Results: Open field tests in a homogeneous phantom showed good agreement betweent wo algorithms and measurement. For Acuros XB, minimum gamma analysis passin grates between measured and calculated dose distributions were 99.3% and 98.1% for homogeneousand inhomogeneous fields in thecase of lung and bone respectively. For AAA, minimum gamma analysis passingrates were 99.1% and 96.5% for homogeneous and inhomogeneous fields respectively for all used energies and field sizes.In the case of the air heterogeneity, the differences were larger for both calculations algorithms. Over all, when compared to measurement, theAcuros XB had beter agreement than AAA. Conclusion: The Acuros XB calculation algorithm in the TPS is an improvemen tover theexisting AAA algorithm. Dose discrepancies were observed for in the presence of air inhomogeneities.

  8. Avian Diseases: The Creation and Evolution of P. Philip Levine's Enduring Gift.

    Science.gov (United States)

    Calnek, Bruce W

    2015-03-01

    This account has two aims. The first is to provide a tribute to Dr. Pincus Philip Levine, the founder of Avian Diseases. It addresses several facets of the life and times of this remarkable and interesting personality, giving some insight into the why and how he came to establish the journal. It touches on his background; his character; his astute and searching mind; his ability to interact with others; his influence on veterinary, and especially avian, medicine; and his teaching genius and reveals the positive force he was in his interactions with others. Then, it turns to a celebration of the first half-century of the journal that he created, essentially single-handedly, and reviews some of the history regarding the stimulus, birthing pains, and gradual evolution of the journal through a succession of editors, business managers, and supporting casts to the publication that we see today, nearly 50 yr later.

  9. The AAA+ ATPase p97, a cellular multitool.

    Science.gov (United States)

    Stach, Lasse; Freemont, Paul S

    2017-08-17

    The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. © 2017 The Author(s).

  10. Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B).

    Science.gov (United States)

    Gao, Peng; Si, Jiyuan; Yang, Bin; Yu, Jixiang

    2017-02-18

    BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors. RESULTS We found that CDKN2B was a virtual target of miR-15a-5p with potential binding sites in the 3'UTR of CDKN2B (77-83 bp). We also showed that miR-15a-5p could bind to the CDKN2B 3'UTR, resulting in a significant decrease in luciferase activity compared with the scramble control. Furthermore, we found that the cells isolated from AAA participants showed an over-expression of miR-15a-5p compared to the normal controls, while the CDKN2B mRNA and protein expression level of the AAA group were much lower than the normal control group. Additionally, the expression of CDKN2B mRNA and the protein of the cells transfected with miR-15a-5p mimics and CDKN2B siRNA was downregulated, while the cells showed upregulated expression subsequent to transfection with miR-15a-5p inhibitors compared to the scramble control. CONCLUSIONS The data revealed a negative regulatory role of miR-15a-5p in the apoptosis of smooth muscle cells via targeting CDKN2B, and showed that miR-15a-5p could be a novel therapeutic target of AAA.

  11. Toxicidad de boro en plantaciones de banano(Musa AAA en Costa Rica

    Directory of Open Access Journals (Sweden)

    Alfonso Vargas

    2007-01-01

    Full Text Available En las hojas de plantas de banano (Musa AAA, cvs. Grande Naine y Valery, se observó una necrosis marginal irregular y continua, la cual se desarrolló a partir de un área clorótica igualmente irregular, que avanzó del margen hacia el interior de la hoja. La parte central de la lámina foliar retuvo siempre su coloración verde original. Los análisis de suelo y tejido foliar mostraron que los síntomas fueron causados por altas concentraciones de boro, debido ya fuese a aplicaciones excesivas del nutrimento al suelo y al follaje, o por el efecto de aplicaciones muy frecuentes de boro vía fertirriego, combinado con una disminución de la concentración de calcio en la hoja

  12. EFECTO DE LA MICORRIZACIÓN Y LA FERTILIZACIÓN EN LA ACUMULACIÓN DE BIOMASA EN PLANTAS DE BANANO (Musa AAA cv. Gran Enano (Musaceae MICORRHIZATION AND FERTILIZATION EFFECT ON BIOMASS ACCUMULATION IN BANANA PLANTS (Musa AAA cv. Gran Enano (Musaceae

    Directory of Open Access Journals (Sweden)

    Carmen Elena Usuga Osorio

    2008-06-01

    Full Text Available Bajo condiciones de invernadero (ubicado en el municipio de Bello - Antioquia (Colombia se evaluó el efecto independiente y combinado de los factores: tipo de inóculo de Hongos Micorriza Arbuscular (HMA, fertilización y aplicación de materia orgánica sobre el porcentaje de asociación de HMA en plantas de banano (Musa AAA cv. Gran Enano, así como en la acumulación de materia seca foliar y radical. Dentro del factor tipo de inóculo, se evaluaron inóculos nativos, de agroecosistemas bananeros y ecosistemas naturales del Urabá (Antioquia-Colombia, uno comercial y la especie Acaulospora morrowiae; con respecto a la fertilización se probó la mitad, completa y dos veces la dosis de la fertilización recomendada de acuerdo al análisis de suelo y a los requerimientos de la planta, y cada uno de estos factores con y sin la aplicación de materia orgánica; como testigos se usaron, la no aplicación del respectivo factor. Se usó como material vegetal plantas de banano micropropagadas del grupo Cavendish cv. Gran Enano (AAA. El sustrato utilizado para el crecimiento de las plantas de banano se compuso de suelo y arena en relación 70/30 v/v. El suelo se obtuvo de la granja experimental de Augura, ubicado en el municipio de Carepa en la región de Urabá. Los resultados encontrados, muestran que los factores que más incidieron en la asociación así como en la acumulación de biomasa en toda la planta son la micorrización y la adición de materia orgánica. Los resultados, también muestran un comportamiento positivo respecto al uso de inóculos nativos de agroecosistemas bananeros, con bajas aplicaciones de fertilizantes.The effects of independent an combined factors such as inoculum type, fertilization and organic matter application on the percentage of association of ‘H.M.A’ in banana plants (Musa AAA cv. ‘Gran Enano’, and on the accumulation of leaves and rrots material, were evaluated under greenhouse conditions. Natives samples

  13. The Character as Text in Philip Massinger’s A New Way to Pay Old Debts Le Personnage comme texte dans A New Way to Pay Old Debts de Philip Massinger

    Directory of Open Access Journals (Sweden)

    Wendy Ribeyrol

    2009-06-01

    Full Text Available Dans A New Way to Pay Old Debts de Philip Massinger la réputation est perçue comme une feuille blanche sur laquelle le personnage doit écrire le récit de sa vie. L’idée de la vie d’un homme comme livre ou comme feuille de papier est fort ancienne, elle figure aussi bien dans la Bible que dans les livres d’emblèmes des XVIe et XVIIe siècles. Au moment de la mort, l’homme laisse ainsi à la postérité un texte édifiant dont il aura été l’auteur (auctor. Cet article démontre  qu’il faut néanmoins faire une distinction entre l’homme, qui prend plume et rédige son propre texte, et la femme qui doit attendre passivement qu’un autre compose le sien.

  14. 9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.

    Science.gov (United States)

    Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew

    2016-11-01

    The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.

  15. The utility of the Philips SRI-100 real time portal imaging device in a case of postoperative irradiation for prevention of heterotopic bone formation following total hip replacement

    International Nuclear Information System (INIS)

    Kiffer, J.D.; Quong, G.; Lawlor, M.; Schumer, W.; Aitken, L.; Wallace, A.

    1994-01-01

    The new Radiation Oncology Department at the Heidelberg Repatriation Hospital in Melbourne, Australia commenced operation in June 1992. As part of quality control the Philips SL-15 linear accelerator was fitted with the Philips SRI-100 Real Time Portal Imaging Device (RTPID), the first such apparatus in Australia. One of its major advantages over older systems is its ability to provide a permanent hard copy of the image of the field treated. The computer image can be immediately manipulated and enhanced on the screen (with respect to such qualities as brightness and contrast) prior to the printing of the hard copy. This is a significant improvement over the more cumbersome older port films that required developing time, without any pre-assessment of the image quality. The utility of the Philips SRI-100 RTPID is demonstrated in the case of a patient irradiated soon after total hip replacement, as prophylaxis against heterotopic bone formation (HBF). The rapidity and quality of image production is a major advantage in these patients where post operative pain may result in positional change between film exposure and image production. Extremely accurate shielding block position is essential to shield the prosthesis(and allow bone ingrowth for fixation) whilst avoiding inadvertent shielding of the areas at risk for HBF. A review of the literature on this topic is provided. 14 refs., 4 figs

  16. The Protective Effects of Diabetes Mellitus on Post-EVAR AAA Growth and Reinterventions.

    Science.gov (United States)

    Png, Chien Yi M; Tadros, Rami O; Kang, Ming; Beckerman, William E; Tardiff, Melissa L; Vouyouka, Ageliki G; Marin, Michael L; Faries, Peter L

    2017-08-01

    This study aims to investigate the effect of diabetes on post-endovascular aneurysm repairs (EVARs) of abdominal aortic aneurysms (AAAs). A total of 1,479 consecutive patients who underwent AAA EVAR were reviewed. The cohorts were divided based on their diabetes status and compared. Preoperative demographic and comorbidity data were analyzed using the t-test and chi-squared test, whereas post-EVAR outcomes were analyzed using Probit multivariate model, followed by Kaplan-Meier survival curve and Cox regression. Of our 1,479 patients, 993 met inclusion criteria. One hundred eighty-three were diabetics (18.4%) compared with 810 nondiabetics (81.6%). Coronary artery disease (CAD; diabetics: 70.49%, nondiabetics: 60.76%, P = 0.014) and hypertension (HTN; diabetics: 90.16%, nondiabetics: 79.46%, P = 0.0008) were the only comorbidities analyzed, including follow-up length, which had any significant differences between the diabetic and nondiabetic groups. Probit multivariate analysis using a combined cohort follow-up mean of 51 months showed a significant decrease in aneurysm sac enlargement in diabetic patients (diabetics: 13.11%, nondiabetics: 19.43%, model estimate: 0.3058; 95% confidence interval [CI]: 0.0486-0.5629, Pr > ChiSq = 0.0198) and trended toward significantly fewer reinterventions (diabetics: 23.50%, nondiabetics: 28.41%, model estimate: 0.1990; 95% CI: -0.0262 to 0.4243, Pr > ChiSq = 0.0833). In the Cox regressions, diabetes had a significant protective factor on reinterventions (hazard ratio [HR]: 0.697, Pr > ChiSq = 0.0151), and was trending toward significance for aneurysm sac enlargement (HR: 0.750, Pr > ChiSq = 0.1961). There was no significant difference across diabetic status in any other outcomes, including mortality and endoleak occurrence. Although a higher proportion of diabetic patients present with HTN and CAD, they have decreased long-term rates of aneurysm sac enlargement after EVAR. As a result, this cohort trends

  17. Quentin Skinner, Staten og friheten. Oslo: Res Publica, 2011. José Luis Martí and Philip Pettit, A Political Philosophy in Public Life. Civic Republicanism in Zapatero's Spain. Princeton: Princeton University Press, 2010 (Simon Laumann Jørgensen)

    DEFF Research Database (Denmark)

    Jørgensen, Simon Laumann

    2012-01-01

    Anmeldelse af Quentin Skinner, Staten og friheten, Oslo: Res Publica 2011, 199 NOK & José Luis Martí & Philip Pettit, A Political Philosophy in Public Life. Civic Republicanism in Zapatero’s Spain, Princeton: Princeton University Press 2010, $ 24.95......Anmeldelse af Quentin Skinner, Staten og friheten, Oslo: Res Publica 2011, 199 NOK & José Luis Martí & Philip Pettit, A Political Philosophy in Public Life. Civic Republicanism in Zapatero’s Spain, Princeton: Princeton University Press 2010, $ 24.95...

  18. Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy.

    Science.gov (United States)

    Yeung, Heidi O; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S

    2014-03-05

    The type II AAA+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes.

  19. Proposal for a heavy ion ECR-source at the PSI-Philips cyclotron

    International Nuclear Information System (INIS)

    Kern, J.

    1989-10-01

    It is proposed by a large community of PSI- and external scientists to install an electron cyclotron resonance (ECR) source for highly charged heavy ions at the PHILIPS (injector I) cyclotron. Such a facility would then allow to produce high intensity ion beams with energies up to 30 MeV/u. A workshop hold in June 1989 clearly showed that with such a machine a large variety of interesting heavy ion experiments could be performed. While at foreign heavy ion centres the main focus is given to basic research in the field of nuclear physics we propose to concentrate the scientific effort at a PSI heavy ion facility mainly onto applications in the fields of atomic physics, chemistry, accelerator mass spectrometry, radiation biology and solid state physics. This is adequate, in view of the broad infrastructure available at PSI together with the existing know-how in many different fields. The proposed machine will thus be of great potential use for a large community. (author) 19 figs., 3 tabs., 82 refs

  20. Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency.

    Science.gov (United States)

    Parsons, Barbara L; Delongchamp, Robert R; Beland, Frederick A; Heflich, Robert H

    2006-01-01

    DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA-->AAA mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA-->AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA-->AAA mutational response induced by 4-ABP.

  1. Radiation dose assessment of musa acuminata - triploid (AAA)

    International Nuclear Information System (INIS)

    Maravillas, Mart Andrew S.; Locaylocay, Jocelyn R.; Mendoza, Concepcion S.

    2008-01-01

    Bananas are radioactive due to the presence of the radioisotope- 40 K. This imposes a possible health risk to the general public. This study intended to assess the annual equivalent dosages and the annual effective dosage committed by the body. This seeks to benefit the general public, students and researchers, and entrepreneurs. Using atomic absorption spectrophotometry, lakatan banana (Musa acuminata-triploid (AAA), the most purchased variety cultivated in Barangay Adlawon, Cebu City, Philippines, was found to contain 0.53 g of total potassium for every 100 g of its fresh fruit wherein 6.2 x 10 -5 g of which is potassium-40. Based on its 40 K content banana was calculated to have a radioactivity of 16 Bq/100 g. it was found out that the body is exposed to radiation dosages ranging from 2.8 x 10 -3 rem annually by eating 100 g of lakatan bananas everyday. Conversely, it is equivalent to the annual effective dosage of 0.0043 rem; the amount at which the body of an individual is uniformly exposed. However, no or extremely minute health risk was determined by just eating bananas. In fact, to exceed the radiation dose limits set by the International Commission on Radiation Protection, an individual may eat 116 kg of lakatan bananas everyday for a year. Fertilizers may be the major source of the radioisotope - 40 K and assimilated by the plants. (author)

  2. Functional renal perfusion imaging with colour mapping: is it a useful adjunct to spiral CT of in the assessment of abdominal aortic aneurysm (AAA)?

    International Nuclear Information System (INIS)

    Blomley, Martin J.K.; McBride, Alan; Mohammedtagi, Sima; Albrecht, Thomas; Harvey, Christopher J.; Jaeger, Rolf; Standfield, Nigel J.; Dawson, Peter

    1999-01-01

    Aim: To ensure optimal timing with pre-operative spiral CT for abdominal aortic aneurysms (AAA), an initial 'timing' single level CT is commonly performed with a small bolus of contrast. This can be exploited to obtain adjunct functional information on renal perfusion. We have investigated the potential of this to measure renal perfusion, to produce colour renal perfusion maps and to predict surgical outcome in infrarenal aortic aneurysm assessment. Methods: We studied 21 patients being assessed for repair of infrarenal AAA. Prior to the spiral CT, a single level through the renal hili and aorta was scanned after the intravenous injection of 25 ml of contrast given at 10 ml/s. Ten 1 s duration scans were performed from 8 to 30 s after injection. Optimal timing for CT angiography can then be determined. Time-density curves were then drawn for both kidneys and aorta using regions of interest (ROIs) or pixel-by-pixel analysis. Renal cortical perfusion was measured using both ROI analysis and pseudocolour perfusion images. Following previous work, perfusion was calculated as the peak upslope of the tissue time density curve divided by peak aortic enhancement. Results: Cortical mean perfusion averaged 2.48 ml/min per ml (range 0.8-3.7 ml/min per ml n=34) and the values obtained agreed with literature expectations. Follow up in the 10 patients proceeding to AAA repair suggest low mean perfusion values and predict a raised postoperative creatinine (P<0.05) Conclusions: Additional functional data and imaging can be obtained from the initial timing scan of a CT study, without requiring a dedicated study

  3. Improving Hearing Aid Self-Efficacy and Utility Through Revising a Hearing Aid User Guide: A Pilot Study.

    Science.gov (United States)

    McMullan, Alexandra; Kelly-Campbell, Rebecca J; Wise, Kim

    2018-03-08

    This pilot study aimed to investigate whether revising a hearing aid user guide (HAUG) is associated with improved hearing aid self-efficacy and utility performance. In Part 1, an HAUG was evaluated using the Suitability Assessment of Material (SAM) and readability formulas (Flesch Reading Ease [Flesch, 1943], Flesch-Kincaid Readability Formula [Kincaid, Fishburne, Rogers, & Chissom, 1957], and Simple Measure of Gobbledygook [McLaughlin, 1969]). The HAUG was revised using results from the SAM and best practice guidelines. The revision included generating a video. In Part 2, 30 adults with hearing impairment were randomly assigned to use either the original guide (N = 15) or the revised guide and video (N = 15) to perform a utility task. Participants' self-efficacy was measured using the Basic and Advanced Handling subscales of the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids questionnaire. SAM and readability were compared between the original and revised guides (Doak, Doak, & Root, 1996). SAM and readability were improved following the revision. Participants in the revised guide group performed significantly better on the utility task and on the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids subscales than participants in the original guide group. These results are encouraging as they indicate that there is scope to influence self-efficacy and utility performance through the use of appropriate HAUGs.

  4. DnaA protein DNA-binding domain binds to Hda protein to promote inter-AAA+ domain interaction involved in regulatory inactivation of DnaA.

    Science.gov (United States)

    Keyamura, Kenji; Katayama, Tsutomu

    2011-08-19

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.

  5. DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-AAA+ Domain Interaction Involved in Regulatory Inactivation of DnaA*

    Science.gov (United States)

    Keyamura, Kenji; Katayama, Tsutomu

    2011-01-01

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944

  6. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    Energy Technology Data Exchange (ETDEWEB)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

    2015-11-20

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  7. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    International Nuclear Information System (INIS)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami

    2015-01-01

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  8. Novel essential residues of Hda for interaction with DnaA in the regulatory inactivation of DnaA: unique roles for Hda AAA Box VI and VII motifs.

    Science.gov (United States)

    Nakamura, Kenta; Katayama, Tsutomu

    2010-04-01

    Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra-initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153) and DnaA sensor II Arg-334 within each AAA(+) domain are crucial for the DnaA-ATP hydrolysis. Here, we demonstrate that direct and functional interaction of ADP-Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the DnaA Walker B motif region, in addition to an intramolecular interaction between Hda Asn-122 and Arg-153. These interactions likely sustain a specific association of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and electrostatic features are basically conserved in the corresponding residues of other AAA(+) proteins, suggesting a conserved role for Box VI. These findings indicate novel interaction mechanisms for Hda-DnaA as well as a potentially fundamental mechanism in AAA(+) protein interactions.

  9. Uranium hydrogeochemical and stream sediment reconnaissance of the Philip Smith Mountains NTMS quadrangle, Alaska

    International Nuclear Information System (INIS)

    1981-09-01

    Results of a hydrogeochemical and stream sediment reconnaissance of the Philip Smith Mountains NTMS quadrangle, Alaska are presented. In addition to this abbreviated data release, more complete data are available to the public in machine-readable form. In this data release are location data, field analyses, and laboratory analyses of several different sample media. For the sake of brevity, many field site observations have not been included in this volume. These data are, however, available on the magnetic tape. Appendices A and B describe the sample media and summarize the analytical results for each medium. The data were subsetted by one of the Los Alamos National Laboratory (LANL) sorting programs into groups of stream sediment and lake sediment samples. For each group which contains a sufficient number of observations, statistical tables, tables of raw data, and 1:1000000 scale maps of pertinent elements have been included in this report

  10. Uranium hydrogeochemical and stream sediment reconnaissance of the Philip Smith Mountains NTMS quadrangle, Alaska

    Energy Technology Data Exchange (ETDEWEB)

    1981-09-01

    Results of a hydrogeochemical and stream sediment reconnaissance of the Philip Smith Mountains NTMS quadrangle, Alaska are presented. In addition to this abbreviated data release, more complete data are available to the public in machine-readable form. In this data release are location data, field analyses, and laboratory analyses of several different sample media. For the sake of brevity, many field site observations have not been included in this volume. These data are, however, available on the magnetic tape. Appendices A and B describe the sample media and summarize the analytical results for each medium. The data were subsetted by one of the Los Alamos National Laboratory (LANL) sorting programs into groups of stream sediment and lake sediment samples. For each group which contains a sufficient number of observations, statistical tables, tables of raw data, and 1:1000000 scale maps of pertinent elements have been included in this report.

  11. Postural stabilizing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) compared with calcium carbonate assessed by computerized posturography.

    Science.gov (United States)

    Fujita, Takuo; Nakamura, Shoji; Ohue, Mutsumi; Fujii, Yoshio; Miyauchi, Akimitsu; Takagi, Yasuyuki; Tsugeno, Hirofumi

    2007-01-01

    Sway and postural instability have drawn attention as a risk factor for osteoporotic fracture, in addition to low bone mineral density (BMD) and poor bone quality. In view of the fracture-reducing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) not readily explained by rather mild increases of BMD, attempts were made to evaluate postural stabilizing effect of alfacalcidol, AAA Ca, and calcium carbonate (CaCO(3)) by computerized posturography. Track of the gravity center was analyzed to calculate parameters related to tract length, track range, and track density to express the degree of sway before and after supplementation in 126 subjects ranging in age between 20 and 81 years randomly divided into four groups. Supplementation with AAA Ca containing 900 mg elemental Ca (group A), no calcium (group B), CaCO(3) also containing 900 mg elemental Ca (group C), or alfacalcidol (group D) continued daily for 12 months. For each parameter, the ratio closed eye value/open eye value (Romberg ratio) was calculated to detect aggravation of sway by eye closure. Age, parameters of Ca and P, and proportions of subjects with fracture and those with low BMD showed no marked deviation among the groups. With eyes open, significant decreases of a track range parameter (REC) from group B was noted in groups A (P = 0.0397) and D (P = 0.0296), but not in group C according to multiple comparison by Scheffe, indicating superior postural stabilizing effect of A and D over C. In the first 2 months, a significant fall was already evident in REC from group B in group D (P = 0.0120) with eyes open. Paired comparison of sway parameters before and after supplementation revealed a significant increase of track density parameter (LNGA), indicating sway control efficiency and a significant decrease of REC in groups A and D compared to group B with eyes open. With eyes closed, only group A showed a significant improvement from group B (P = 0.0456; Fig. 1), with a significant

  12. 2013 Philip S. Portoghese Medicinal Chemistry Lectureship: Drug Discovery Targeting Allosteric Sites†

    Science.gov (United States)

    2015-01-01

    The identification of sites on receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and modes of pharmacology for target modulation. Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numerous advantages, as well as caveats (e.g., flat structure–activity relationships, species differences, “molecular switches”), have been identified. For multiple receptors and proteins, numerous examples have been described where unprecedented levels of selectivity are achieved along with improved physiochemical properties. While not a panacea, these novel approaches represent exciting opportunities for tool compound development to probe the pharmacology and therapeutic potential of discrete molecular targets, as well as new medicines. In this Perspective, in commemoration of the 2013 Philip S. Portoghese Medicinal Chemistry Lectureship (LindsleyC. W.Adventures in allosteric drug discovery. Presented at the 246th National Meeting of the American Chemical Society, Indianapolis, IN, September 10, 2013; The 2013 Portoghese Lectureship), several vignettes of drug discovery campaigns targeting novel allosteric mechanisms will be recounted, along with lessons learned and guidelines that have emerged for successful lead optimization. PMID:25180768

  13. “What Is Our Story?” Philip Morris’s Changing Corporate Narrative

    Science.gov (United States)

    Malone, Ruth E.

    2015-01-01

    Objectives. We sought to learn how employees reacted to changes in the corporate narrative of Philip Morris Companies (PMC) in the late 1990s and early 2000s. Methods. We analyzed archival internal tobacco industry documents about PMC’s creation of a new corporate story. Results. In response to litigation and public opprobrium, PMC replaced its market success–oriented corporate narrative with a new one centered on responsibility. Although management sought to downplay inconsistencies between the old and new narratives, some employees reportedly had difficulty reconciling them, concerned that the responsibility focus might affect company profitability. However, others embraced the new narrative, suggesting radical ideas to prevent youth smoking. These ideas were not adopted. Conclusions. PMC’s new narrative was unconvincing to many of its employees, who perceived it either as a threat to the company’s continued profits or as incongruous with what they had previously been told. As it had done with the public, PMC misled its employees in explaining a narrative repositioning that would help the company continue business as usual. Moving toward a tobacco endgame will require ongoing discursive and symbolic efforts to disrupt this narrative. PMID:26270280

  14. Conformational changes in the AAA ATPase p97–p47 adaptor complex

    Science.gov (United States)

    Beuron, Fabienne; Dreveny, Ingrid; Yuan, Xuemei; Pye, Valerie E; Mckeown, Ciaran; Briggs, Louise C; Cliff, Matthew J; Kaneko, Yayoi; Wallis, Russell; Isaacson, Rivka L; Ladbury, John E; Matthews, Steve J; Kondo, Hisao; Zhang, Xiaodong; Freemont, Paul S

    2006-01-01

    The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes. PMID:16601695

  15. Portræt: Den sidste aristokrat

    DEFF Research Database (Denmark)

    Henriksen, Carsten

    2009-01-01

    Verdslig vækkelse af hin enkelte. En finurlig og undvigende ironi. En lærer, der ikke ser ned på sine studerende, mens de til gengæld ser op til ham. Det er grundpillerne i Hans Hauges pædagogiske filosofi - set i bakspejlet.......Verdslig vækkelse af hin enkelte. En finurlig og undvigende ironi. En lærer, der ikke ser ned på sine studerende, mens de til gengæld ser op til ham. Det er grundpillerne i Hans Hauges pædagogiske filosofi - set i bakspejlet....

  16. Fast and slow neutrons in an 18-MV photon beam from a Philips SL/75-20 linear accelerator

    International Nuclear Information System (INIS)

    Gur, D.; Rosen, J.C.; Bukovitz, A.G.; Gill, A.W.

    1978-01-01

    Fast- and slow-neutron contamination in an 18-MV photon beam from a Philips SL/75-20 linear accelerator has been measured. Aluminum and indium foils were activated to determine fast- and slow-neutron fluence, which were largely independent of field sizes. Measured fast-neutron fluences were typically 13.9 x 10 4 and 4.4 x 10 4 neutrons/cm 2 /rad of x ray inside and 5 cm outside the field, respectively. Slow-neutron fluences, 1.3 x 10 4 neutrons/cm 2 /rad of x ray, remained relatively constant inside and outside the field. The reported results are about three times higher than neutron fluences recently reported with a betatron operated at the same energy

  17. Quantum corrections to ward identities of chronological AVV- and AAA-current correlators for nondegenerate many-fermion systems in the four-dimensional world

    International Nuclear Information System (INIS)

    Kucheryavij, V.Yi.

    1994-01-01

    The explicit form of nontrivial quantum corrections to Ward identities for AVV- and AAA-current correlators in the four-dimensional world for nondegenerate many-fermion systems of general type is obtained. The characteristics of all nontrivial quantum corrections for nondegenerate two-flavour fermion systems are classified and described. In particular, the well-known results follow from ours for the trivial quantum corrections (anomalies) in the case of the degenerate spectrum of fermion masses

  18. Philip Meyer, o outsider que criou o Jornalismo de Precisão

    Directory of Open Access Journals (Sweden)

    Marília Gehrke

    2017-05-01

    Full Text Available A importância da trajetória de Philip Meyer para os estudos de jornalismo é o ponto principal desta entrevista. Ele é o criador do Jornalismo de Precisão, conceito que aproxima o jornalismo da ciência por meio de métodos científicos sociais, e que, também, dá nome a um de seus livros, publicado pela primeira vez em 1973. Ainda que o Jornalismo de Precisão não demande, necessariamente, o uso de computadores, Meyer começou a trabalhar com as máquinas antes de sua popularização, nos protestos de Detroit, em 1967, depois de passar nove meses na Universidade de Harvard. Utilizando amostra na narrativa jornalística, Meyer e a equipe do jornal Detroit Free Press receberam um Prêmio Pulitzer um ano depois. O Jornalismo de Precisão ainda é um conceito utilizado, mas hoje mais associado ao jornalismo de dados. Nessa entrevista, respondida por email, Meyer não só relembra aspectos de sua carreira e fala sobre a prática jornalística, como o uso de dados, transparência e hipótese, bem como revela suas percepções sobre o futuro do jornalismo.

  19. O PROJETO NATURALISTA DE DAVID HUME À LUZ DA EPISTEMOLOGIA CONTEMPORÂNEA: WILLARD QUINE E PHILIP KITCHER

    Directory of Open Access Journals (Sweden)

    Claudiney José de Sousa

    2017-06-01

    Full Text Available A partir de comparações entre a epistemologia de Hume e os trabalhos de naturalistas contemporâneos, como Willard O. Quine e Philip Kitcher, procuraremos destacar, neste artigo, em que sentido seria possível identificar a revolução epistemológica empreendida por Hume, em seu estudo da natureza humana, como uma espécie de naturalismo, que anteciparia as discussões recentes do tema. A partir dessas discussões, acreditamos poder apresentar mais claramente a sugestão de que, embora Hume não defenda explicitamente este modo de conceber a empresa filosófica, seu projeto filosófico pode, em alguma medida, ser encarado como um programa naturalista, que antecede e inspira o que hoje conhecemos como naturalismo epistemológico.

  20. Comparative study of reconstruction filters for cranio examinations of the Philips system and its influence on the quality of the tomographic image; Estudo comparativo dos filtros de reconstrucao para exames de cranio do sistema Philips e sua influencia na qualidade da imagem tomografica

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, V.C.; Kodlulovich, S.; Delduck, R.S., E-mail: simone@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Oliveira, L.C.G. [Universidade Federal do Rio de Janeiro (CT/UFRJ), RJ (Brazil). Centro de Tecnologia

    2011-07-01

    The aim of this study was to evaluate different reconstruction algorithm (kernels) applied for head examinations. The research was carried out using 40-slice MDCT (Philips, Brilliance 40 CT scanner) and an ACR Phantoms to evaluate the image quality. The doses were estimated applying the coefficients obtained by IMPACT .The study showed that independently of the filter used the values of CT number have no change. The low contrast showed that the choice of correct filter might result a decrease of 9% of doses values. For special resolution, the sharp filter showed a better response for low m As. The noise value of image to certain filters smooth has no changed, even by reducing the m As values. (author)

  1. Comparison of build-up region doses in oblique tangential 6 MV photon beams calculated by AAA and CCC algorithms in breast Rando phantom

    Science.gov (United States)

    Masunun, P.; Tangboonduangjit, P.; Dumrongkijudom, N.

    2016-03-01

    The purpose of this study is to compare the build-up region doses on breast Rando phantom surface with the bolus covered, the doses in breast Rando phantom and also the doses in a lung that is the heterogeneous region by two algorithms. The AAA in Eclipse TPS and the collapsed cone convolution algorithm in Pinnacle treatment planning system were used to plan in tangential field technique with 6 MV photon beam at 200 cGy total doses in Breast Rando phantom with bolus covered (5 mm and 10 mm). TLDs were calibrated with Cobalt-60 and used to measure the doses in irradiation process. The results in treatment planning show that the doses in build-up region and the doses in breast phantom were closely matched in both algorithms which are less than 2% differences. However, overestimate of doses in a lung (L2) were found in AAA with 13.78% and 6.06% differences at 5 mm and 10 mm bolus thickness, respectively when compared with CCC algorithm. The TLD measurements show the underestimate in buildup region and in breast phantom but the doses in a lung (L2) were overestimated when compared with the doses in the two plannings at both thicknesses of the bolus.

  2. Performance characteristics of 3D GSO PET/CT scanner (Philips GEMINI PET/CT)

    International Nuclear Information System (INIS)

    Kim, Jin Su; Lee, Jae Sung; Lee, Byeong Il; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul

    2004-01-01

    Philips GEMINI is a newly introduced whole-body GSO PET/CT scanner. In this study, performance of the scanner including spatial resolution, sensitivity, scatter fraction, noise equivalent count ratio (NECR) was measured utilizing NEMA NU2-2001 standard protocol and compared with performance of LSO, BGO crystal scanner. GEMINI is composed of the Philips ALLEGRO PET and MX8000 D multi-slice CT scanners. The PET scanner has 28 detector segments which have an array of 29 by 22 GSO crystals (4*6*20 mm), covering axial FOV of 18 cm. PET data to measure spatial resolution, sensitivity, scatter fraction, and NECR were acquired in 3D mode according to the NEMA NU2 protocols (coincidence window: 8 ns, energy window : 409∼664 keV). For the measurement of spatial resolution, images were reconstructed with FBP using ramp filter and an iterative reconstruction algorithm, 3D RAMLA. Data for sensitivity measurement were acquired using NEMA sensitivity phantom filled with F-18 solution and surrounded by 1∼5 aluminum sleeves after we confirmed that dead time loss did not exceed 1%. To measure NECR and scatter fraction, 1110 MBq of F-18 solution was injected into a NEMA scatter phantom with a length of 70 cm and dynamic scan with 20-min frame duration was acquired for 7 half-lives. Oblique sinograms were collapsed into transaxial slices using single slice rebinning method, and true to background (scatter + random) ratio for each slice and frame was estimated. Scatter fraction was determined by averaging the true to background ratio of last 3 frames in which the dead time loss was below 1%. Transverse and axial resolutions at 1 cm radius were (1) 5.3 and 6.5 mm (FBP), (2) 5.1 and 5.9 mm (3D RAMLA). Transverse radial, transverse tangential, and axial resolution at 10 cm were (1) 5.7, 5.7, and 7.0 mm (FBP), (2) 5.4, 5.4, and 6.4 mm (3D RAMLA). Attenuation free values of sensitivity were 3,620 counts/sec/MBq at the center of transaxial FOV and 4,324 counts/sec/MBq at 10 cm offset

  3. Geometrical determinations of IMRT photon pencil-beam path in radiotherapy wedges and limit divergence angle with the Anisotropic Analytic Algorithm (AAA

    Directory of Open Access Journals (Sweden)

    Francisco Casesnoves

    2014-08-01

    Full Text Available Purpose: Static wedge filters (WF are commonly used in radiation therapy, forward and/or inverse planning. We calculated the exact 2D/3D geometrical pathway of the photon-beam through the usual alloy WF, in order to get a better dose related to the beam intensity attenuation factor(s, after the beam has passed through the WF. The objective was to provide general formulation into the Anisotropic Analytical Algorithm (AAA model coordinates system (depending on collimator/wedge angles that also can be applied to other models. Additionally, second purpose of this study was to develop integral formulation for 3D wedge exponential factor with statistical approximations, with introduction for the limit angle/conformal wedge.Methods: The radiotherapy model used to develop this mathematical task is the classical superposition-convolution algorithm, AAA (developed by Ulmer and Harder. We worked with optimal geometrical approximations to make the computational IMRT calculations quicker/reduce the planning-system time. Analytic geometry/computational-techniques to carry out simulations (for standard wedges are detailed/developed sharply. Integral developments/integral-statistical approximations are explained. Beam-divergence limit Angle for optimal wedge filtration formulas is calculated/sketched, with geometrical approximations. Fundamental trigonometry is used for this purpose.Results: Extent simulation tables for WF of 15º, 30º, 45º, and 60º are shown with errors. As a result, it is possible to determine the best individual treatment dose distribution for each patient. We presented these basic simulations/numerical examples for standard manufacturing WF of straight sloping surface, to check the accuracy/errors of the calculations. Simulations results give low RMS/Relative Error values (formulated for WF of 15º, 30º, 45º, and 60º.Conclusion: We obtained a series of formulas of analytic geometry for WF that can be applied for any particular dose

  4. SU-F-T-94: Plan2pdf - a Software Tool for Automatic Plan Report for Philips Pinnacle TPS

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C [Sutter Medical Foundation, Roseville, CA (United States)

    2016-06-15

    Purpose: To implement an automatic electronic PDF plan reporting tool for Philips Pinnacle treatment planning system (TPS) Methods: An electronic treatment plan reporting software is developed by us to enable fully automatic PDF report from Pinnacle TPS to external EMR programs such as MOSAIQ. The tool is named “plan2pdf”. plan2pdf is implemented using Pinnacle scripts, Java and UNIX shell scripts, without any external program needed. plan2pdf supports full auto-mode and manual mode reporting. In full auto-mode, with a single mouse click, plan2pdf will generate a detailed Pinnacle plan report in PDF format, which includes customizable cover page, Pinnacle plan summary, orthogonal views through each plan POI and maximum dose point, DRR for each beam, serial transverse views captured throughout the dose grid at a user specified interval, DVH and scorecard windows. The final PDF report is also automatically bookmarked for each section above for convenient plan review. The final PDF report can either be saved on a user specified folder on Pinnacle, or it can be automatically exported to an EMR import folder via a user configured FTP service. In manual capture mode, plan2pdf allows users to capture any Pinnacle plan by full screen, individual window or rectangular ROI drawn on screen. Furthermore, to avoid possible patients’ plan mix-up during auto-mode reporting, a user conflict check feature is included in plan2pdf: it prompts user to wait if another patient is being exported by plan2pdf by another user. Results: plan2pdf is tested extensively and successfully at our institution consists of 5 centers, 15 dosimetrists and 10 physicists, running Pinnacle version 9.10 on Enterprise servers. Conclusion: plan2pdf provides a highly efficient, user friendly and clinical proven platform for all Philips Pinnacle users, to generate a detailed plan report in PDF format for external EMR systems.

  5. SU-F-T-94: Plan2pdf - a Software Tool for Automatic Plan Report for Philips Pinnacle TPS

    International Nuclear Information System (INIS)

    Wu, C

    2016-01-01

    Purpose: To implement an automatic electronic PDF plan reporting tool for Philips Pinnacle treatment planning system (TPS) Methods: An electronic treatment plan reporting software is developed by us to enable fully automatic PDF report from Pinnacle TPS to external EMR programs such as MOSAIQ. The tool is named “plan2pdf”. plan2pdf is implemented using Pinnacle scripts, Java and UNIX shell scripts, without any external program needed. plan2pdf supports full auto-mode and manual mode reporting. In full auto-mode, with a single mouse click, plan2pdf will generate a detailed Pinnacle plan report in PDF format, which includes customizable cover page, Pinnacle plan summary, orthogonal views through each plan POI and maximum dose point, DRR for each beam, serial transverse views captured throughout the dose grid at a user specified interval, DVH and scorecard windows. The final PDF report is also automatically bookmarked for each section above for convenient plan review. The final PDF report can either be saved on a user specified folder on Pinnacle, or it can be automatically exported to an EMR import folder via a user configured FTP service. In manual capture mode, plan2pdf allows users to capture any Pinnacle plan by full screen, individual window or rectangular ROI drawn on screen. Furthermore, to avoid possible patients’ plan mix-up during auto-mode reporting, a user conflict check feature is included in plan2pdf: it prompts user to wait if another patient is being exported by plan2pdf by another user. Results: plan2pdf is tested extensively and successfully at our institution consists of 5 centers, 15 dosimetrists and 10 physicists, running Pinnacle version 9.10 on Enterprise servers. Conclusion: plan2pdf provides a highly efficient, user friendly and clinical proven platform for all Philips Pinnacle users, to generate a detailed plan report in PDF format for external EMR systems.

  6. Philip McLaren and the Indigenous-Australian Crime Novel

    Directory of Open Access Journals (Sweden)

    Cornelis Martin Renes

    2017-01-01

    Full Text Available This paper locates the postcolonial crime novel as a space for disenfranchised groups to write back to the marginalisation inherent in the process of colonisation, and explores the example of Australia. From its inception in the mid-19th century, Australian crime fiction reflected upon the challenging harshness and otherness of the Australian experience for the free and convict settler, expelled from the metropole. It created a series of popular subgenres derived from the convict narrative proper, while more ‘standard’ modes of crime fiction, popularised in and through British and American crime fiction, were late to develop. Whereas Australian crime fiction has given expression to the white experience of the continent in manifold ways, up until recently it made no room for Indigenous voices – with the exception of the classic Inspector Napoleon Bonaparte series written by the prolific Arthur Upfield in the first half of the 20th century. For the longest time, this absence reflected the dispossession, dispersal and disenfranchisement of the colonised Indigenous peoples at large; there were neither Aboriginal voices nor Aboriginal authors, which made the textual space of the Australian crime novel a discursive terra nullius. This paper will look at the only Indigenous-Australian author to date with a substantial body of work in crime fiction, Philip McLaren, and elucidate how his four crime novels break new ground in Australian crime fiction by embedding themselves within a political framework of Aboriginal resilience and resistance to neo/colonialism. Written as of the 1990s, McLaren’s oeuvre is eclectic in that it does not respond to traditional formats of Australian crime fiction, shifts between generic subtypes and makes incursions into other genres. The paper concludes that McLaren’s oeuvre has not been conceived of as the work of a crime writer per se, but rather that its form and content are deeply informed by the racist violence

  7. Agrobacterium tumefaciens-mediated genetic transformation of embryogenesis cell suspensions of banana cultivar Grande naine (AAA

    Directory of Open Access Journals (Sweden)

    Idalmis Bermúdez-Caraballoso

    2004-01-01

    Full Text Available The black Sigatoka (Mycosphaerella fijiensis Morelet has become in the last years, the most destructive disease that affects the production of banana and plantains world-wide. The present work was made with the objective to obtain transgenic plants of banana cultivar Grand naine (AAA resistant to this disease with the use of genetic transformation. Embryogenenic cell suspensions obtained from somatic embryos formed from immature male flowers, were used for the transformation by Agrobacterium tumefaciens. The bacterial strain EHA-105 was used with the binary plasmids pHCA-58, pHCG-59 and pHGA-91, which contain different combinations of genes that encode for the antifungal chitinase, glucanase enzymes and the AP-24 osmotin. The commercial herbicide BASTA® was used as selective agent. One hundred ten putative transformed lines of the three constructions were obtained, after three selection months in the culture medium. The transgenic events were verified by means of Polymerase Chain Reaction analysis. Key words: AP-24, chitinase, glucanase, Musa, Mycosphaerella fijiensis

  8. In vitro propagation and assessment of the genetic fidelity of Musa acuminata (AAA) cv. Vaibalhla derived from immature male flowers.

    Science.gov (United States)

    Hrahsel, Lalremsiami; Basu, Adreeja; Sahoo, Lingaraj; Thangjam, Robert

    2014-02-01

    An efficient in vitro propagation method has been developed for the first time for Musa acuminata (AAA) cv. Vaibalhla, an economically important banana cultivar of Mizoram, India. Immature male flowers were used as explants. Murashige and Skoog's (MS) medium supplemented with plant growth regulators (PGRs) were used for the regeneration process. Out of different PGR combinations, MS medium supplemented with 2 mg L(-1) 6-benzylaminopurine (BAP) + 0.5 mg L(-1) α-naphthalene acetic acid (NAA) was optimal for production of white bud-like structures (WBLS). On this medium, explants produced the highest number of buds per explant (4.30). The highest percentage (77.77) and number (3.51) of shoot formation from each explants was observed in MS medium supplemented with 2 mg L(-1) kinetin + 0.5 mg L(-1) NAA. While MS medium supplemented with a combination of 2 mg L(-1) BAP + 0.5 mg L(-1) NAA showed the maximum shoot length (14.44 cm). Rooting efficiency of the shoots was highest in the MS basal medium without any PGRs. The plantlets were hardened successfully in the greenhouse with 96% survival rate. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were employed to assess the genetic stability of in vitro regenerated plantlets of M. acuminata (AAA) cv. Vaibalhla. Eight RAPD and 8 ISSR primers were successfully used for the analysis from the 40 RAPD and 30 ISSR primers screened initially. The amplified products were monomorphic across all the regenerated plants and were similar to the mother plant. The present standardised protocol will find application in mass production, conservation and genetic transformation studies of this commercially important banana.

  9. Caracterização do grânulo de amido de bananas (Musa AAA-Nanicão e Musa AAB-Terra)

    OpenAIRE

    Freitas,M.C.J.; Tavares,D.de Q.

    2005-01-01

    O amido de bananas tem sido pesquisado na área de nutrição a partir da introdução do conceito de Amido Resistente. O amido de Musa AAA-Nanicão e Musa AAB-Terra foram caracterizados quanto as suas respostas fisiológicas [12]. Em continuidade, o presente trabalho estudou características físicas e morfológicas dos grânulos de amido de ambas as espécies de banana comparando-as com amido nativo de milho comercial. O amido de bananas foi extraído segundo CHIANG, CHU & CHU [3]. A morfologia dos ...

  10. Clinical trial registries: a practical guide for sponsors and researchers of medicinal products

    National Research Council Canada - National Science Library

    Foote, MaryAnn

    2006-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix MaryAnn Foote Clinical trial registries and publication of results - a primer . . . . . . . . . . . . . . . . . . 1 Ana Marušić and Charlotte Haug The journal...

  11. Fiscal versus social responsibility: how Philip Morris shaped the public funds divestment debate

    Science.gov (United States)

    Wander, N; Malone, R E

    2006-01-01

    Calls for institutional investors to divest (sell off) tobacco stocks threaten the industry's share values, publicise its bad behaviour, and label it as a politically unacceptable ally. US tobacco control advocates began urging government investment and pension funds to divest as a matter of responsible social policy in 1990. Following the initiation of Medicaid recovery lawsuits in 1994, advocates highlighted the contradictions between state justice departments suing the industry, and state health departments expanding tobacco control programmes, while state treasurers invested in tobacco companies. Philip Morris (PM), the most exposed US company, led the divestment opposition, consistently framing the issue as one of responsible fiscal policy. It insisted that funds had to be managed for the exclusive interest of beneficiaries, not the public at large, and for high share returns above all. This paper uses tobacco industry documents to show how PM sought to frame both the rhetorical contents and the legal contexts of the divestment debate. While tobacco stock divestment was eventually limited to only seven (but highly visible) states, US advocates focused public attention on the issue in at least 18 others plus various local jurisdictions. This added to ongoing, effective campaigns to denormalise and delegitimise the tobacco industry, dividing it from key allies. Divestment as a delegitimisation tool could have both advantages and disadvantages as a tobacco control strategy in other countries. PMID:16728755

  12. Corporate Image and Public Health: An Analysis of the Philip Morris, Kraft, and Nestlé Websites

    Science.gov (United States)

    SMITH, ELIZABETH

    2012-01-01

    Companies need to maintain a good reputation to do business; however, companies in the infant formula, tobacco, and processed food industries have been identified as promoting disease. Such companies use their websites as a means of promulgating a positive public image, thereby potentially reducing the effectiveness of public health campaigns against the problems they perpetuate. The author examined documents from the websites of Philip Morris, Kraft, and Nestlé for issue framing and analyzed them using Benoit’s typology of corporate image repair strategies. All three companies defined the problems they were addressing strategically, minimizing their own responsibility and the consequences of their actions. They proposed solutions that were actions to be taken by others. They also associated themselves with public health organizations. Health advocates should recognize industry attempts to use relationships with health organizations as strategic image repair and reject industry efforts to position themselves as stakeholders in public health problems. Denormalizing industries that are disease vectors, not just their products, may be critical in realizing positive change. PMID:22420639

  13. System upgrade on Philips Allura FD20 angiography systems: effects on patient skin dose and static image quality

    International Nuclear Information System (INIS)

    Ryckx, Nick; Sans-Merce, Marta; Meuli, Reto; Zerlauth, Jean-Baptiste; Verdun, Francis R.

    2016-01-01

    Fluoroscopically guided procedures might be highly irradiating for patients, possibly leading to skin injuries. In such a context, every effort should be done to lower patient exposure as much as possible. Moreover, patient dose reduction does not only benefit to the patient but also allows reducing staff exposure. In this framework, Philips Healthcare recently introduced a system upgrade for their angiography units, called 'AlluraClarity'. The authors performed air kerma rate measurements for all available fluoroscopy modes and air kerma per frame measurements for the digital subtraction angiography protocols, along with subjective spatial resolution and low-contrast detectability assessments using a standard QA phantom. Air kerma reductions ranging from 25.5 to 84.4 % were found, with no significant change in image quality when switching from a standard operating mode to an upgraded version. These results are confirmed by the comparison of actual patient exposures for similar procedures. (authors)

  14. Comparison of different tube-of-response (TOR) models for resolution recovery in PET image reconstruction for the Philips Ingenuity TF PET/MR

    International Nuclear Information System (INIS)

    Lougovski, Alexandr; Hofheinz, Frank; Van Den Hoff, Jorg

    2015-01-01

    Recently, we have proposed a method for on-the-fly system matrix computation where the tube-of-response (TOR) is approximated as a cylinder with constant density (TORCD) and the cubic voxels are replaced by spheres. We could show that with this model the PET image quality can be notably improved compared to the vendor provided image reconstruction of our Philips Ingenuity-TF PET/MR. In this work we address the question whether image quality can be further improved by using a variable density TOR (TOR-VD). The radial variability of TOR-VD was modelled by a Kaiser-Bessel function. Free parameters of this density model were used to optimize image properties regarding resolution, noise, and Gibbs artifacts. Additional, a TOR-VD model accounting for position dependent effects along the TOR caused by the finite solid angles of the detectors is under investigation. Phantom measurement were performed with a Philips Ingenuity-TF PET/MR scanner. Listmode data were reconstructed using TOR-CD and TORVD, respectively on two different grids with cubic voxel size of 2 mm and 4 mm. Image quality was assessed with resolution-noise curves and investigation of the radial position dependence of the spatial resolution. For 2 mm voxels, TOR-VD consistently yields a slight improvement of the investigated image quality measures compared to TOR-CD. For 4 mm voxels both models lead essentially to the same results. These findings can be understood as a consequence of the relative size of voxel and TOR. For typical whole body studies (4 mm voxel size) a variable TOR does not improve image quality beyond what is achievable with a constant density TOR. For smaller voxel size the image quality can indeed be somewhat improved with a variable TOR but at the expense of drastically increased computation time.

  15. Comparison of different tube-of-response (TOR) models for resolution recovery in PET image reconstruction for the Philips Ingenuity TF PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Lougovski, Alexandr; Hofheinz, Frank; Van Den Hoff, Jorg [Helmholtz-Center Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center, Dresden (Germany)

    2015-05-18

    Recently, we have proposed a method for on-the-fly system matrix computation where the tube-of-response (TOR) is approximated as a cylinder with constant density (TORCD) and the cubic voxels are replaced by spheres. We could show that with this model the PET image quality can be notably improved compared to the vendor provided image reconstruction of our Philips Ingenuity-TF PET/MR. In this work we address the question whether image quality can be further improved by using a variable density TOR (TOR-VD). The radial variability of TOR-VD was modelled by a Kaiser-Bessel function. Free parameters of this density model were used to optimize image properties regarding resolution, noise, and Gibbs artifacts. Additional, a TOR-VD model accounting for position dependent effects along the TOR caused by the finite solid angles of the detectors is under investigation. Phantom measurement were performed with a Philips Ingenuity-TF PET/MR scanner. Listmode data were reconstructed using TOR-CD and TORVD, respectively on two different grids with cubic voxel size of 2 mm and 4 mm. Image quality was assessed with resolution-noise curves and investigation of the radial position dependence of the spatial resolution. For 2 mm voxels, TOR-VD consistently yields a slight improvement of the investigated image quality measures compared to TOR-CD. For 4 mm voxels both models lead essentially to the same results. These findings can be understood as a consequence of the relative size of voxel and TOR. For typical whole body studies (4 mm voxel size) a variable TOR does not improve image quality beyond what is achievable with a constant density TOR. For smaller voxel size the image quality can indeed be somewhat improved with a variable TOR but at the expense of drastically increased computation time.

  16. Apropiación y alienación: consideraciones hermenéutico-existenciales a propósito de la Pastoral americana de Philip Roth

    Directory of Open Access Journals (Sweden)

    Germán Darío Vélez López

    2013-01-01

    Full Text Available Partiendo de una formulación básica de algunos elementos relevantes de la hermenéutica fenomenológica de Heidegger, el presente artículo propone una lectura de la obra del escritor norteamericano Philip Roth titulada Pastoral americana, que lo hizo acreedor al premio Pulitzer en 1989. El propósito cen- tral de esa lectura consiste en mostrar de qué manera fenómenos existenciales elementales como estar-lejos (Wegsein, estar-despierto (Wachsein, estar-ahí (Dasein permiten una articulación propia del sentido de la obra de Roth en la que ésta manifiesta su particular compromiso existencial.

  17. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan; Rosenberg, Scott C.; Hagemann, Goetz; Herzog, Franz; Tóth, Attila; Cleveland, Don W.; Corbett, Kevin D.

    2017-06-28

    Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “pore loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.

  18. Interaction studies of resistomycin from Streptomyces aurantiacus AAA5 with calf thymus DNA and bovine serum albumin

    Science.gov (United States)

    Vijayabharathi, R.; Sathyadevi, P.; Krishnamoorthy, P.; Senthilraja, D.; Brunthadevi, P.; Sathyabama, S.; Priyadarisini, V. Brindha

    2012-04-01

    Resistomycin, a secondary metabolite produced by Streptomyces aurantiacus AAA5. The binding interaction of resistomycin with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was investigated by spectrophotometry, spectrofluorimetry, circular dichroism (CD) and synchronous fluorescence techniques under physiological conditions in vitro. Absorption spectral studies along with the fluorescence competition with ethidium bromide measurements and circular dichroism clearly suggest that the resistomycin bind with CT DNA relatively strong via groove binding. BSA interaction results revealed that the drug was found to quench the fluorescence intensity of the protein through a static quenching mechanism. The number of binding sites 'n' and apparent binding constant 'K' calculated according to the Scatchard equation exhibit a good binding property to bovine serum albumin protein. In addition, the results observed from synchronous fluorescence measurements clearly demonstrate the occurrence of conformational changes of BSA upon addition of the test compound.

  19. Comparative study of reconstruction filters for cranio examinations of the Philips system and its influence on the quality of the tomographic image

    International Nuclear Information System (INIS)

    Silveira, V.C.; Kodlulovich, S.; Delduck, R.S.; Oliveira, L.C.G.

    2011-01-01

    The aim of this study was to evaluate different reconstruction algorithm (kernels) applied for head examinations. The research was carried out using 40-slice MDCT (Philips, Brilliance 40 CT scanner) and an ACR Phantoms to evaluate the image quality. The doses were estimated applying the coefficients obtained by IMPACT .The study showed that independently of the filter used the values of CT number have no change. The low contrast showed that the choice of correct filter might result a decrease of 9% of doses values. For special resolution, the sharp filter showed a better response for low m As. The noise value of image to certain filters smooth has no changed, even by reducing the m As values. (author)

  20. Interpreting the Dæmonomicon: A Decade of Teaching Philip Pullman’s Northern Lights

    Directory of Open Access Journals (Sweden)

    Jessica Allen Hanssen

    2018-05-01

    Full Text Available Philip Pullman’s His Dark Materials trilogy reinvigorated the high fantasy genre, not least by his invention of the dæmon. In this article I argue that the dæmon concept, when applied as a drawing exercise in the teacher education context, provides important insight into the vast diversity of interests, feelings, and values of ELT student teachers as they prepare to enter their chosen profession. From the years 2007-2017, approximately 200 university students were invited to draw a representation of their ‘dæmon’. The drawings, assembled and analysed as a data set based on markers such as the student teachers’ gender, as well as by content, size, and relative creativity, allow certain patterns and tendencies to become visible, and individual drawings also serve as important reflection points on the novel and the nature of teaching literature. Northern Lights, the first book of His Dark Materials trilogy, makes for excellent reading, and is also a helpful book to use in the teacher education context, to help student teachers learn the conventions of the fantasy genre and understand how knowledge of the genre can enhance their teaching practice. This article therefore presents a long-term learning activity connected to teaching Northern Lights, as a way into working with genre conventions, and also as a point of departure on the subject of the importance of self-reflection in the literature classroom’s interpretative community.

  1. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

    Science.gov (United States)

    Martinelli, Paola; Cherukuri, Praveen F.; Teer, Jamie K.; Hansen, Nancy F.; Cruz, Pedro; Mullikin for the NISC Comparative Sequencing Program, James C.; Blakesley, Robert W.; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I.; Langer, Thomas; Gahl, William A.; Toro, Camilo

    2011-01-01

    We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284

  2. Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases.

    Directory of Open Access Journals (Sweden)

    Tyler Mark Pierson

    2011-10-01

    Full Text Available We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7. Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28, a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial" features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.

  3. SU-E-T-596: P3DVHStats - a Novel, Automatic, Institution Customizable Program to Compute and Report DVH Quantities On Philips Pinnacle TPS

    International Nuclear Information System (INIS)

    Wu, C

    2015-01-01

    Purpose: To implement a novel, automatic, institutional customizable DVH quantities evaluation and PDF report tool on Philips Pinnacle treatment planning system (TPS) Methods: An add-on program (P3DVHStats) is developed by us to enable automatic DVH quantities evaluation (including both volume and dose based quantities, such as V98, V100, D2), and automatic PDF format report generation, for EMR convenience. The implementation is based on a combination of Philips Pinnacle scripting tool and Java language pre-installed on each Pinnacle Sun Solaris workstation. A single Pinnacle script provide user a convenient access to the program when needed. The activated script will first export DVH data for user selected ROIs from current Pinnacle plan trial; a Java program then provides a simple GUI interface, utilizes the data to compute any user requested DVH quantities, compare with preset institutional DVH planning goals; if accepted by users, the program will also generate a PDF report of the results and export it from Pinnacle to EMR import folder via FTP. Results: The program was tested thoroughly and has been released for clinical use at our institution (Pinnacle Enterprise server with both thin clients and P3PC access), for all dosimetry and physics staff, with excellent feedback. It used to take a few minutes to use MS-Excel worksheet to calculate these DVH quantities for IMRT/VMAT plans, and manually save them as PDF report; with the new program, it literally takes a few mouse clicks in less than 30 seconds to complete the same tasks. Conclusion: A Pinnacle scripting and Java language based program is successfully implemented, customized to our institutional needs. It is shown to dramatically reduce time and effort needed for DVH quantities computing and EMR reporting

  4. SU-E-T-596: P3DVHStats - a Novel, Automatic, Institution Customizable Program to Compute and Report DVH Quantities On Philips Pinnacle TPS

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C [Sutter Medical Foundation, Roseville, CA (United States)

    2015-06-15

    Purpose: To implement a novel, automatic, institutional customizable DVH quantities evaluation and PDF report tool on Philips Pinnacle treatment planning system (TPS) Methods: An add-on program (P3DVHStats) is developed by us to enable automatic DVH quantities evaluation (including both volume and dose based quantities, such as V98, V100, D2), and automatic PDF format report generation, for EMR convenience. The implementation is based on a combination of Philips Pinnacle scripting tool and Java language pre-installed on each Pinnacle Sun Solaris workstation. A single Pinnacle script provide user a convenient access to the program when needed. The activated script will first export DVH data for user selected ROIs from current Pinnacle plan trial; a Java program then provides a simple GUI interface, utilizes the data to compute any user requested DVH quantities, compare with preset institutional DVH planning goals; if accepted by users, the program will also generate a PDF report of the results and export it from Pinnacle to EMR import folder via FTP. Results: The program was tested thoroughly and has been released for clinical use at our institution (Pinnacle Enterprise server with both thin clients and P3PC access), for all dosimetry and physics staff, with excellent feedback. It used to take a few minutes to use MS-Excel worksheet to calculate these DVH quantities for IMRT/VMAT plans, and manually save them as PDF report; with the new program, it literally takes a few mouse clicks in less than 30 seconds to complete the same tasks. Conclusion: A Pinnacle scripting and Java language based program is successfully implemented, customized to our institutional needs. It is shown to dramatically reduce time and effort needed for DVH quantities computing and EMR reporting.

  5. Obituary: Philip Morrison, 1915-2005

    Science.gov (United States)

    Trimble, Virginia

    2005-12-01

    Philip Morrison, who died 22 April 2005 in Cambridge, Massachusetts, was born in Somerville, New Jersey on 7 November 1915 to Moses and Tilly (née Rosenbloom) Morrison. Early childhood polio confined him for extended periods, during which he apparently developed his remarkable skill at speed reading. Speed writing (leading to a bibliography of more than 600 items) came later, and his memory must always have been exceedingly retentive. Morrison went on from the public and private schools of Pittsburgh, Pennsylvania to receive a BS in physics from Carnegie Institute of Technology (now Carnegie Mellon) in 1936. At the University of California, Berkeley, he joined the Young Communist League and later the Communist Party, letting his membership lapse in the early 1940s when work and war came to seem more important. He was officially the student of J. Robert Oppenheimer and worked also with postdocs Robert Serber and Leonard Schiff and with a number of his fellow Oppenheimer students (a spectacular crew, which included Robert Christy, Sidney Dancoff, Bernard Peters [born Pietrkowski], Hartland Snyder, Joseph Weinberg, Dale Corson, Giovanni Rossi Lomanitz, David Bohm, and Eugene Cooper). Following his 1940 PhD, Phil (his preferred signature) taught for a year at San Francisco State and then at University of Illinois (where he replaced Dancoff, who had gone on to a year at Institute for Advanced Study, Princeton). From Illinois, Morrison was recruited to the Metallurgy Lab (uranium project) at the University of Chicago by Christy in 1942. There he worked on the design for the Hanford Reactor, the main source of plutonium for the Trinity and Nagasaki bombs. He seems to have been sensitive to human relationships even in that context and was the author of a "Dear Opje" letter to Oppenheimer pointing out that the lack of cooperation between management and the scientists was getting in the way of the project. Morrison's early research was largely in theoretical nuclear physics

  6. Nashemu zdravoohraneniju trebujetsja skoraja pomoshtsh / Boris Tuch

    Index Scriptorium Estoniae

    Tuch, Boris, 1946-

    2002-01-01

    Toimetuse ümarlauas võtavad tervishoiu hetkeprobleemidest sõna psühhiaater, Keskerakonna parlamendisaadik Arvo Haug, Tallinna Läänehaigla hiljutine peaarst Peeter Mardna, professor Natan Elshtein ja farmaatsiafirma Vitale XD direktor Marina Grintshak

  7. Workshop Are you serious? Evidence for Learning using Games

    NARCIS (Netherlands)

    Nadolski, Rob; Baalsrud Hauge, Jannicke; Boyle, Elizabeth; Riedl, Johann; Mayer, Igor; Moreno-Ger, Pablo

    2012-01-01

    Nadolski, R. J., Baalsrud Hauge, J., Boyle, E., Riedl, J., Mayer, I., & Moreno-Ger, P. (2012, 28-30 November). Workshop Are you serious? Evidence for Learning using Games. Workshop at Online Educa Berlin, Berlin, Germany.

  8. The CoxD protein, a novel AAA+ ATPase involved in metal cluster assembly: hydrolysis of nucleotide-triphosphates and oligomerization.

    Directory of Open Access Journals (Sweden)

    Tobias Maisel

    Full Text Available CoxD of the α-proteobacterium Oligotropha carboxidovorans is a membrane protein which is involved in the posttranslational biosynthesis of the [CuSMoO₂] cluster in the active site of the enzyme CO dehydrogenase. The bacteria synthesize CoxD only in the presence of CO. Recombinant CoxD produced in E. coli K38 pGP1-2/pETMW2 appeared in inclusion bodies from where it was solubilized by urea and refolded by stepwise dilution. Circular dichroism spectroscopy revealed the presence of secondary structural elements in refolded CoxD. CoxD is a P-loop ATPase of the AAA-protein family. Refolded CoxD catalyzed the hydrolysis of MgATP yielding MgADP and inorganic phosphate at a 1∶1∶1 molar ratio. The reaction was inhibited by the slow hydrolysable MgATP-γ-S. GTPase activity of CoxD did not exceed 2% of the ATPase activity. Employing different methods (non linear regression, Hanes and Woolf, Lineweaver-Burk, preparations of CoxD revealed a mean K(M value of 0.69±0.14 mM ATP and an apparent V(max value of 19.3±2.3 nmol ATP hydrolyzed min⁻¹ mg⁻¹. Sucrose density gradient centrifugation and gel filtration showed that refolded CoxD can exist in various multimeric states (2-mer, 4-mer or 6-mer, preferentially as hexamer or dimer. Within weeks the hexamer dissociates into the dimer, a process which can be reversed by MgATP or MgATP-γ-S within hours. Only the hexamers and the dimers exhibited MgATPase activity. Transmission electron microscopy of negatively stained CoxD preparations revealed distinct particles within a size range of 10-16 nm, which further corroborates the oligomeric organization. The 3D structure of CoxD was modeled with the 3D structure of BchI from Rhodobacter capsulatus as template. It has the key elements of an AAA+ domain in the same arrangement and at same positions as in BchI and displays the characteristic inserts of the PS-II-insert clade. Possible functions of CoxD in [CuSMoO₂] cluster assembly are discussed.

  9. Võistlused : [kalasport, 28. apr. - 30. juun. 2012

    Index Scriptorium Estoniae

    2012-01-01

    Kevadkalake, Töörahva Kala, Kevadsärg, Vagula Röövik, Saadjärve Haug, EMV Õngitsemises (mehed), Linnakala, Suure-Jaani Spinning, Tuulekala Trolling, Rakvere Koger, Gorodenko Spinning, EMV Õngitsemises (naised ja noored)

  10. SU-F-P-39: End-To-End Validation of a 6 MV High Dose Rate Photon Beam, Configured for Eclipse AAA Algorithm Using Golden Beam Data, for SBRT Treatments Using RapidArc

    Energy Technology Data Exchange (ETDEWEB)

    Ferreyra, M; Salinas Aranda, F; Dodat, D; Sansogne, R; Arbiser, S [Vidt Centro Medico, Ciudad Autonoma De Buenos Aires, Ciudad Autonoma de Buenos Aire (Argentina)

    2016-06-15

    Purpose: To use end-to-end testing to validate a 6 MV high dose rate photon beam, configured for Eclipse AAA algorithm using Golden Beam Data (GBD), for SBRT treatments using RapidArc. Methods: Beam data was configured for Varian Eclipse AAA algorithm using the GBD provided by the vendor. Transverse and diagonals dose profiles, PDDs and output factors down to a field size of 2×2 cm2 were measured on a Varian Trilogy Linac and compared with GBD library using 2% 2mm 1D gamma analysis. The MLC transmission factor and dosimetric leaf gap were determined to characterize the MLC in Eclipse. Mechanical and dosimetric tests were performed combining different gantry rotation speeds, dose rates and leaf speeds to evaluate the delivery system performance according to VMAT accuracy requirements. An end-to-end test was implemented planning several SBRT RapidArc treatments on a CIRS 002LFC IMRT Thorax Phantom. The CT scanner calibration curve was acquired and loaded in Eclipse. PTW 31013 ionization chamber was used with Keithley 35617EBS electrometer for absolute point dose measurements in water and lung equivalent inserts. TPS calculated planar dose distributions were compared to those measured using EPID and MapCheck, as an independent verification method. Results were evaluated with gamma criteria of 2% dose difference and 2mm DTA for 95% of points. Results: GBD set vs. measured data passed 2% 2mm 1D gamma analysis even for small fields. Machine performance tests show results are independent of machine delivery configuration, as expected. Absolute point dosimetry comparison resulted within 4% for the worst case scenario in lung. Over 97% of the points evaluated in dose distributions passed gamma index analysis. Conclusion: Eclipse AAA algorithm configuration of the 6 MV high dose rate photon beam using GBD proved efficient. End-to-end test dose calculation results indicate it can be used clinically for SBRT using RapidArc.

  11. Unique ATPase site architecture triggers cis-mediated synchronized ATP binding in heptameric AAA+-ATPase domain of flagellar regulatory protein FlrC.

    Science.gov (United States)

    Dey, Sanjay; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli

    2015-04-03

    Bacterial enhancer-binding proteins (bEBPs) oligomerize through AAA(+) domains and use ATP hydrolysis-driven energy to isomerize the RNA polymerase-σ(54) complex during transcriptional initiation. Here, we describe the first structure of the central AAA(+) domain of the flagellar regulatory protein FlrC (FlrC(C)), a bEBP that controls flagellar synthesis in Vibrio cholerae. Our results showed that FlrC(C) forms heptamer both in nucleotide (Nt)-free and -bound states without ATP-dependent subunit remodeling. Unlike the bEBPs such as NtrC1 or PspF, a novel cis-mediated "all or none" ATP binding occurs in the heptameric FlrC(C), because constriction at the ATPase site, caused by loop L3 and helix α7, restricts the proximity of the trans-protomer required for Nt binding. A unique "closed to open" movement of Walker A, assisted by trans-acting "Glu switch" Glu-286, facilitates ATP binding and hydrolysis. Fluorescence quenching and ATPase assays on FlrC(C) and mutants revealed that although Arg-349 of sensor II, positioned by trans-acting Glu-286 and Tyr-290, acts as a key residue to bind and hydrolyze ATP, Arg-319 of α7 anchors ribose and controls the rate of ATP hydrolysis by retarding the expulsion of ADP. Heptameric state of FlrC(C) is restored in solution even with the transition state mimicking ADP·AlF3. Structural results and pulldown assays indicated that L3 renders an in-built geometry to L1 and L2 causing σ(54)-FlrC(C) interaction independent of Nt binding. Collectively, our results underscore a novel mechanism of ATP binding and σ(54) interaction that strives to understand the transcriptional mechanism of the bEBPs, which probably interact directly with the RNA polymerase-σ(54) complex without DNA looping. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Chloe Girard

    2015-07-01

    Full Text Available Meiotic crossovers (COs generate genetic diversity and are critical for the correct completion of meiosis in most species. Their occurrence is tightly constrained but the mechanisms underlying this limitation remain poorly understood. Here we identified the conserved AAA-ATPase FIDGETIN-LIKE-1 (FIGL1 as a negative regulator of meiotic CO formation. We show that Arabidopsis FIGL1 limits CO formation genome-wide, that FIGL1 controls dynamics of the two conserved recombinases DMC1 and RAD51 and that FIGL1 hinders the interaction between homologous chromosomes, suggesting that FIGL1 counteracts DMC1/RAD51-mediated inter-homologue strand invasion to limit CO formation. Further, depleting both FIGL1 and the previously identified anti-CO helicase FANCM synergistically increases crossover frequency. Additionally, we showed that the effect of mutating FANCM on recombination is much lower in F1 hybrids contrasting from the phenotype of inbred lines, while figl1 mutation equally increases crossovers in both contexts. This shows that the modes of action of FIGL1 and FANCM are differently affected by genomic contexts. We propose that FIGL1 and FANCM represent two successive barriers to CO formation, one limiting strand invasion, the other disassembling D-loops to promote SDSA, which when both lifted, leads to a large increase of crossovers, without impairing meiotic progression.

  13. Deploying Serious Games for Management in Higher Education: lessons learned and good practices

    NARCIS (Netherlands)

    Baalsrud Hauge, Jannicke; Bellotti, Francesco; Nadolski, Rob; Kickmeier-Rust, Michael; Berta, Riccardo; Carvalho, Maria B.

    2013-01-01

    Baalsrud Hauge, J., Bellotti, F., Nadolski, R. J., Kickmeier-Rust, M., Berta, R., & Carvalho, M. B. (2013, 4 October). Deploying Serious Games for Management in Higher Education: lessons learned and good practices. Presentation at ECGBL 2013, Porto, Portugal.

  14. El liderazgo transformacional de los directivos y las actitudes de los docentes hacia el compromiso organizacional en la Institución Educativa N° 5084 "Carlos Philips Previ" Callao 2010- 2011

    OpenAIRE

    Minaya Canales, Manuel Segundo

    2014-01-01

    Se ha diseñado un estudio descriptivo correlacional con el objetivo de determinar la relación que existe entre el liderazgo transformacional de los directivos y las actitudes de compromiso organizacional de los docentes en la Institución Educativa Nº 5084 “Carlos Philips Previ” Callao. La muestra estuvo constituida por 39 empleados de la Institución Educativa, entre docentes y personal directivo. Para la medición de la variable Liderazgo transformacional se diseñó un instrumento compuesto de ...

  15. Directori ülesanne : Perefirma juhtum / Maret Ahonen

    Index Scriptorium Estoniae

    Ahonen, Maret, 1959-

    2007-01-01

    Probleemidest perefirmas. Lahendusi pakuvad Sideameti peadirektor Ando Rehemaa: Kõigepealt sea pingeritta enda valikud; psühholoog ja koolitaja Sirje Pree: Nagu luik, haug ja vähk; Büroomaailma tegevjuht Jüri Ross: Kainet mõistust ja sooja südant!

  16. The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

    Science.gov (United States)

    Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

    2018-03-01

    In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  17. Gifts reserved for age: a Lacanian study of comedy in Philip Roth’s Exit Ghost = Dons reservados para a idade madura: um estudo lacaniano sobre a comédia em O fantasma sai de cena (2007, de Philip Roth

    Directory of Open Access Journals (Sweden)

    James Milton Mellard

    2010-01-01

    Full Text Available The critical problem surrounding Philip Roth’s recent Exit Ghost (2007, the ninth and projected by the author as the final Zuckerman novel, is how it can function as comedy when one major character is dying of brain cancer and its protagonist is seventy-one years old, beginning to receive an elderly male’s gifts reserved for age –prostate cancer, prostate surgery, impotence, and incontinence – and, despite all, falls in love with a thirty-year-old married woman. A sequel to The Ghost Writer (1979, the first Zuckerman novel, whose character relations it repeats, Exit Ghost has comparatively less humor than its predecessor but there is humor enough. Moreover, and more important, it fits the genre of comedy because of the functions it gives to the classically traditional motifs of the phallus, castration, age versus youth, Eros and Thanatos, and the like. It is from a Lacanian critical perspective that it can be shown how the novel moves toward comedy’s conventional happy ending because of the duality of meanings attached to the matter of castration, the way in which Roth/Zuckerman displaces the object of desire from the young woman and finds it – enjoyment, jouissance – in the very process of writing itself.O grande problema para a crítica de O fantasma sai de cena, até agora o penúltimo romance de Philip Roth, concebido como o último envolvendo Nathan Zuckerman, é classificá-lo como comédia, e um de seus mais importantes personagens está morrendo de câncer no cérebro e o protagonista tem 71 anos e já está recebendo os dons reservados para a idade madura masculina, ou seja, câncer de próstata, cirurgia prostática, impotência, incontinência urinária e, apesar de tudo, apaixona-se por uma mulher casada, de 30 anos. Sendo uma continuação da série iniciada por The Ghost Writer (1979, o primeiro romance em que aparece o personagem Zuckerman, cujas relações com os demaispersonagens se repetem, O fantasma sai de cena

  18. Oil-free piston compressors for compressed air and gas; Oellose Kolbenkompressoren fuer Druckluft und Gase

    Energy Technology Data Exchange (ETDEWEB)

    Frefel, B. [Fritz Haug AG, St. Gallen (Switzerland)

    2002-11-01

    Oil-free compressors are lubricated with special materials in dry operation. The technology was developed 35 years ago by the Swiss company, Fritz Haug AG. Originally developed for 10 - 40 bar, oil-free compressors are now available for both the low-pressure and high-pressure range. [German] Unter dem Begriff ''oellose Kompressoren'' versteht man Verdichter, die in der ganzen Anlage keinen Tropfen Oel verwenden, weder im Fuehrungs- und Verdichtungstell noch im Triebwerk. Die Schmierung erfolgt mit speziellen Materiallen im Trockenlauf. Die Technik der oellosen und trockenlaufenden Kolbenkompressoren wurde bereits vor rund 35 Jahren von der schweizer Firma Fritz Haug AG entwickelt. Anfaenglich war die Anwendung der Verdichtung von Luft auf 10 bis 40 bar vorbehalten. Durch Weiterentwicklungen in neue Materiallen und in der Konstruktion besteht heute auch ein umfangreiches Sortiment an Kompressoren fuer die oellose und trockene Verdichtung von Gasen fuer den Nieder- und Hochdruckbereich. (orig.)

  19. Aggregating territories, integrating elites. The Southern Netherlands and the Monarchy of Philip III (1598-1621

    Directory of Open Access Journals (Sweden)

    Alicia ESTEBAN ESTRÍNGANA

    2011-07-01

    Full Text Available Normal 0 21 false false false ES X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi; mso-fareast-language:EN-US;} This article studies how Philip III managed his royal patronage in the years before the return of the Southern Netherlands into the Spanish sovereignty in 1621 (honours, grants, court offices, military habits. The king tried to assure the success of this return stimulating and satisfying the profits expectancies of the Flemish elites, who could see this return as a positive decision for their interests. The details of the elites integration politics designed and implemented by the Crown to bring back this former patrimonial territory to the Spanish Monarchy demonstrate the practical values of some forms of belonging and some goals of identity adherence, as a service at the Royal Houses or the Catholicism’s defence.

  20. Linkage between seasonal insolation gradient in the tropical northern hemisphere and the sea surface salinity of the equatorial Indian Ocean during the last glacial period

    Digital Repository Service at National Institute of Oceanography (India)

    Saraswat, R.; Nigam, R.; Mackensen, A.; Weldeab, S.

    ) Centennial scale climate instabilities in a wet early Holocene West African monsoon. Geophys Res Lett 34: L24702, doi:10.1029/2007GL031898. Yancheva G, Nowaczyk NR, Mingram J, Dulski P, Schettler G, Negendank JFW, Liu J, Sigman DM, Peterson LC, Haug GH...

  1. Flight Attendant Fatigue, Part 1: National Duty, Rest, and Fatigue Survey

    Science.gov (United States)

    2009-12-01

    Wegmann, 1995; ewing, 1999; haugli, Skogstad, and hellesoy, 1994; hunt and Space, 1994; nagda and koontz , 2003; rayman, 1997; Smolensky, lee, Mott, and...nagda, n .l ., & koontz , M .d . (2003) . review of studies on flight attendant health and comfort in airliner cabins . Aviation, Space

  2. President Arnold Rüütel siirdas Kalevipojale südame / Meelis Lainvoo

    Index Scriptorium Estoniae

    Lainvoo, Meelis

    2003-01-01

    Rakvere Teatri suvelavastuse "Kalevipoeg" viimasel etendusel osalesid Arnold ja Ingrid Rüütel ning poliitikud Tõnis Palts, Tõnis Lukas, Arvo Haug ja Tõnu Kõiv. President Arnold Rüütel pani Neerutis Sadulamäel Kalevipoja kujule viimase kivi. Skulptuuri autori Seaküla Simsoni kommentaar

  3. Law and Power in the Middle Ages

    DEFF Research Database (Denmark)

    International konferenceantologi med bidrag fra Gerd Althoff, Dominique Bauer, Bruce C Brasington, Charlotte Christensen-Nugues, Michael H Gelting, John Gillingham, Eldbjørg Haug, John Hudson, Brigitte Meijns, Hans Jacob Orning, Anne Irene Riisøy, Matthew Strickland, Jo Rune Ugulen, og Sally N Va...

  4. Structurally bound sulfide and sulfate in apatite from the Philips Mine iron oxide - apatite deposit, New York, USA: A tracer of redox changes

    Science.gov (United States)

    Sadove, G.; Konecke, B.; Fiege, A.; Simon, A. C.

    2017-12-01

    Multiple competing hypotheses attempt to explain the genesis of iron oxide-apatite (IOA) ore deposits. Many studies have investigated the chemistry of apatite because the abundances of F and Cl can distinguish magmatic vs. hydrothermal processes. Recent experiments demonstrate that apatite incorporates S6+, S4+, and S2-, and that total sulfur (∑S) as well as the S6+/∑S ratio in apatite vary systematically as a function of oxygen fugacity [1], providing information about sulfur budget and redox. Here, we present results from X-ray absorption near-edge structure (XANES) spectroscopy at the S K-edge, electron microprobe analyses, cathodoluminescence (CL) imaging, and element mapping of apatite from the Philip's Mine IOA deposit, southern Adirondack Mountains, USA. The Philip's Mine apatite contains inclusions of pyrite and pyrrhotite, where the latter includes iron oxide and Ni-rich domains. The apatite also contains inclusions of monazite, and exhibits complex CL zonation coincident with variations in the abundances of REE and S. The presence of monazite fingerprints fluid-mediated dissolution-reprecipitation of originally REE-enriched apatite [2]. The S XANES spectra reveal varying proportions of structurally bound S6+ and S2-, as the S6+/∑S ratio ranges from sulfide-only to sulfate-only. Notably, sulfide-dominated domains contain higher S contents than sulfate-dominated regions. These observations are consistent with co-crystallization of apatite and monosulfide solid solution (MSS) at reducing conditions, followed by decomposition of MSS to pyrrhotite, pyrite and intermediate solid solution (ISS, which is not preserved; [3]). Metasomatism of that assemblage by an oxidized fluid resulted in formation of monazite in apatite and iron oxide domains in pyrrhotite. We conclude that the deposit formed by a H2S-Fe-rich volatile phase, possibly evolved from a rather primitive magmatic source, which is consistent with the low Ti content of magnetite. The deposit was

  5. Two Millian Arguments: Using Helen Longino’s Approach to Solve the Problems Philip Kitcher Targeted with His Argument on Freedom of Inquiry

    Directory of Open Access Journals (Sweden)

    Jaana Eigi

    2012-12-01

    Full Text Available Philip Kitcher argued that the freedom to pursue one's version of the good life is the main aim of Mill's argument for freedom of expression. According to Kitcher, in certain scientific fields, political and epistemological asymmetries bias research toward conclusions that threaten this most important freedom of underprivileged groups. Accordingly, Kitcher claimed that there are Millian grounds for limiting freedom of inquiry in these fields to protect the freedom of the underprivileged.I explore Kitcher's argument in light of the interpretation Helen Longino gave to Mill's argument. She argued that free critical dialogue in the community allows bias to be overcome, through intersubjective criticism of hypotheses and the background assumptions that frame them.I suggest that Longino's approach allows for the identification of the fundamental problems of the research programs Kitcher targeted, and for the rejection of their claims to knowledge. Thus it is possible to address Kitcher's problem without limiting freedom of speech.

  6. EFECTO DE DOS TIPOS DE FUNDAS SOBRE EL FRUTO DE BANANO (Musa AAA

    Directory of Open Access Journals (Sweden)

    Alfonso Vargas-Calvo

    2011-01-01

    Full Text Available El objetivo de este estudio fue determinar el efecto de dos fundas en la protección del racimo de banano (Musa AAA . En dos épocas climáticas (adversa y favorable bajo condiciones del Ca ribe de Costa Ri ca se evaluaron dos fundas: 1- azul Sa nta Lucía (bifentrina 0,1%, polie tileno de 12,7 ¿ de grosor, con perforaciones de 4 mm y 86,4 cm de ancho y 2- transparente con aditivos para filtrar la luz ultravioleta e infrarroja (bifentrina 0,1%, 20,3 ¿ de grosor, con perforaciones de 4 mm y 88,9 cm de ancho. El peso del racimo así como el grosor y la longitud del fruto central de la fila externa en la segunda, cuarta y sexta mano no difirieron (P> 0,0556 entre ambas fundas. Tampoco hubo diferencias entre estas en la apa rie ncia del racimo (P>0,4699 ni en la firmeza de la cáscara en grado 1 de maduración (P= 0,6268. En las varia bles de medición del color del fruto solamente L* presentó un valor (56,48 más alto (P=0,0109 con la funda transparente fotosensible, mie ntras que las otras dos varia bles relacionadas (a* y b* no fueron diferentes (P>0,1011 entre las fundas. El incremento adicional de 7,6 ¿ en el grosor del polie tileno de la funda transparente con respecto a la azul Sa nta Lucía, no ocasionó un incremento productivo ni una mejor apa rie ncia del racimo de banano y sus frutos.

  7. Design of experiments in medical physics: Application to the AAA beam model validation.

    Science.gov (United States)

    Dufreneix, S; Legrand, C; Di Bartolo, C; Bremaud, M; Mesgouez, J; Tiplica, T; Autret, D

    2017-09-01

    The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y 1 and Y 2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the AAA algorithm. The same raw data was used for all accelerators during the beam modelling. The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  8. "Santa Maria" forever : Eesti ja Portugali kirjandussuhetest / Toomas Haug

    Index Scriptorium Estoniae

    Haug, Toomas, 1956-

    2012-01-01

    Jaanuaris 1961 Portugali diktaatorlikule režiimile protestiks kaaperdatud laevast "Santa Maria", mis sai omamoodi vabaduse ja vastuhaku sümboliks ka okupeeritud Eestis. Artiklis käsitletakse sellest sündmusest mõjutatud teoseid, täpsemalt Aleksander Suumanni maali "Santa Maria" ja Paul-Eerik Rummo samanimelist luuletust

  9. "Santa Maria" forever : Eesti ja Portugali kirjandussuhetest / Toomas Haug

    Index Scriptorium Estoniae

    Haug, Toomas, 1956-

    2015-01-01

    Jaanuaris 1961 Portugali diktaatorlikule režiimile protestiks kaaperdatud laevast "Santa Maria", mis sai omamoodi vabaduse ja vastuhaku sümboliks ka okupeeritud Eestis. Artiklis käsitletakse sellest sündmusest mõjutatud teoseid, täpsemalt Aleksander Suumanni maali "Santa Maria" ja Paul-Eerik Rummo samanimelist luuletust

  10. Collective Biography and Memory Work: Girls Reading Fiction

    Science.gov (United States)

    Gannon, Susanne

    2015-01-01

    Collective biography draws on memory work methods developed initially by feminist sociologists (Haug et al., 1987) where people collaboratively examined the social and discursive resources through which they take themselves up as particular gendered subjects in the world. Their own memories become resources to investigate processes of…

  11. Sarivõistlused ja Medalijaht 2012 / Eduard Pukkonen

    Index Scriptorium Estoniae

    Pukkonen, Eduard, 1960-

    2012-01-01

    2012. aastal lisandus Eesti Orienteerumisliidu juhatuse otsusega olemasolevatele sarjadele Eesti meistrivõistluste medalite kogumise võistlus Medalijaht 2012, mille esimene võitja on Marianne Haug 11 medaliga. 2012. aastal jagati orienteerumisspordis kõigi alade ja võistlusklasside peale välja 744 Eesti meistrivõistluste medalit

  12. Deploying Serious Games for Management in Higher Education: lessons learned and good practices

    NARCIS (Netherlands)

    Baalsrud Hauge, Jannicke; Bellotti, Francesco; Nadolski, Rob; Kickmeier-Rust, Michael; Berta, Riccardo; Carvalho, Maria B.

    2013-01-01

    Baalsrud Hauge, J., Bellotti, F., Nadolski, R. J., Kickmeier-Rust, M., Berta, R., & Carvalho, M. B. (2013). Deploying Serious Games for Management in Higher Education: lessons learned and good practices. In C. Vaz de Carvalho, & P. Escudeiro (Eds.), Proceedings of the 7th European Conference on

  13. Ring peale kultuurkapitali kirjanduslaureaatidele

    Index Scriptorium Estoniae

    2005-01-01

    Eesti Kultuurkapitali 2004. aasta kirjanduse aastapreemia laureaatide teoste tutvustused: André Trinity (Rein Raud "Hector ja Bernard"), Mart Velsker (fs - luulekogu "2004"), Katrin Ruus (Mart Kivastik -näidend "Külmetava kunstniku portree"), Krista Kumberg (Jaan Rannap "Nelja nimega koer"), Rein Veidemann (Toomas Haug "Troojamäe tõotus")

  14. Vares ja kana : [valmid] / Ivan Krõlov ; tlk. Eduard Kansa, Mart Raud, Timotheos Kuusik, Johannes Semper, G. Õis, Arnold Tulik, Oskar Urgart, Jaan Kärner, Jakob Tamm, Erni Hiir

    Index Scriptorium Estoniae

    Krõlov, Ivan, 1768(1769)-1844

    2006-01-01

    Sisu: Vares ja Kana ; Moosekandid ; Vares ja Rebane ; Konn ja Härg ; Pirtsakas Näitsik ; Oraakel ; Rukkilill ; Tuli ja Metsatukk ; Hunt ja Talleke ; Pärdik ja Prillid ; Ahvid ; Tihane ; Eesel ; Kotkas ja Kanad ; Võimumees ja Mõttetark ; Koerte sõprus ; Kasujaotus ; Vaat ; Kvartett ; Teekäijad ja Koerad ; Hunt penilas ; Oja ; Rebane ja Mäger ; Rohutirts ja Sipelgas ; Luiskaja ; Kukk ja Pärlitera ; Jänes jahil ; Hunt ja Kägu ; Haug ja Kass ; Peremees ja Sulane ; Voor ; Elevant maavalitsejaks ; Eesel ja Ööbik ; Külamehe kimbatus ; Elevant ja Mops ; Hunt ja tema Kutsikas ; Kass ja Kokk ; Lõvi ja Sääsk ; Aednik ja Filosoof ; Haned ; Siga ; Vanamees ja kolm noorukit ; Kotkas ja Ämblik ; Lehed ja Juured ; Hunt ja Rebane ; Lohe ; Rästas ; Mehhaanik ; Trishka satter ; Tiik ja Jõgi ; Luik, Haug ja Vähk ; Erak ja Karu ; Mesilane ja Kärbsed ; Lõvi jahisaak ; Talupojad ja Jõgi ; Lilled ; Uudishimulik ; Kaastundlik Rebane ; Kogukonna koosolek ; Demjani kalasupp ; Tihane ja Tuvi ; Hiir ja Rott ; Peegel ja Ahv ; Sääsk ja Karjane ; Talupoeg ja Surm ; Hunt ja Karjased ; Lõvi ja Rebane ; Kamm ; Hunt ja Kurg ; Pilv ; Poiss ja Siug ; Maamees ja Siug ; Kägu ja Tuvike ; Kaks Vaati ; Töökas Karu ; Rebane ja Viinamarjad ; Karu võrgus ; Kirjamees ja Röövel ; Mölder ; Siga Tamme all ; Kärbes ja Mesilane ; Ämblik ja Mesilane ; Rebane ja Eesel ; Siug ja Talleke ; Ööbikud ; Peremes ja Lammas ; Kaks Külameest ; Kaks Koera ; Kass ja Ööbik ; Kalade tants ; Haug ; Habemenoad ; Hiired ; Hunt ja Kass ; Karjane ; Orav ; Damaskuse mõõk ; Koer ja Hobune ; Rebane ; Hundid ja Lambad ; Kägu ja Kukk

  15. Study Design and Data Gathering Guide for Serious Games’ Evaluation

    NARCIS (Netherlands)

    Baalsrud Hauge, Jannicke; Boyle, Elizabeth; Mayer, Igor; Nadolski, Rob; Riedel, Johann C. K. H.; Moreno-Ger, Pablo; Bellotti, Francesco; Lim, Theodore; Ritchie, James

    2013-01-01

    Baalsrud Hauge, J., Boyle, E., Mayer, I., Nadolski, R. J., Riedel, J. C. K. H., Moreno-Ger, P., Bellotti, F., Lim, T., & Ritchie, J. (2013). Study Design and Data Gathering Guide for Serious Games’ Evaluation. In T. M. Connolly, T. Hainey, E. Boyle, G. Baxter, & P. Moreno-Ger (Eds.), Psychology,

  16. Zoroastrianism: The Rediscovery of Missing Chapters in Man's Religious History. Teaching Aids for the Study of Inner Asia, No. 6.

    Science.gov (United States)

    Boyce, Mary

    Some modern scholars of Zoroastrianism, a faith still practiced in Iran and India today, are convinced that the doctrines of post-exilic Judaism and Christianity concerning monotheism, righteousness, and the final judgment and resurrection have roots in this ancient religion. Beginning with Martin Haug, a 19th centurey German philologist, the…

  17. Analysis of MaACS2, a stress-inducible ACC Synthase Gene in Musa acuminata AAA Group Cultivar Pisang Ambon

    Directory of Open Access Journals (Sweden)

    Resnanti Utami Handayani

    2014-07-01

    Full Text Available Ethylene has an important function in plant growth and development. Ethylene production generally increases in response to pathogen attacks and other environmental stress conditions. The synthesis of this phytohormone is regulated by two enzymes, ACC synthase (ACS and ACC oxidase (ACO. ACC synthase is encoded by a multigene that regulates the production of ACC, after which this precursor is converted into ethylene by ACO. Pisang Ambon (Musa sp. AAA group, a banana cultivar originating from Indonesia, has nine ACS genes (MaACS 1-9 and one ACO gene (MaACO. One of the banana ACS genes, MaACS2, is stress-inducible. In this research, we have investigated the expression profile of MaACS2 in the roots and leaf tissues of infected tissue culture plants. Quantification of gene expression was analyzed using Real-Time PCR (qPCR using Ma18srRNA and MaGAPDH as reference genes. The results showed nine-to ten fold higher MaACS2 expression levels in the infected roots tissues compared to the uninfected roots tissues. However, MaACS2 expression in the leaves was only detected in infected tissue.

  18. Different gamma radiation doses effects of 60 Co on buds of banana plant (Nanicao-AAA) breeded in vitro

    International Nuclear Information System (INIS)

    Alves, Gilberto Dias; Colaco, Waldeciro

    1999-01-01

    Buds from banana cv. Nanicao-AAA (3 mm x 3 mm) were aseptically cultured in a modified Murashige and Skoog (MS) basal medium supplement with bezylaminepurine and sucrose, and solidified with agar. Buds placed on sterile Petri dishes were irradiated with increasing gamma rays doses (10, 20, 30, and 40 Gy). The statistical design was completely randomized with 5 doses and 30 replications. After irradiation, buds were transferred to 10 ml of the same medium into test tubes, and allowed to grow in a controlled environment (25 deg C, 16 h illumination ) for 4 weeks. There were no significant differences (Tukey, 0,05) between doses in terms of oxidation: in around 20% for all treatments. On the other hand, a statistically significant decrease in the germination of new buds with increased doses of irradiation was observed. The treatment with 40 Gy reduced in 80% the germination of new buds by the end of the evaluated period (4 weeks), resulting in a mean production of 1,5 buds. Mean production in the control was 7,6 buds. no statistically significant differences were detected between treatments with 10, 20, and 30 Gy, with a mean production of 3 buds, less than half obtained in the control. (author)

  19. "A good personal scientific relationship": Philip Morris scientists and the Chulabhorn Research Institute, Bangkok.

    Directory of Open Access Journals (Sweden)

    Ross Mackenzie

    2008-12-01

    Full Text Available This paper examines the efforts of consultants affiliated with Philip Morris (PM, the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI. A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO Collaborating Centre in December 2005.This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships.The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently

  20. "A good personal scientific relationship": Philip Morris scientists and the Chulabhorn Research Institute, Bangkok.

    Science.gov (United States)

    Mackenzie, Ross; Collin, Jeff

    2008-12-23

    This paper examines the efforts of consultants affiliated with Philip Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005. This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships. The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently awarded status

  1. In-situ monitoring of blood glucose level for dialysis machine by AAA-battery-size ATR Fourier spectroscopy

    Science.gov (United States)

    Hosono, Satsuki; Sato, Shun; Ishida, Akane; Suzuki, Yo; Inohara, Daichi; Nogo, Kosuke; Abeygunawardhana, Pradeep K.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro

    2015-07-01

    For blood glucose level measurement of dialysis machines, we proposed AAA-battery-size ATR (Attenuated total reflection) Fourier spectroscopy in middle infrared light region. The proposed one-shot Fourier spectroscopic imaging is a near-common path and spatial phase-shift interferometer with high time resolution. Because numerous number of spectral data that is 60 (= camera frame rare e.g. 60[Hz]) multiplied by pixel number could be obtained in 1[sec.], statistical-averaging improvement realize high-accurate spectral measurement. We evaluated the quantitative accuracy of our proposed method for measuring glucose concentration in near-infrared light region with liquid cells. We confirmed that absorbance at 1600[nm] had high correlations with glucose concentrations (correlation coefficient: 0.92). But to measure whole-blood, complex light phenomenon caused from red blood cells, that is scattering and multiple reflection or so, deteriorate spectral data. Thus, we also proposed the ultrasound-assisted spectroscopic imaging that traps particles at standing-wave node. Thus, if ATR prism is oscillated mechanically, anti-node area is generated around evanescent light field on prism surface. By elimination complex light phenomenon of red blood cells, glucose concentration in whole-blood will be quantify with high accuracy. In this report, we successfully trapped red blood cells in normal saline solution with ultrasonic standing wave (frequency: 2[MHz]).

  2. Mida loodavad poliitikud? / Urmas Lauri

    Index Scriptorium Estoniae

    Lauri, Urmas, 1956-

    1998-01-01

    Vastavad T. Jürgenson, S. Ivanov, A. Rüütel, A. Haug, O. Anton, Pärnoja, M. Kubo, S. Kallas, K. Kilvet, M. Treial, E. Truu. Järgneb 20. jaan. 1998, lk. 2; 22. jaan. 1998, lk. 2; 27. jaan. 1998, lk. 2. Ilmunud ka: Hiiu Leht, 20. jaan. 1998, lk. 3

  3. Võistlused : [kalasport, 2. märts - 18. mai 2013

    Index Scriptorium Estoniae

    2013-01-01

    EMV kirbutamises 2013, Maardu Ahven 2013, Vagula Kala 2013, Uljaste Triibu 2013, metsameeste talipüügivõistlus 2013, Loosalu Ahven 2013, Saadjärve Tinakala 2013, Kadrina Triibu 2013, Töörahva Kala 2013, Kevadkalake 2013, Saadjärve Haug 2013, Järva KK lahtised meistrivõistlused spinningupüügis 2013

  4. Through tobacco industry eyes: civil society and the FCTC process from Philip Morris and British American Tobacco's perspectives.

    Science.gov (United States)

    Gonzalez, Mariaelena; Green, Lawrence W; Glantz, Stanton A

    2012-07-01

    To analyse the models Philip Morris (PM) and British American Tobacco (BAT) used internally to understand tobacco control non-governmental organizations (NGOs) and their relationship to the global tobacco control policy-making process that resulted in the Framework Convention for Tobacco Control (FCTC). Analysis of internal tobacco industry documents in the Legacy Tobacco Document Library. PM contracted with Mongoven, Biscoe, and Duchin, Inc. (MBD, a consulting firm specialising in NGO surveillance) as advisors. MBD argued that because NGOs are increasingly linked to epistemic communities, NGOs could insert themselves into the global policy-making process and influence the discourse surrounding the treaty-making process. MBD advised PM to insert itself into the policy-making process, mimicking NGO behaviour. BAT's Consumer and Regulatory Affairs (CORA) department argued that global regulation emerged from the perception (by NGOs and governments) that the industry could not regulate itself, leading to BAT advocating social alignment and self-regulation to minimise the impact of the FCTC. Most efforts to block or redirect the FCTC failed. PM and BAT articulated a global policy-making environment in which NGOs are key, non-state stakeholders, and as a result, internationalised some of their previous national-level strategies. After both companies failed to prevent the FCTC, their strategies began to align. Multinational corporations have continued to successfully employ some of the strategies outlined in this paper at the local and national level while being formally excluded from ongoing FCTC negotiations at the global level.

  5. Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

    Directory of Open Access Journals (Sweden)

    Hiren Patt

    2017-11-01

    Full Text Available Objective: To study genotype–phenotype spectrum of triple A syndrome (TAS. Methods: Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8 and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications. Results: Median age at presentation was 4.75 years (range: 4–10 and 5 years (range: 1–42 for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI, achalasia and neurological dysfunction (ND were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC was uncommon (absent in cohort 1, 12.5% in cohort 2. In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45 was commonest, followed by a deletion in exon 8 (p.S255Vfs*36. Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations as compared to NT (non-truncating mutations group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. Conclusion: Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

  6. Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

    Science.gov (United States)

    Patt, Hiren; Koehler, Katrin; Lodha, Sailesh; Yerawar, Chaitanya; Huebner, Angela; Thakkar, Kunal; Arya, Sneha; Nair, Sandhya; Goroshi, Manjunath; Ganesh, Hosahithlu; Sarathi, Vijaya; Lila, Anurag; Bandgar, Tushar; Shah, Nalini

    2017-01-01

    Objective To study genotype–phenotype spectrum of triple A syndrome (TAS). Methods Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). Results Median age at presentation was 4.75 years (range: 4–10) and 5 years (range: 1–42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. Conclusion Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research. PMID:29180348

  7. Gq and Gs signaling acting in synergy to control GLP-1 secretion

    DEFF Research Database (Denmark)

    Pedersen, Maria Hauge; Ekberg, Jeppe Hvidtfeldt; Engelstoft, Maja Storm

    2017-01-01

    GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed i...

  8. Aplikasi Metode Lean Six Sigma Untuk Usulan Improvisasi Lini Produksi Dengan Mempertimbangkan Faktor Lingkungan. Studi Kasus: Departemen GLS (General Lighting Services PT. Philips Lighting Surabaya

    Directory of Open Access Journals (Sweden)

    Miftachul Arifin

    2012-09-01

    Full Text Available Departemen GLS (General Lighting Services PT. Philips Lighting Surabaya merupakan produsen lampu pijar. Pada pelaksanaan proses produksinya, perusahaan menemui beberapa kendala yang terkait dengan waste. Analisis lean six sigma dengan menggunakan value stream mapping menunjukkan terjadi defect di mesin finishing dan waiting di mesin mounting. EHS waste juga muncul yang mengindikasikan adanya dampak terhadap lingkungan dan kesehatan serta keselamatan pekerja. Pencarian akar permasalahan dilakukan dengan menggunakan tools RCA (5 whys dan FMEA hingga memunculkan 15 penyebab utama terjadinya ketiga waste tersebut. Pembentukan tim Total productive maintenance, penelitian perbaikan kualitas bulb dan flare, serta eksperimen pengurangan jumlah jenis coil menjadi usulan alternatif yang bisa dilakukan perusahaan. Dengan menggunakan konsep value management didapatkan alternatif terbaik dengan melakukan pembentukan dan pelatihan tim Total productive maintenance. Alternatif ini meningkatkan nilai sigma defect dari 2,92 menjadi 3,08 dan sigma waiting dari 2,83 menjadi 2,89. Indikator dampak lingkungan juga mengindikasikan penurunan yang sejalan.

  9. Crème de la crème / Joel Sang

    Index Scriptorium Estoniae

    Sang, Joel, 1950-

    2011-01-01

    Auhinnažürii esimees iseloomustab Eesti Kultuurkapitali kirjandusauhindade laureaate: Indrek Koff (luule), Maarja Kangro (proosa), Urmas Vadi (näitekirjandus), Toomas Haug (esseistika), Lauri Sommer (vabaauhind), Amar Annus (ilukirjanduslik tõlge võõrkeelest eesti keelde), Ilmar Lehtpere (ilukirjanduslik tõlge eesti keelest võõrkeelde), Kristiina Kass (lastekirjandus), Sergei Issakov (venekeelse autori kirjandusauhind) ja Mart Velsker (artikliauhind)

  10. Introduction to Free Atoms and Particles.

    Science.gov (United States)

    1986-01-01

    34 Vol. I (R. Abramovitch. ed.). pp. 42. 46. 47. 44. 65, Plenum, New York. 1979. 9. P. L. Timms. in " Cryochemistry " (M. Moskovits and G. Ozin. eds.). p. 61...in ’ Cryochemistry " (M. Moskovits and G. Ozin. eds.). p. 261. * Wiley (interscicnce). New York, 1976. 15. R. H. Hauge, S. E. Grandsen. and J. L

  11. A practical method to standardise and optimise the Philips DoseRight 2.0 CT automatic exposure control system.

    Science.gov (United States)

    Wood, T J; Moore, C S; Stephens, A; Saunderson, J R; Beavis, A W

    2015-09-01

    Given the increasing use of computed tomography (CT) in the UK over the last 30 years, it is essential to ensure that all imaging protocols are optimised to keep radiation doses as low as reasonably practicable, consistent with the intended clinical task. However, the complexity of modern CT equipment can make this task difficult to achieve in practice. Recent results of local patient dose audits have shown discrepancies between two Philips CT scanners that use the DoseRight 2.0 automatic exposure control (AEC) system in the 'automatic' mode of operation. The use of this system can result in drifting dose and image quality performance over time as it is designed to evolve based on operator technique. The purpose of this study was to develop a practical technique for configuring examination protocols on four CT scanners that use the DoseRight 2.0 AEC system in the 'manual' mode of operation. This method used a uniform phantom to generate reference images which form the basis for how the AEC system calculates exposure factors for any given patient. The results of this study have demonstrated excellent agreement in the configuration of the CT scanners in terms of average patient dose and image quality when using this technique. This work highlights the importance of CT protocol harmonisation in a modern Radiology department to ensure both consistent image quality and radiation dose. Following this study, the average radiation dose for a range of CT examinations has been reduced without any negative impact on clinical image quality.

  12. Impact of abdominal aortic aneurysm screening on quality of life

    OpenAIRE

    Bath, M. F.; Sidloff, D.; Saratzis, A.; Bown, M. J.

    2018-01-01

    Background Screening for abdominal aortic aneurysm (AAA) is known to reduce AAA‐related mortality; however, the psychological impact of population AAA screening is unclear. The aim was to assess the impact of AAA diagnosis on quality of life (QoL) using data from an established AAA screening programme. Methods Mental and physical QoL scores for men diagnosed with AAA through participation in the English and Welsh AAA screening programmes were compared with no‐AAA controls. Participants were i...

  13. Staff members' perceptions of an animal-assisted activity.

    Science.gov (United States)

    Bibbo, Jessica

    2013-07-01

    To examine the perceptions of staff members toward the implementation of an animal-assisted activity (AAA) in an outpatient regional cancer center. Quasi-experimental, post-test design. An adult outpatient regional cancer center in northern California. 34 facility staff members. Self-report questionnaire following four weeks of AAA visitation. Visits took place three times a week for a total of 12 visits. Perceptions of the AAA. Previous perceptions toward AAA influenced the perceptions of the visitation's efficacy. Direct and indirect interaction with the visiting AAA teams was positively associated with perceptions of the AAA. A disagreement occurred that the AAA had caused extra stress or work for staff. Enjoyment of interacting with the dog handler was not significantly different from interacting with the dog; however, it was more positively correlated to acceptance of the AAA. The study provided evidence that the AAA was generally accepted by staff members. Individual staff members' perceptions of dogs and AAAs can influence their receptivity to AAA interventions. Interaction with AAA teams should be voluntary and available for patients and staff members. AAA may be introduced into facilities without creating the perception of extra stress or work for staff members. Providing staff the opportunity to interact with visiting AAA teams may be beneficial for the success of such programs. The human handler in AAA teams may play a vital role in the staff acceptance of such programs.

  14. Descripción morfoagronómica de materiales de plátano (Musa AAB, ABB y banano (Musa AAA cultivados en San Andrés Isla Morpho-agronomic Description of Plantain (Musa AAB, ABB and Banana (Musa AAA Materials Grown in San Andres Island

    Directory of Open Access Journals (Sweden)

    Oscar Javier Parra Pachón

    2009-10-01

    Full Text Available Durante el primer semestre de 2005 se estudiaron los cultivares de plátano y banano en fincas y parcelas de 15 agricultores típicos participantes en programas conjuntos de la Secretaría de Agricultura y Pesca de San Andrés Isla y de la Universidad Nacional de Colombia sede Caribe. A partir de descriptores de INIBAP, IPGRI y CIRAD y revisiones bibliográficas.se describen morfológicamente los materiales de Musa cultivados en la Isla, así como las prácticas de los productores isleños, Se identificaron cuatro clones del subgrupo plátano (Musa AAB: un Hartón (‘Horse’ y tres Dominico-Hartón (‘Tallo Negro’, ‘Tallo Blanco’ y ‘Cincuenta’ del subgrupo ABB se hallaron un material de Bluggoe (‘Boscó’ y un Felipita. El subgrupo banano AAA presentó dos materiales Gros Michel (denominados Común y Chino y uno de banano (Rojo. El plátano tiene gran importancia para los agricultores de la Isla, siendo el Boscó el clon más aceptado entre consumidores por su adaptación a las condiciones edafológicas y climáticas. El banano es menos cultivado; ya que los suelos, el clima y las enfermedades como sigatoka negra, condicionaron el desarrollo de clones. El trabajo sugiere prácticas de fácil implementación que podrían aumentar la producción en los sistemas de huerto mixto tropical que predominan en la Isla.During the first semester, 2005 we studied the plantain and banana cultivars in small farms of 15 volunteer regular producers, who were participating in joint programs of the Agriculture and Fisheries Secretariat of San Andres Island and the Colombian National University Caribbean Headquarters. We described morphologically the Musa cultivars identified in the island, as well as agricultural practices of the island producers, using the INIBAP, IPGRI and CIRAD (1996 descriptors and bibliographical reviews. We identified four clones within the plantain sub-group Musa AAB: a Horn type and three French-Horn; and within the ABB

  15. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Juul, Søren; Henneberg, E W

    1997-01-01

    In spite of increasing number of elective resections of abdominal aortic aneurysms (AAA) the mortality or ruptured AAA is increasing. The advantages of elective operations are obvious; the lethality is 2-6% while the lethality of ruptured AAA is 75-95%. However, AAA seldom causes symptoms before...... rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...

  16. Obituary: Philip M. Solomon, 1939-2008

    Science.gov (United States)

    Scoville, Nick

    2009-01-01

    Philip Solomon, one of the pioneers and leading researchers in molecular astrophysics, died on 30 April 2008 at his apartment on the upper west side of Manhattan after a battle with cancer. His pioneering research included both theoretical and very extensive observational studies of stellar atmospheres, interstellar molecules, high redshift galaxies, and the Earth's stratosphere. Phil was Distinguished Professor at The State University of New York [SUNY], Stony Brook, where he had been since 1974. Phil was born on 29 March 1939 in Manhattan, New York City, to Nat and Betty Solomon. Nat Solomon was a labor organizer and a printer. Phil attended the University of Wisconsin, where he received his BS in 1959 and where he met his future wife Sheila who was studying art. His Ph.D., "On the Role of Light Molecules in Astrophysics," was also from the University of Wisconsin under the guidance of Art Code and Bob Bless. After postdoctoral positions at Princeton and lectureships at Columbia and the University of California, San Diego, Phil spent two years as a Professor at the University of Minnesota. After two years at the Institute for Advanced Study in Princeton, he came to SUNY, Stony Brook, as Professor of Astronomy in the Department of Earth and Space Sciences. In 1988 Phil was selected as a Humboldt Senior Distinguished Scientist, and, in 1999, he was honored with the rank of Distinguished Professor at SUNY. Phil took sabbatical and other leaves at Churchill College and the Institute of Astronomy, Cambridge; the Institute for Advanced Study; l'Ecole Normale Superieure, Paris; Institut d'Astrophysique, Paris; and the Institut de Radioastronomie Millimetrique [IRAM], France. Phil published more than 160 papers and supervised seven Ph.D. students. He served on numerous review, visiting, and advisory panels. Phil's first theoretical research focused on opacity and abundance of light molecules such as H2, CO, and CN in stellar atmospheres, but then shifted quickly to the

  17. Association of ficolin-3 with abdominal aortic aneurysm presence and progression

    DEFF Research Database (Denmark)

    Fernandez-García, C-E; Burillo, E; Lindholt, J S

    2017-01-01

    Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3...... plasma levels are associated with AAA presence and progression. SUMMARY: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA...... pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from...

  18. Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

    Science.gov (United States)

    Kim, Ha Won; Blomkalns, Andra L; Ogbi, Mourad; Thomas, Manesh; Gavrila, Daniel; Neltner, Bonnie S; Cassis, Lisa A; Thompson, Robert W; Weiss, Robert M; Lindower, Paul D; Blanco, Victor M; McCormick, Michael L; Daugherty, Alan; Fu, Xiaoming; Hazen, Stanley L; Stansfield, Brian K; Huo, Yuqing; Fulton, David J; Chatterjee, Tapan; Weintraub, Neal L

    2017-12-01

    Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl 2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration. NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation

  19. Through tobacco industry eyes: civil society and the FCTC process from Philip Morris and British American Tobacco’s perspectives

    Science.gov (United States)

    Gonzalez, Mariaelena; Green, Lawrence W; Glantz, Stanton A

    2011-01-01

    Objective To analyse the models Philip Morris (PM) and British American Tobacco (BAT) used internally to understand tobacco control non-governmental organizations (NGOs) and their relationship to the global tobacco control policy-making process that resulted in the Framework Convention for Tobacco Control (FCTC). Methods Analysis of internal tobacco industry documents in the Legacy Tobacco Document Library. Results PM contracted with Mongoven, Biscoe, and Duchin, Inc. (MBD, a consulting firm specialising in NGO surveillance) as advisors. MBD argued that because NGOs are increasingly linked to epistemic communities, NGOs could insert themselves into the global policy-making process and influence the discourse surrounding the treaty-making process. MBD advised PM to insert itself into the policy-making process, mimicking NGO behaviour. BAT’s Consumer and Regulatory Affairs (CORA) department argued that global regulation emerged from the perception (by NGOs and governments) that the industry could not regulate itself, leading to BAT advocating social alignment and self-regulation to minimise the impact of the FCTC. Most efforts to block or redirect the FCTC failed. Conclusions PM and BAT articulated a global policy-making environment in which NGOs are key, non-state stakeholders, and as a result, internationalised some of their previous national-level strategies. After both companies failed to prevent the FCTC, their strategies began to align. Multinational corporations have continued to successfully employ some of the strategies outlined in this paper at the local and national level while being formally excluded from ongoing FCTC negotiations at the global level. PMID:21636611

  20. Abdominal aortic aneurysm development in men following a "normal" aortic ultrasound scan.

    Science.gov (United States)

    Hafez, H; Druce, P S; Ashton, H A

    2008-11-01

    To determine predictors related to abdominal aortic aneurysm (AAA) development following a "normal" aortic ultrasound scan. Over a 23-year period, 22 961 men participated in an AAA screening programme. Maximum aortic diameter of less than 30 mm was deemed "normal". 4308 of these "normal" individuals were later re-scanned at intervals for research purposes. AAA prevalence was 4.4% at initial scanning. In those with a normal scan, 46 patients subsequently presented with AAAs incidentally detected and 120 (2.8%) had AAAs identified as part of the ongoing surveillance. The median initial aortic size of these 166 men was 25 mm (range 15-29 mm). Over the follow-up period, there have been 24 (14%) AAA-related deaths, 24 patients underwent successful AAA surgery and 36 died of unrelated causes. In those with an initial aortic diameter of <25 mm who later developed an AAA, the odds ratio for AAA-related mortality was 2 (95% CI 1-4.1, p=0.03, x(2)). AAAs can develop following an initial "normal" scan and men with an aortic diameters of 25-29 mm appear to be at greater risk. Surveillance for this sub-group may further reduce the incidence of undiagnosed AAA and AAA-related mortality.

  1. Foreløbige resultater af screening for abdominalt aortaaneurisme i Viborg Amt

    DEFF Research Database (Denmark)

    Lindholt, J S; Fasting, H; Henneberg, E W

    1997-01-01

    The incidence of abdominal aortic aneurysms (AAA) and ruptured AAA is increasing. One to three percent of deaths among 65-80 year-old males are caused by AAA. Sixty-six to ninety-five percent of ruptured AAA are lethal, while elective resection has a 3-6% operative mortality. Most AAA's are asymp...

  2. Kriteerium - märkimisväärne / Madli Pesti

    Index Scriptorium Estoniae

    Pesti, Madli, 1980-

    2006-01-01

    5.-21. maini Berliinis toimunud festivalist Theatertreffen. Vaatluse all lavastused - Friedrich Schilleri näidenditriloogia "Wallenstein" põhjal tehtud dokumentaalne lavastus (autorid Helgard Haug ja Daniel Wetzel), "Der Kick" ("Löök", lavastaja Andreas Veiel), ameerika koreograafi William Forsythe'i tantsulavastus "The Atmospheric Studies", Dimiter Gotscheffi Tshehhovi tõlgendus "Ivanov", Jürgen Goschi Macbeth" ja "Kolm õde" ning Thomas Ostermeieri Ibseni tõlgendus "Hedda Gabler"

  3. MFA Graduate Show 2015: In the Usual Direction of Travel

    OpenAIRE

    2015-01-01

    Avgangsstudenter: Patrik Berg, Christian Magnus Tømmeraas Berg, Maia Birkeland, Matilda Björkne, Stine Bråthen, Stein Are Kjærås Dahl, Emil Gustafsson, Jeanett Gustavsen, hÅkon gÅre, Jørgen Frederik Scheel Haarstad, Anita Hanch-Hansen, Elin Hedberg, Andrea Wikhammer Heir, Steinar Laumann, Aron-Irving Li, Tina Lindvall, Rebecca Szabo Onstad, Zahra Rashid, Hege Cathrine Hauge Thoresen

  4. A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals

    Science.gov (United States)

    Parthasarathy, Anutthaman; Cross, Penelope J.; Dobson, Renwick C. J.; Adams, Lily E.; Savka, Michael A.; Hudson, André O.

    2018-01-01

    Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type

  5. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.

    Science.gov (United States)

    Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A

    2016-09-19

    Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing.

    Science.gov (United States)

    Yoshikatsu, Yuki; Ishida, Yo-ichi; Sudo, Haruka; Yuasa, Keizo; Tsuji, Akihiko; Nagahama, Masami

    2015-08-28

    Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosome complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Ultrastructural changes and the distribution of arabinogalactan proteins during somatic embryogenesis of banana (Musa spp. AAA cv. 'Yueyoukang 1').

    Science.gov (United States)

    Pan, Xiao; Yang, Xiao; Lin, Guimei; Zou, Ru; Chen, Houbin; Samaj, Jozef; Xu, Chunxiang

    2011-08-01

    A better understanding of somatic embryogenesis in banana (Musa spp.) may provide a practical way to improve regeneration of banana plants. In this study, we applied scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to visualize the ultrastructural changes during somatic embryogenesis of banana (Musa AAA cv. 'Yueyoukang 1'). We also used histological and immunohistochemical techniques with 16 monoclonal antibodies to study the spatial distribution and cellular/subcellular localization of different arabinogalactan protein (AGP) components of the cell wall during somatic embryogenesis. Histological study with periodic acid-Schiff staining documented diverse embryogenic stages from embryogenic cells (ECs) to the late embryos. SEM revealed a mesh-like structure on the surface of proembryos which represented an early structural marker of somatic embryogenesis. TEM showed that ECs were rich in juvenile mitochondria, endoplasmic reticulum and Golgi stacks. Cells in proembryos and early globular embryos resembled ECs, but they were more vacuolated, showed more regular nuclei and slightly more developed organelles. Immunocytochemical study revealed that the signal of most AGP epitopes was stronger in starch-rich cells when compared with typical ECs. The main AGP component in the extracellular matrix surface network of banana proembryos was the MAC204 epitope. Later, AGP immunolabelling patterns varied with the developmental stages of the embryos. These results about developmental regulation of AGP epitopes along with developmental changes in the ultrastructure of cells are providing new insights into the somatic embryogenesis of banana. Copyright © Physiologia Plantarum 2011.

  8. An examination of the effect on cigarette prices and promotions of Philip Morris USA penalties to stores that sell cigarettes to minors.

    Science.gov (United States)

    Feighery, E C; Schleicher, N C; Ribisl, K M; Rogers, T

    2009-12-01

    The purpose of this study was to assess the potential impact of public policies to regulate price discounting strategies on retail cigarette prices and advertising. Philip Morris USA (PM USA) has a policy designed to sanction stores violating state laws banning illegal tobacco sales to minors by temporarily suspending price discounting incentives. This study examined the impact of those sanctions on retail cigarette prices and sales promotion advertising. In November 2006, the California Attorney General's Office informed PM USA that 196 stores were found guilty of illegal underage sales. Of these, 109 stores that participated in the PM USA Retail Leaders Program were notified that their merchandising and/or promotional resources would be suspended for the month of April 2007. The remaining 87 stores were not sanctioned and served as a comparison group. Trained raters assessed advertising and prices of selected PM USA brands in these stores pre-penalty and during the penalty phase. There were no significant differences between sanctioned and non-sanctioned stores on median changes in price and sales promotion advertising from the pre-penalty to the penalty phase. The lack of impact on cigarette prices and advertising indicate that the PM USA policy may be flawed in its design or execution. If public policies are developed to restrain cigarette price discounting strategies, they should be crafted to ensure compliance and preclude possible compensatory actions by retailers.

  9. Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

    Science.gov (United States)

    Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef

    2011-01-01

    Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low

  10. Microsatellite association with seed protein content and flowering ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... 5'-AAA ATC GGG GAA GGA AAC C-3'. (AG). 186. 5'-GAA GGC AAA ATA CAT GGA GTC AC-3'. VM 71. 5'-TCG TGG CAG AGA ATC AAA GAC AC-3'. (AG). 225. 5'-TGG GTG GAG GCA AAA ACA AAA C-3'. (AAAG) amplified multiple bands and were not used for further analysis. One primer pair (SSR-6243) ...

  11. Analysis and computer program for rupture-risk prediction of abdominal aortic aneurysms

    Directory of Open Access Journals (Sweden)

    Li Zhonghua

    2006-03-01

    Full Text Available Abstract Background Ruptured abdominal aortic aneurysms (AAAs are the 13th leading cause of death in the United States. While AAA rupture may occur without significant warning, its risk assessment is generally based on critical values of the maximum AAA diameter (>5 cm and AAA-growth rate (>0.5 cm/year. These criteria may be insufficient for reliable AAA-rupture risk assessment especially when predicting possible rupture of smaller AAAs. Methods Based on clinical evidence, eight biomechanical factors with associated weighting coefficients were determined and summed up in terms of a dimensionless, time-dependent severity parameter, SP(t. The most important factor is the maximum wall stress for which a semi-empirical correlation has been developed. Results The patient-specific SP(t indicates the risk level of AAA rupture and provides a threshold value when surgical intervention becomes necessary. The severity parameter was validated with four clinical cases and its application is demonstrated for two AAA cases. Conclusion As part of computational AAA-risk assessment and medical management, a patient-specific severity parameter 0

  12. Familiære abdominale aortaaneurismer

    DEFF Research Database (Denmark)

    Mejnert Jørgensen, Trine; Lindholt, Jes S.; Høgh, Annette Langager

    Formål og baggrund: Det er velkendt, at risikoen for at udvikle et abdominalt aortaaneurisme (AAA) er væsentligt forøget blandt førstegradsslægtninge til AAA-patienter, men tidligere studier er få og svært sammenlignelige, ligesom man ikke har kunnet belyse, om familiære tilfælde af AAA fremtræder...... mere aggressivt end ikke-familiære. Man ved således meget lidt om væksthastighed, prognose for ruptur, alder ved diagnose og operation og risiko for AAA-relaterede dødsfald for denne gruppe. Projektet vil forsøge at besvare følgende: Hvor stor er forekomsten af AAA blandt førstegradsslægtninge til AAA......-patienter på landsplan og er familiære tilfælde af AAA mere aggressive i form af lavere gennemsnitsalder ved diagnose og operation, hurtigere vækstrate, større rupturrisiko og højere forekomst af AAA-relaterede dødsfald end ikke-familiære AAA? Design: Projektet er et retrospektivt case-kontrolstudie, hvor man...

  13. Statin use and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, H; Høgh, A; Hundborg, H H

    2014-01-01

    BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is associated with high mortality. Research suggests that statins may reduce abdominal aortic aneurysm (AAA) growth and improve rAAA outcomes. However, the clinical impact of statins remains uncertain in relation to both the risk and prognosis...... of rAAA. METHODS: This nationwide, population-based, combined case-control and follow-up study included all patients (aged at least 50 years) with a first-time hospital admission for rAAA and 1:1 matched AAA controls without rupture in Denmark from 1996 to 2008. Individual-level data on preadmission...... drug use, co-morbidities, socioeconomic markers, healthcare contacts and death were obtained from Danish nationwide registries. RESULTS: The study included 3584 cases and 3584 matched controls. Current statin use was registered for 418 patients with rAAA (11.7 per cent) and 539 AAA controls (15.0 per...

  14. ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

    DEFF Research Database (Denmark)

    Burillo, Elena; Lindholt, Jes S.; Molina-Sánchez, Pedro

    2015-01-01

    proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3-5 cm) vs large AAA] using iTRAQ labelling, high-throughput nano-LC-MS/MS and a novel multi-layered statistical model. Among the proteins identified, ApoA-I was decreased in patients...... with large AAA compared to those with small AAA. These results were validated by ELISA on plasma samples from small (n=90) and large AAA (n=26) patients (150± 3 vs 133± 5 mg/dl, respectively, plevels strongly correlated with HDL-Cholesterol (HDL-C) concentration (r=0.9, p....89± 2.99 vs 1.59± 5.74 mmol/l, plevels are negatively associated with AAA evolution. Therapies targeting...

  15. No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder.

    Directory of Open Access Journals (Sweden)

    Catharina Elisabeth Bergwerff

    Full Text Available The aim of the current study was to explore the role of aromatic amino acids (AAAs in blood in relation to attention-deficit/hyperactivity disorder (ADHD. Given their impact on the synthesis of serotonin and dopamine, decreased concentrations of the AAAs tryptophan, tyrosine and phenylalanine in blood may contribute to the expression of ADHD symptoms. Decreased AAA blood concentrations, in turn, may be related to lowered dietary protein intake or to abnormal AAA catabolism, as evidenced by increased urinary AAA concentrations.Eighty-three children with ADHD (75% males and 72 typically developing (TD children (51% males, aged 6 to 13 years, participated in the study. AAA concentrations were assessed in blood spots and an 18-hour urinary sample. A nutritional diary was filled out by parents to calculate dietary protein intake. Parent and teacher questionnaires assessed symptoms of ADHD, oppositional defiant disorder, conduct disorder, and autism spectrum disorder.Children with ADHD showed normal AAA concentrations in blood spots and urine, as well as normal protein intake compared to controls. No associations between AAA concentrations and symptoms of ADHD or comorbid psychiatric disorders were found.This study is the first to explore AAA metabolism in children with ADHD using a well-defined and relatively large sample. We found that AAA deficiencies are not related to ADHD. The results do not support treatment with AAA supplements in children with ADHD. Future studies regarding the cause of serotonin and dopamine alterations in ADHD should focus on other explanations, such as effects of altered transport of AAAs.

  16. Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Zhou, Yi; Wu, Wenxue; Lindholt, Jes S

    2015-01-01

    concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P Pearson's correlation test demonstrated a significant but negative correlation between Foxp3 and AAA annual expansion rate before...... (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P

  17. Losartan prevents from the formation and interferes with the development of calcium chloride-induced abdominal aortic aneurysms

    International Nuclear Information System (INIS)

    Yan Huimin; Cui Bing; Yang Hongzhen; Hu Zhuowei; Chen Zhong; Tang Xiaobin

    2010-01-01

    Objective: Abdominal aortic aneurysm (AAA), a chronic inflammatory vascular disorder, results in progressive expansion and rupture of the aorta with high mortality among the elderly. Multiple factors contribute to the pathogenesis of AAA that somehow induces aneurysmal manifestations. There are no effective drugs available currently. This study aims to find out whether losartan, an angiotensin II type 1 receptor (AT1) antagonist, can prevent and treat the CaCl 2 -induced AAA. Methods: We chose periaortic application of 0.5 mol/L CaCl 2 -induced mouse AAA model. Ultrasonographic and histological studies were conducted to evaluate the formation of AAA in mice. Results: Losartan not only protected against the formation of AAA, but also hindered the development of AAA. Losartan reduced aortic expansion and elastic lamina degradation. Conclusion: The prophylactic and therapeutic effects of losartan are associated with the regulation of vascular fibrosis and inflammation. Losartan inhibits the infiltration of inflammatory cells and decreases the expression of several cytokines in the vascular tissue of AAA. Our studies will provide insight into the pathogenesis of AAA induced by CaCl 2 and offer more evidence that losartan has a great potential for the development of therapeutic agents against AAA. (authors)

  18. Proteins associated with the size and expansion rate of the abdominal aortic aneurysm wall as identified by proteomic analysis

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Lindholt, Jes S.; Delbosc, Sandrine

    2010-01-01

    Identification of biomarkers for the natural history of abdominal aortic aneurysms (AAA) holds the key to non-surgical intervention and improved selection for AAA repair. We aimed to associate the basic proteomic composition of AAA wall tissue with the expansion rate and size in patients with AAA....

  19. Assessing the potential risk of rupture of abdominal aortic aneurysms

    International Nuclear Information System (INIS)

    Khan, S.; Verma, V.; Verma, S.; Polzer, S.; Jha, S.

    2015-01-01

    Abdominal aortic aneurysms (AAAs) involve complex interplays between inflammatory and biomechanical factors that can be elucidated with anatomical and functional imaging. Although AAA size has been well-established in the literature to correlate with risk of rupture (and subsequent need for vascular intervention), there are other less-well-known characteristics about AAAs that also contribute to higher risk of rupture. This review focuses on biomechanical, radiological, and epidemiological characteristics of AAAs that are associated with higher rupture risk. For clinicians, knowing and considering a wide variety of risk factors in addition to AAA size is important to initiate early and proper intervention for AAA repair. Although there is no official quantitative risk score of AAA rupture risk that takes other non-size-related variables into account, if clinicians are aware of these other parameters, it is hoped that intervention can be appropriately performed for higher-risk AAAs that have not met the size-threshold for elective repair

  20. Evaluation of the Analytical Anisotropic Algorithm (AAA) in dose calculation for fields with non-uniform fluences considering heterogeneity correction; Avaliacao do Algoritmo Analitico Anisotropico (AAA) no calculo de dose para campos com fluencia nao uniforme considerando correcao de heterogeneidade

    Energy Technology Data Exchange (ETDEWEB)

    Bornatto, P.; Funchal, M.; Bruning, F.; Toledo, H.; Lyra, J.; Fernandes, T.; Toledo, F.; Marciao, C., E-mail: pricila_bornatto@yahoo.com.br [Hospital Erasto Gaertner (LPCC), Curitiba, PR (Brazil). Departamento de Radioterapia

    2014-08-15

    The purpose of this study is to evaluate the calculation of dose distribution AAA (Varian Medical Systems) for fields with non-uniform fluences considering heterogeneity correction. Five different phantoms were used with different density materials. These phantoms were scanned in the CT BrightSpeed (©GE Healthcare) upon the array of detectors MAPCHECK2 TM (Sun Nuclear Corporation) and irradiated in a linear accelerator 600 CD (Varian Medical Systems) 6MV and rate dose 400MU/min with isocentric setup. The fluences used were exported from IMRT plans, calculated by ECLIPSE™ planning system (Varian Medical Systems), and a 10x10 cm{sup 2} field to assess the heterogeneity correction for uniform fluence. The measured dose distribution was compared to the calculated by Gamma analysis with approval criteria of 3% / 3 mm and 10% threshold. The evaluation was performed using the software SNCPatient (Sun Nuclear Corporation) and considering absolute dose normalized at maximum. The phantoms best performers were those with low density materials, with an average of 99.2% approval. Already phantoms with plates of higher density material presented various fluences below 95% of the points approved. The average value reached 94.3%. It was observed a dependency between fluency and approved percentage points, whereas for the same fluency, 100% of the points have been approved in all phantoms. The approval criteria for IMRT plans recommended in most centers is 3% / 3mm with at least 95% of points approved, it can be concluded that, under these conditions, the IMRT plans with heterogeneity correction can be performed , however the quality control must be careful because the difficulty of the system to accurately predict the dose distribution in certain situations. (author)

  1. Tumedad ained kirjanduses ja päriselt / Mare Müürsepp

    Index Scriptorium Estoniae

    Müürsepp, Mare

    2007-01-01

    Analüüsitud on Philip Pullmani triloogiasse "Tema tumedad ained" kuuluvaid romaane : Pullman, Philip. Kuldne kompass. Tallinn : Tiritamm, 2002; Pullman, Philip. Inglite torn. Tallinn : Tiritamm, 2004; Pullman, Philip. Vaigust kiiker. Tallinn : Tiritamm, 2005

  2. Science, Society, and Social Networking

    Science.gov (United States)

    White, K. S.; Lohwater, T.

    2009-12-01

    The increased use of social networking is changing the way that scientific societies interact with their members and others. The American Association for the Advancement of Science (AAAS) uses a variety of online networks to engage its members and the broader scientific community. AAAS members and non-members can interact with AAAS staff and each other on AAAS sites on Facebook, YouTube, and Twitter, as well as blogs and forums on the AAAS website (www.aaas.org). These tools allow scientists to more readily become engaged in policy by providing information on current science policy topics as well as methods of involvement. For example, members and the public can comment on policy-relevant stories from Science magazine’s ScienceInsider blog, download a weekly policy podcast, receive a weekly email update of policy issues affecting the scientific community, or watch a congressional hearing from their computer. AAAS resource websites and outreach programs, including Communicating Science (www.aaas.org/communicatingscience), Working with Congress (www.aaas.org/spp/cstc/) and Science Careers (http://sciencecareers.sciencemag.org) also provide tools for scientists to become more personally engaged in communicating their findings and involved in the policy process.

  3. The abdominal aortic aneyrism : Clinical outcomes in EVAR and longitudinal biobank studies

    NARCIS (Netherlands)

    Koole, D.

    2013-01-01

    This thesis has been divided in 6 parts. Part I of this thesis focuses on AAA wall biology, rupture risk, and the value of AAA biobanks. Endoluminal stenting is currently the treatment of choice for AAA patients because of the relatively low rate of short-term complications. AAA biopsies from a

  4. TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

    2017-11-01

    Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

  5. Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation

    DEFF Research Database (Denmark)

    Sun, J; Zhang, J; Lindholt, Jes S.

    2009-01-01

    Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown.......Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown....

  6. Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

    Science.gov (United States)

    Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

    2009-08-01

    To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

  7. Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

    Science.gov (United States)

    Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki

    2017-06-03

    Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed AAAs. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC -/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- AAAs compared with WT AAAs at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effect of hydric stress induced by PEG 6000 on water content of Musa spp. ‘Grande naine’ (AAA and ‘Pelipita’ (ABB in vitro plants

    Directory of Open Access Journals (Sweden)

    Leonardo J Moreno-Bermúdez

    2015-10-01

    Full Text Available Bananas and bananas are grown in the tropical and subtropical regions of the world, by hence they are adapted to good humidity conditions. The productivity of these crops is affected by abiotic factors such as drought, which has increased in recent years due to the effects of climate change. In vitro selection of tolerant genotypes offers advantages over field selection as it saves time, resources and permit to work with larger plant volumes. The aim of this work was to determine the effect of in vitro water stress induced with polyethylene glycol 6000 (PEG 6000 on water content (WC of Musa spp. ‘Grande naine’ (AAA and ‘Pelipita’ (ABB cultivars. In ‘Pelipita’ cultivar WC was not affected by PEG 6000 effect, but in ‘Grande naine’ this trait was significantly reduced in those plants under stress. Both, ‘Pelipita’ and ‘Grande naine’ cultivars differentially respond to water stress induced in vitro by PEG 6000 and could be used as reference in plants evaluation obtained by plant breeding for drought tolerance. Key words: banana, climate change, drought, in vitro selection

  9. The accuracy of combined physical examination and ultrasonography for the detection of abdominal aorta aneurysm.

    Science.gov (United States)

    Cârstea, Doina; Streba, Letiţia Adela Maria; Glodeanu, Adina; Cârstea, A P; Vancu, Mihaela; Ninulescu, Ana-Maria

    2008-01-01

    Atherosclerosis is the most frequent cause in the appearance of an abdominal aorta aneurysm (AAA) and plays an important role in his development. Most AAA does not cause any symptoms, especially when talking about elderly patients, however, many of those aneurysms can be detected during physical examination. Their detection is very important because the natural evolution and the major reason in treating AAA is their tendency to rupture. We present the case of an adult man with a complex clinical pathology, but not related to the AAA. The diagnosis of the AAA has been suspicion through palpation, and the abdominal ultrasound exam confirmed it. This case is particular interesting, as the AAA requires surgical intervention, while patient's health status was poor. An essential issue is establishing the importance of the AAA screening, when there are no symptoms present. For now, there are not satisfactory studies to be used as a guide.

  10. Follow-up on Small Abdominal Aortic Aneurysms Using Three Dimensional Ultrasound

    DEFF Research Database (Denmark)

    Ghulam, Q. M.; Bredahl, K. K.; Lönn, L.

    2017-01-01

    Objectives Rupture risk in abdominal aortic aneurysms (AAAs) is assessed using AAA diameter; yet 10% of ruptures occur in a small aneurysm. This underlines the inadequacy of diameter as a standalone parameter. In this prospective follow-up study, ultrasound determined aneurysm diameter was compared...... with aneurysm volume determined by three dimensional ultrasound (3D-US) in a group of 179 AAAs. Design This was a prospective cohort study with repeated diameter and volume measurements by 3D-US. Material and methods In total, 179 patients with small infrarenal AAAs (diameter 30–55 mm) were enrolled......L) were recorded. In post-hoc analysis, it was found that more AAAs with a stable diameter and a growing volume than AAAs with a stable diameter and volume were undergoing aortic repair during follow-up, based on the maximum diameter. Conclusion In this cohort of small AAAs, 40% of patients with a stable...

  11. Biomechanical rupture risk assessment of abdominal aortic aneurysms based on a novel probabilistic rupture risk index.

    Science.gov (United States)

    Polzer, Stanislav; Gasser, T Christian

    2015-12-06

    A rupture risk assessment is critical to the clinical treatment of abdominal aortic aneurysm (AAA) patients. The biomechanical AAA rupture risk assessment quantitatively integrates many known AAA rupture risk factors but the variability of risk predictions due to model input uncertainties remains a challenging limitation. This study derives a probabilistic rupture risk index (PRRI). Specifically, the uncertainties in AAA wall thickness and wall strength were considered, and wall stress was predicted with a state-of-the-art deterministic biomechanical model. The discriminative power of PRRI was tested in a diameter-matched cohort of ruptured (n = 7) and intact (n = 7) AAAs and compared to alternative risk assessment methods. Computed PRRI at 1.5 mean arterial pressure was significantly (p = 0.041) higher in ruptured AAAs (20.21(s.d. 14.15%)) than in intact AAAs (3.71(s.d. 5.77)%). PRRI showed a high sensitivity and specificity (discriminative power of 0.837) to discriminate between ruptured and intact AAA cases. The underlying statistical representation of stochastic data of wall thickness, wall strength and peak wall stress had only negligible effects on PRRI computations. Uncertainties in AAA wall stress predictions, the wide range of reported wall strength and the stochastic nature of failure motivate a probabilistic rupture risk assessment. Advanced AAA biomechanical modelling paired with a probabilistic rupture index definition as known from engineering risk assessment seems to be superior to a purely deterministic approach. © 2015 The Author(s).

  12. Abdominal Aortic Diameter Is Increased in Males with a Family History of Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Mejnert Jørgensen, Trine; Houlind, K; Green, A

    2014-01-01

    and a half times increased prevalence of AAA compared with +FH with male relatives with AAA with an OR of 2.65. CONCLUSIONS: First-degree male relatives of AAA patients have wider aortas and a twofold higher prevalence of AAA compared with the age adjusted background population. The prevalence of AAA...... measurement of maximum antero-posterior aortic diameter. Family history obtained by questionnaire. Multivariate regression analysis was used to test for confounders: age, sex, smoking, comorbidity and medication. RESULTS: From the screened cohort, 569 participants had at least one first degree relative...

  13. The validity of ultrasonographic scanning as screening method for abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Vammen, Sten; Juul, Søren

    1999-01-01

    the sensitivity and specificity of screening for abdominal aortic aneurysms (AAAs) with ultrasonographic scanning (US) is unknown. The aim of the study was to validate US as screening test for AAAs.......the sensitivity and specificity of screening for abdominal aortic aneurysms (AAAs) with ultrasonographic scanning (US) is unknown. The aim of the study was to validate US as screening test for AAAs....

  14. Abdominal aortic aneurysm, arterial stiffening and the role of the intraluminal thrombus

    DEFF Research Database (Denmark)

    Lyck Hansen, Maria; Dahl Thomsen, Marie; Melholt Rasmussen, Lars

    2015-01-01

    PATIENTS AND METHODS: PWV and PWA were measured in male patients with AAA from an ongoing Danish AAA screening trial. Information on blood pressure, medications, BMI and smoking status was obtained at inclusion. RESULTS: In total, 157 patients were included. Mean age was 73 years. Mean AAA size...... was 42.2 mm. Fifty-six of the patients had an intraluminal thrombus, and patients with AAA and ILT had a significantly higher Aix75 than patients with AAA but without ILT (Mean = 28.3 ± 1.4 SEM vs. 24.9 ± 0.81, p=0.027), a difference that was also significant when adjusting for AAA size, blood pressure...... and age. There was no difference in PWV between the groups. CONCLUSIONS: Haemodynamic properties of the aorta are affected by the presence of ILT in patients with AAA that is not explained by aortic size. Alternatively, these findings could be explained by associations between ILT and properties...

  15. Plasma cytokine levels and risks of abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Liao, Mengyang; Liu, Cong-Lin; Lv, Bing-Jie

    2015-01-01

    BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. METHODS AND RESULTS: ELISA determined plasma interleukin-6 (IL6......), IL10, IL17A, IFN-γ, and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients had lower IL6, IFN-γ, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-γ, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively...... with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross...

  16. Modelos de Composição e Percepção de Xenakis: Concret PH e o Pavilhão Philips

    Directory of Open Access Journals (Sweden)

    Danilo Rossetti

    2012-05-01

    Full Text Available Este artigo aborda os modelos de composição e percepção de Xenakis. Segundo o próprio compositor, seu modelo de composição é baseado em distintas formalizações iniciais (estruturas fora-do-tempo, cujo objetivo é gerar dados musicais (estruturas no-tempo, tendo muitas vezes como referência o novo paradigma da ciência moderna do século XX. Por outro lado, a questão da sensibilidade musical é abordada por Xenakis a partir de um viés fundamentado na fenomenologia. Para ilustrar esta dualidade em seu processo criativo, abordaremos analiticamente o processo composicional de sua obra eletroacústica Concret PH (1958 e sua difusão no interior do Pavilhão Philips, cuja concepção de espacialidade se dá a partir do conceito de “gesto eletrônico”. Para a discussão teórica sobre seu modelo perceptivo, trazemos algumas considerações sobre espaço e tempo originárias de Kant e Merleau-Ponty. Já para a análise de Concret PH, nos reportaremos ao modelo de representação sonora de Gabor e ao conceito de trama de Xenakis, além de análises espectrais.

  17. Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.

    Science.gov (United States)

    Schaffer, Caroline Brunsman

    2008-01-01

    Instruction in animal-assisted therapy (AAT) and animal-assisted activities (AAAs) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/AAA also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/AAA are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/AAA programs. This article presents AAT/AAA terminology, ways in which veterinarians can advocate for AAT/AAA, the advantages of being involved in AAT/AAA, a model AAT/AAA practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/AAA by TUSVM's student volunteers.

  18. Preemiad said Rein Raud, fs, Mart Kivastik

    Index Scriptorium Estoniae

    2005-01-01

    Eesti Kultuurkapitali 2004. aasta kirjanduse aastapreemia laureaadid on: Rein Raud ("Hector ja Bernard"), fs (luulekogu "2004"), Mart Kivastik (näidend "Külmetava kunstniku portree"), Jaan Rannap ("Nelja nimega koer"), Toomas Haug ("Troojamäe tõotus"), Harald Rajamets (tõlkeluule kogumik "Pegasos ja peegel"), Antoine Chalvin ("Kalevipoja" tõlge prantsuse keelde"), Ilmar Talve ("Eesti kultuurilugu"), Lauri Sommer (artikkel Uku Masingu käsikirja "Saadik Magellani pilvest" vaimne, ajalis-ruumiline ja elulooline taust), Boris Tuch ("Gorjatshaja desjatka estonskihh pisatelei")

  19. Condition Assessment for Wastewater Pipes: Method for Assessing Cracking and Surface Damage of Concrete Pipes

    OpenAIRE

    Hauge, Petter

    2013-01-01

    The objective of the Master Thesis has been to provide an improved method for condition assessment, which will give a better correlation between Condition class and actual Condition of concrete pipes with cracking and/or surface damages. Additionally improvement of the characterization of cracking (SR) and surface (KO) damages was a sub goal.Based on the findings described in my Thesis and my Specialization Project (Hauge 2012), I recommend that the Norwegian condition assessment method based...

  20. KURVA PHILLIPS DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Maichal Maichal

    2012-12-01

    Full Text Available This paper aims to analyze the existence of the Philips curve in the Indonesian economy, 2000Q1-2010Q3. The results obtained by using OLS method shows that the expectations augmented Philips curve and the New Keynesian Philips curve models cannot give a clear results of Philips curve existence in the Idonesia economy. Shocks variable such as percentage change of exchange rates and crude oil prices provide a very small effect on the inflation rate in Indonesia. Furthermore, the results obtained by using GMM method on the hybrid model of the New Keynesian Philips curve shows that the Philips curve exists in the Indonesian economy.

  1. Vitamins and abdominal aortic aneurysm.

    Science.gov (United States)

    Takagi, Hisato; Umemoto, Takuya

    2017-02-01

    To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E

  2. Abdominal aortic aneurysm screening program in Poland.

    Science.gov (United States)

    Jawien, A; Formankiewicz, B; Derezinski, T; Migdalski, A; Brazis, P; Woda, L

    Screening for abdominal aortic aneurysms (AAA) is currently recommended by several vascular societies. In countries where it has been introduced the prevalence of AAAs differed greatly and was mainly related to cigarette smoking. The screening program also had an enormous impact on the decrease of AAA ruptures and reduced mortality rate. These facts have led to the introduction of the first screening program for AAAs in Poland. The aim of the study was to determine the prevalence of AAAs among men aged 60 years and older undergoing ultrasound examination of the abdominal aorta. A single ultrasonography of the abdomen was performed to assess the aorta from the renal arteries to the bifurcation and the diameter of the aorta was measured at its widest point. The cut-off value for determining an aortic aneurysm was set at a diameter of ≥ 30 mm. All ultrasonography measurements were performed by physicians in outpatient departments throughout the Kuyavian-Pomeranian Province. Additionally, each subject had to fill out a questionnaire with demographic data, smoking habits, existing comorbidities and familial occurrence of AAAs. The study was conducted from October 2009 to November 2011. The abdominal aorta ultrasound examinations were carried out in 1556 men aged 60 years and older. The prevalence of AAA in the study population was 6.0 % (94 out of 1556). The average age of the men was 69 years (SD 6 years, range 60-92 years). In the study population 55 % of the men smoked or had smoked and 3 % were aware of the presence of AAAs in family members. There were three risk factors significantly associated with the presence of AAAs: age (p < 0.05), smoking (72.3 % vs 53.9 %, p = 0.004) and family history of AAAs (9.6 % vs 2.7 %, p = 0.017). The prevalence of AAAs among men in Poland is higher than in other European countries and the USA. The screening program for AAAs is an easy and reliable method for detecting early stages of the disease and

  3. CT diagnosis of ruptured abdominal aortic aneurysm

    International Nuclear Information System (INIS)

    Sacknoff, R.; Novelline, R.A.; Wittenberg, J.; Waltman, A.C.; De Luca, S.A.; Rhea, J.T.; Lawrason, J.N.

    1986-01-01

    Ruptured abdominal aortic aneurysm (AAA) is a life-threatening condition requiring immediate diagnosis and surgery. In a series of 23 consecutive patients scanned by CT for suspected ruptured AAA, CT proved 100% accurate. In seven patients with surgically or pathologically proved ruptured AAA, CT demonstrated a similar distribution of hemorrhage into the perirenal space and to a lesser degree into the anterior and posterior pararenal spaces. The 16 true-negative examinations included ten in patients with unruptured AAA and six in patients with other diseases. The authors conclude that patients in stable condition with suspected ruptured AAA should be examined by CT

  4. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Rubio-Navarro, Alfonso; Amaro Villalobos, Juan Manuel; Lindholt, Jes S

    2015-01-01

    BACKGROUND: Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD......163 expressing macrophages ex vivo, in vitro and in human AAA. METHODS AND RESULTS: CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent...

  5. Patients’ perceptions of conservative treatment for a small abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Tomee SM

    2018-01-01

    Full Text Available Stephanie M Tomee,1 Winifred A Gebhardt,2 Jean-Paul PM de Vries,3 Victoria C Hamelinck,1 Jaap F Hamming,1 Jan HN Lindeman1 1Department of Surgery, Leiden University Medical Center, Leiden, 2Health, Medical and Neuropsychology Unit, Institute of Psychology, Leiden University, Leiden, 3Department of Vascular Surgery, St Antonius Hospital, Nieuwegein, Leiden, the Netherlands Background: An abdominal aortic aneurysm (AAA is a progressive, generally symptomless disease that could ultimately result in a fatal rupture. Current guidelines advise conservative follow-up, and preventive surgical repair once the risk of rupture outweighs the cost of repair (55 mm in men. In developed countries, the majority of patients are diagnosed with AAAs less than 55 mm, and so enter a period of conservative surveillance. An important question is how patients perceive and cope with risk of rupture, AAA diagnosis and treatment, and presented AAA information. The goal of this study was to gain insight into patients’ perceptions of conservative treatment for a small AAA to increase patient satisfaction.Methods: We conducted semistructured in-depth interviews and used questionnaires measuring health-related quality of life (RAND 36-Item Health Survey 1.0, illness-perceptions (Illness Perception Questionnaire – Revised, and anxiety and depression (Hospital Anxiety and Depression Scale. Interviews were audio recorded and transcript contents were analyzed based on grounded theory. Mean scores of the questionnaires were compared to (population reference groups.Results: This study included ten male patients under surveillance for a small AAA from two hospitals in the Netherlands. Patients expressed no fear for AAA rupture, and also reported low levels of anxiety and depression in both the interviews and the Hospital Anxiety and Depression Scale. The presence of an AAA did not affect their social life or emotional well-being. The reported poorer physical health on RAND 36

  6. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

    Lindholt, J S; Juul, Svend; Henneberg, E W

    1997-01-01

    rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...... on uncertain assumptions concerning prevalence, incidence and risk of rupture. Therefore a randomized trial screening of 65-73 year old males is taking place in the County of Viborg in Denmark. Udgivelsesdato: 1997-Mar-24...

  7. In response to an open invitation for comments on AAAS project 2061's Benchmark books on science. Part 1: documentation of serious errors in cell biology.

    Science.gov (United States)

    Ling, Gilbert

    2006-01-01

    Project 2061 was founded by the American Association for the Advancement of Science (AAAS) to improve secondary school science education. An in-depth study of ten 9 to 12th grade biology textbooks led to the verdict that none conveyed "Big Ideas" that would give coherence and meaning to the profusion of lavishly illustrated isolated details. However, neither the Project report itself nor the Benchmark books put out earlier by the Project carries what deserves the designation of "Big Ideas." Worse, in the two earliest-published Benchmark books, the basic unit of all life forms--the living cell--is described as a soup enclosed by a cell membrane, that determines what can enter or leave the cell. This is astonishing since extensive experimental evidence has unequivocally disproved this idea 60 years ago. A "new" version of the membrane theory brought in to replace the discredited (sieve) version is the pump model--currently taught as established truth in all high-school and college biology textbooks--was also unequivocally disproved 40 years ago. This comment is written partly in response to Bechmark's gracious open invitation for ideas to improve the books and through them, to improve US secondary school science education.

  8. Clinical Efficacy of Transthoracic Echocardiography for Screening Abdominal Aortic Aneurysm in Turkish Patients.

    Science.gov (United States)

    Kilic, Salih; Saracoglu, Erhan; Cekici, Yusuf

    2018-03-01

    The objective of this study was to investigate the prevalence of abdominal aortic aneurysm (AAA) in Turkish patients aged ≥ 65 years, and to demonstrate the applicability of echocardiography to AAA screening. Transthoracic echocardiography (TTE) was performed in all consecutive patients aged ≥ 65 years who were referred to cardiology clinics or were referred from other outpatient clinics. The abdominal aorta (AA) of each patient was scanned using the same probe, and the time spent was recorded. Demographic and clinic characteristics of the patients were recorded at the end of the echocardiography. Among 1948 patients (mean age 70.9 ± 6 years; 49.8% male), the AA was visualized in 96.3%. AAA was identified in 3.7% (69/1878) of the patients, of whom AAA was previously known in 20.3% (n = 14). The prevalence of unknown AAA was 2.93%. The average time needed to scan and measure the AA was 1 minute and 3 seconds (±23 seconds). Aortic root diameters were significantly higher in the patients with AAA than in those without AAA (34.7 ± 4.2 vs. 29.8 ± 4.7; p < 0.001). Age (per 1 year increase) [odds ratio (OR), 1.245; p < 0.001], male gender (OR, 5.382; p < 0.001), smoking (OR, 2.118; p = 0.037), and aortic root diameter (per 1 mm increase) (OR, 1.299; p < 0.001) were independent predictors of AAA. This study is important in that it showed a high prevalence of AAA in Turkish patients aged ≥ 65 years, and demonstrated that AAA can be visualized in the majority of patients in as little as 1 minute during TTE.

  9. Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification

    International Nuclear Information System (INIS)

    Bragg, Christopher M.; Wingate, Katrina; Conway, John

    2008-01-01

    Purpose: To determine the implications of the use of the Anisotropic Analytical Algorithm (AAA) for the production and dosimetric verification of IMRT plans for treatments of the prostate, parotid, nasopharynx and lung. Methods: 72 IMRT treatment plans produced using the Pencil Beam Convolution (PBC) algorithm were recalculated using the AAA and the dose distributions compared. Twenty-four of the plans were delivered to inhomogeneous phantoms and verification measurements made using a pinpoint ionisation chamber. The agreement between the AAA and measurement was determined. Results: Small differences were seen in the prostate plans, with the AAA predicting slightly lower minimum PTV doses. In the parotid plans, there were small increases in the lens and contralateral parotid doses while the nasopharyngeal plans revealed a reduction in the volume of the PTV covered by the 95% isodose (the V 95% ) when the AAA was used. Large changes were seen in the lung plans, the AAA predicting reductions in the minimum PTV dose and large reductions in the V 95% . The AAA also predicted small increases in the mean dose to the normal lung and the V 20 . In the verification measurements, all AAA calculations were within 3% or 3.5 mm distance to agreement of the measured doses. Conclusions: The AAA should be used in preference to the PBC algorithm for treatments involving low density tissue but this may necessitate re-evaluation of plan acceptability criteria. Improvements to the Multi-Resolution Dose Calculation algorithm used in the inverse planning are required to reduce the convergence error in the presence of lung tissue. There was excellent agreement between the AAA and verification measurements for all sites

  10. Association between osteopontin and human abdominal aortic aneurysm.

    Science.gov (United States)

    Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

    2007-03-01

    In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

  11. Epidemiology and contemporary management of abdominal aortic aneurysms.

    Science.gov (United States)

    Ullery, Brant W; Hallett, Richard L; Fleischmann, Dominik

    2018-05-01

    Abdominal aortic aneurysm (AAA) is most commonly defined as a maximal diameter of the abdominal aorta in excess of 3 cm in either anterior-posterior or transverse planes or, alternatively, as a focal dilation ≥ 1.5 times the diameter of the normal adjacent arterial segment. Risk factors for the development of AAA include age > 60, tobacco use, male gender, Caucasian race, and family history of AAA. Aneurysm growth and rupture risk appear to be associated with persistent tobacco use, female gender, and chronic pulmonary disease. The majority of AAAs are asymptomatic and detected incidentally on various imaging studies, including abdominal ultrasound, and computed tomographic angiography. Symptoms associated with AAA may include abdominal or back pain, thromboembolization, atheroembolization, aortic rupture, or development of an arteriovenous or aortoenteric fistula. The Screening Abdominal Aortic Aneurysms Efficiently (SAAAVE) Act provides coverage for a one-time screening abdominal ultrasound at age 65 for men who have smoked at least 100 cigarettes and women who have family history of AAA disease. Medical management is recommended for asymptomatic patients with AAAs  5 mm/6 months), or presence of a fusiform aneurysm with maximum diameter of 5.5 cm or greater. Intervention for AAA includes conventional open surgical repair and endovascular aortic stent graft repair.

  12. Iliacaaneurismer sammenlignet med abdominale aortaaneurismer

    DEFF Research Database (Denmark)

    Vammen, S; Henneberg, E W; Fasting, H

    2000-01-01

    aneurysms in the county of Viborg in Denmark 1989-1997. Four thousand one hundred and seventy-six attended screening. One hundred and seventy (4.0%) had an AAA. Twenty-one (0.56%) required operation, while the prevalence of operation-requiring iliac aneurysm (IA) was 0.17%. The operative incidence of IA...... was 18.4 per mill. per year, and 92.4 per mill. per year were operated for AAA. Patients with IA had lower cholesterol-levels, and urological symptoms were present in 42% of cases with isolated IA, and 25% of combined aneurysms compared to 8% of isolated AAA (p ... of the isolated IAs were ruptured, while only 27% of AAAs were ruptured (p IA, 47% in ruptured combined aneurysms, and 31% in ruptured isolated AAA (p IA seems to be more under-diagnosed than AAA, and are often diagnosed because...

  13. Iliacaaneurismer sammenlignet med abdominale aortaaneurismer

    DEFF Research Database (Denmark)

    Vammen, Sten; Henneberg, E W; Fasting, H

    2000-01-01

    aneurysms in the county of Viborg in Denmark 1989-1997. Four thousand one hundred and seventy-six attended screening. One hundred and seventy (4.0%) had an AAA. Twenty-one (0.56%) required operation, while the prevalence of operation-requiring iliac aneurysm (IA) was 0.17%. The operative incidence of IA...... was 18.4 per mill. per year, and 92.4 per mill. per year were operated for AAA. Patients with IA had lower cholesterol-levels, and urological symptoms were present in 42% of cases with isolated IA, and 25% of combined aneurysms compared to 8% of isolated AAA (p ... IAs were ruptured, while only 27% of AAAs were ruptured (p IA, 47% in ruptured combined aneurysms, and 31% in ruptured isolated AAA (p IA seems to be more under-diagnosed than AAA, and are often diagnosed because...

  14. Science | AAAS

    Science.gov (United States)

    Giuseppe Conte Italy's new prime minister defended discredited stem cell therapy By Luca Tancredi Barone defended discredited stem cell therapy By Luca Tancredi Barone May. 24, 2018 illustration of GOES-17 | May. 24, 2018 STEPHAN JUNEK/MPI BRAIN RESEARCH Apparatus for building a single NaCs molecule from two

  15. Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. AAA group, cv. Cavendish).

    Science.gov (United States)

    Wang, Zhuo; Huang, Suzhen; Jia, Caihong; Liu, Juhua; Zhang, Jianbin; Xu, Biyu; Jin, Zhiqiang

    2013-09-01

    Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. AAA group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.

  16. NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikatsu, Yuki [Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Ishida, Yo-ichi; Sudo, Haruka [Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Yuasa, Keizo; Tsuji, Akihiko [Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp [Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan)

    2015-08-28

    Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosome complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex. - Highlights: • ATPase-deficient mutants of NVL2 have decreased pre-rRNA processing. • NVL2 associates with the nuclear exosome through interactions with MTR4 and RRP6. • MPP6 stabilizes MTR4-RRP6 interaction and allows NVL2 to interact with the complex.

  17. Screening of COPD patients for abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Flessenkaemper IH

    2015-06-01

    Full Text Available Ingo H Flessenkaemper,1 Robert Loddenkemper,2 Stephanie Roll,3 Kathrin Enke-Melzer,1 Henrik Wurps,2 Torsten T Bauer21Department for Vascular Medicine, 2Department of Pneumology, Helios Klinikum Emil von Behring, Berlin, Germany; 3Institute for Social Medicine, Epidemiology and Health Economics, Charité – Universitätsmedizin Berlin, Berlin, GermanyPurpose: Screening for abdominal aortic aneurysm (AAA in “men aged over 65 years who have ever smoked” is a recommended policy. To reduce the number of screenings, it may be of value to define subgroups with a higher prevalence of AAA. Since chronic obstructive pulmonary disease (COPD and AAA are associated with several common risk factors, this study investigates the prevalence of AAA in COPD patients.Patients and methods: Patients with COPD were identified via the hospital information system. Inclusion criteria were: COPD stage I–IV, ability to give full consent, and age >18 years; exclusion criteria were: patient too obese for an ultrasound check, previously diagnosed AAA, prior surgery for AAA, or ethical grounds such as concomitant advanced malignant or end-stage disease. The primary endpoint of the study was an aortic diameter measured by ultrasound of ≥30 mm. Defined secondary endpoints were evaluated on the basis of medical records and interviews.Results: Of the 1,180 identified COPD patients, 589 were included in this prospective study. In 22 patients (3.70%, the aortic diameter was ≥30 mm, representing an AAA prevalence of 6.72% among males aged >65 years. The risk of AAA increased with the following comorbidities/risk factors: male sex (odds ratio [OR] 2.98, coronary heart disease (OR 2.81, peripheral arterial occlusive disease (OR 2.47, hyperlipoproteinemia (OR 2.77, AAA in the family history (OR 3.95, and COPD stage I/II versus IV (OR 1.81.Conclusion: The overall AAA prevalence of 3.7% in our group of COPD patients is similar to that of the general population aged >65

  18. Myeloperoxidase-mediated protein lysine oxidation generates 2-aminoadipic acid and lysine nitrile in vivo.

    Science.gov (United States)

    Lin, Hongqiao; Levison, Bruce S; Buffa, Jennifer A; Huang, Ying; Fu, Xiaoming; Wang, Zeneng; Gogonea, Valentin; DiDonato, Joseph A; Hazen, Stanley L

    2017-03-01

    Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2-AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or base-catalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate protein-bound 2-AAA from an alternative potential lysine oxidative product, lysine nitrile (LysCN). Using a validated protease-based digestion method coupled with stable isotope dilution LC/MS/MS, we now report protein bound 2-AAA and LysCN are both formed by hypochlorous acid (HOCl) and the MPO/H 2 O 2 /Cl - system of leukocytes. At low molar ratio of oxidant to target protein N ε -lysine moiety, 2-AAA is formed via an initial N ε -monochloramine intermediate, which ultimately produces the more stable 2-AAA end-product via sequential generation of transient imine and semialdehyde intermediates. At higher oxidant to target protein N ε -lysine amine ratios, protein-bound LysCN is formed via initial generation of a lysine N ε -dichloramine intermediate. In studies employing MPO knockout mice and an acute inflammation model, we show that both free and protein-bound 2-AAA, and in lower yield, protein-bound LysCN, are formed by MPO in vivo during inflammation. Finally, both 2-AAA and to lesser extent LysCN are shown to be enriched in human aortic atherosclerotic plaque, a tissue known to harbor multiple MPO-catalyzed protein oxidation products. Collectively, these results show that MPO-mediated oxidation of protein lysyl

  19. Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.

    Science.gov (United States)

    Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude

    2018-01-01

    Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the AAA, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the AAA lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific AAA during disease progression

  20. The impact of endovascular repair on specialties performing abdominal aortic aneurysm repair

    NARCIS (Netherlands)

    Ultee, Klaas H J; Hurks, Rob; Buck, Dominique B.; Dasilva, George S.; Soden, Peter A.; Van Herwaarden, Joost A.; Verhagen, Hence J M; Schermerhorn, Marc L.

    2015-01-01

    Background Abdominal aortic aneurysm (AAA) repair has been performed by various surgical specialties for many years. Endovascular aneurysm repair (EVAR) may be a disruptive technology, having an impact on which specialties care for patients with AAA. Therefore, we examined the proportion of AAA

  1. Screening for abdominal aortic aneurysm reduces overall mortality in men. A meta-analysis of the mid- and long-term effects of screening for abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Norman, P

    2008-01-01

    Four randomised controlled trials of screening older men for abdominal aortic aneurysms (AAA) have been completed. A meta-analysis was performed to examine the pooled effects of screening on both mid- and long-term AAA-related and total mortality, and operations for AAA....

  2. Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

    Science.gov (United States)

    Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E

    2008-01-01

    Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

  3. No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder

    OpenAIRE

    Bergwerff, C.E.; Luman, M.; Blom, H.J.; Oosterlaan, J.

    2016-01-01

    Background The aim of the current study was to explore the role of aromatic amino acids (AAAs) in blood in relation to attention-deficit/hyperactivity disorder (ADHD). Given their impact on the synthesis of serotonin and dopamine, decreased concentrations of the AAAs tryptophan, tyrosine and phenylalanine in blood may contribute to the expression of ADHD symptoms. Decreased AAA blood concentrations, in turn, may be related to lowered dietary protein intake or to abnormal AAA catabolism, as ev...

  4. Memories of Future Masculine Identities: A Comparison of Philip K. Dick’s “We Can Remember it for you Wholesale”, the 1990 Film Total Recall and its 2012 Remake

    Directory of Open Access Journals (Sweden)

    Amaya Fernández-Menicucci

    2014-12-01

    Full Text Available Recent remakes of iconic science fiction films such as Total Recall, far from merely reproducing cultural landscapes from the past, are actively producing new constructions of categories of identity such as gender and sexuality. In particular, in the two filmic adaptations of Philip K. Dick’s short story “We Can Remember it for you Wholesale” by Paul Verhoeven in 1990 and Len Wiseman in 2012, memory is a metaphor for the historical accountability of hegemonic masculinity—or the lack thereof. Dick’s original text and both Total Recall adaptations can be read as revisionist approaches to the past through a dystopian vision of the future, which, in turn, is but a projection of present anxieties of masculinities in crisis. A comparative analysis of the amnesiac heroes presented in these three sci-fi texts will thus offer an insight into the way in which futuristic action men ‘recall’ present and past discourses on power. Indeed, memory constitutes the narrative mechanism that allows collective and individual realities to be questioned and re-imagined through the intra-textual and inter-textual references present in the three texts in question.

  5. Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.

    Science.gov (United States)

    Yerly, Patrick; Madeleine, George; Riesen, Walter; Bovet, Pascal

    2013-03-01

    The prevalence of abdominal aortic aneurysm (AAA) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on AAA in the African region. We evaluated the prevalence of AAA in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of AAA was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of AAA in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of AAA, such as smoking (in men), high blood pressure and hypercholesterolaemia.

  6. Plasma cathepsin S and cystatin C levels and risk of abdominal aortic aneurysm: a randomized population-based study.

    Directory of Open Access Journals (Sweden)

    Bing-Jie Lv

    Full Text Available BACKGROUND: Human abdominal aortic aneurysm (AAA lesions contain high levels of cathepsin S (CatS, but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown. METHODS AND RESULTS: Plasma samples were collected from 476 male AAA patients and 200 age-matched male controls to determine CatS and cystatin C levels by ELISA. Student's t test demonstrated higher plasma levels of total, active, and pro-CatS in AAA patients than in controls (P<0.001. ROC curve analysis confirmed higher plasma total, active, and pro-CatS levels in AAA patients than in controls (P<0.001. Logistic regression suggested that plasma total (odds ratio [OR] = 1.332, active (OR = 1.21, and pro-CatS (OR = 1.25 levels were independent AAA risk factors that associated positively with AAA (P<0.001. Plasma cystatin C levels associated significantly, but negatively, with AAA (OR = 0.356, P<0.001. Univariate correlation demonstrated that plasma total and active CatS levels correlated positively with body-mass index, diastolic blood pressure, and aortic diameter, but negatively with the lowest ankle-brachial index (ABI. Plasma cystatin C levels also correlated negatively with the lowest ABI. Multivariate linear regression showed that plasma total, active, and pro-CatS levels correlated positively with aortic diameter and negatively with the lowest ABI, whereas plasma cystatin C levels correlated negatively with aortic diameter and the lowest ABI, after adjusting for common AAA risk factors. CONCLUSIONS: Correlation of plasma CatS and cystatin C with aortic diameter and the lowest ABI suggest these serological parameters as biomarkers for human peripheral arterial diseases and AAA.

  7. Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

    Science.gov (United States)

    Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

    2017-06-01

    Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular

  8. The prevalence of abdominal aortic aneurysms in the rural/urban population in central Poland - Gniewkowo Aortic Study.

    Science.gov (United States)

    Dereziński, Tadeusz L; Fórmankiewicz, Bartosz; Migdalski, Arkadiusz; Brazis, Paweł; Jakubowski, Grzegorz; Woda, Łukasz; Jawień, Arkadiusz

    2017-01-01

    Abdominal aortic aneurysm (AAA) is a widening of the aorta below the renal arteries with a diameter equal to or greater than 3 cm. The prevalence of AAA is estimated at 4-8% in men aged 65 years or older and 1-2% among women over 65 years old. Participation in screening programmes has decreased the number of aortic ruptures. All men aged 60 years and older, and women aged 65 years and older living in the rural/urban commune in central Poland were invited to participate in the study. In total 922 persons (61% of the invited population) entered the study. The men were divided into two groups: 60-64 years old, and 65 years and older. Screening abdomen ultrasound was performed and demographic data was collected. Among the 922 examined persons two (1.01%) AAAs were diagnosed in the group of men 60-64 years of age, three (0.82%) AAAs amongst women ≥ 65 years old, and 33 (9.29%) AAAs were found in the group of men aged 65 years and older. A positive relationship between the presence of AAA and smoking (p = 0.0048), age of men (p = 0.0009), and history of myocardial infarction/acute coronary syndrome (MI/ACS) (p = 0.0079) was found. There was no correlation between the frequency of AAA and diabetes mellitus (p = 0.46), hypertension (p = 0.38), and family history of AAA (p = 0.44). The prevalence of AAA in men aged 65 years and older is seemingly larger than in previously conducted studies, while among men 60-64 years of age and women aged ≥ 65 it is similar. Older age, smoking, and a history of MI/ACS were the most important risk factors of AAA occurrence.

  9. Vessel asymmetry as an additional diagnostic tool in the assessment of abdominal aortic aneurysms.

    LENUS (Irish Health Repository)

    Doyle, Barry J

    2009-02-01

    OBJECTIVE: Abdominal aortic aneurysm (AAA) rupture is believed to occur when the local mechanical stress exceeds the local mechanical strength of the wall tissue. On the basis of this hypothesis, the knowledge of the stress acting on the wall of an unruptured aneurysm could be useful in determining the risk of rupture. The role of asymmetry has previously been identified in idealized AAA models and is now studied using realistic AAAs in the current work. METHODS: Fifteen patient-specific AAAs were studied to estimate the relationship between wall stress and geometrical parameters. Three-dimensional AAA models were reconstructed from computed tomography scan data. The stress distribution on the AAA wall was evaluated by the finite element method, and peak wall stress was compared with both diameter and centerline asymmetry. A simple method of determining asymmetry was adapted and developed. Statistical analyses were performed to determine potential significance of results. RESULTS: Mean von Mises peak wall stress +\\/- standard deviation was 0.4505 +\\/- 0.14 MPa (range, 0.3157-0.9048 MPa). Posterior wall stress increases with anterior centerline asymmetry. Peak stress increased by 48% and posterior wall stress by 38% when asymmetry was introduced into a realistic AAA model. CONCLUSION: The relationship between posterior wall stress and AAA asymmetry showed that excessive bulging of one surface results in elevated wall stress on the opposite surface. Assessing the degree of bulging and asymmetry that is experienced in an individual AAA may be of benefit to surgeons in the decision-making process and may provide a useful adjunct to diameter as a surgical intervention guide.

  10. Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

    Science.gov (United States)

    Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

    2017-01-01

    Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.

    Science.gov (United States)

    Ahmad, Mehtab; Kuravi, Sahithi; Hodson, James; Rainger, G Ed; Nash, Gerard B; Vohra, Rajiv K; Bradbury, Andrew W

    2018-02-16

    In a pilot study, a relationship between abdominal aortic aneurysm (AAA) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation in vitro in response to serum from patients with AAA was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal AAA size, morphology, and growth rates. Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal AAA and related to aneurysm size, morphology, and growth rates. IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26 pg/mL. There was no statistically significant relationship between IL-1α and maximum AAA antero-posterior diameter as measured by ultrasound (p = .649), AAA morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p = .629]) as measured on computed tomography, absolute increase in AAA diameter (p = .214), or AAA growth rate (p = .230). IL-1α is detectable in the majority of patients with infrarenal AAA, but the cause and clinical significance of this novel observation remains unknown. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  12. From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Martinez-Pinna, Roxanna; Lindholt, Jes Sanddal; Madrigal-Matute, Julio

    2014-01-01

    Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red bloo...

  13. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, G.T.; Tromp, G.; Kuivaniemi, H.; Gretarsdottir, S.; Baas, A.F.; Giusti, B.; Strauss, E.; Hof, F.N. van 't; Webb, T.R.; Erdman, R.; Ritchie, M.D.; Elmore, J.R.; Verma, A.; Pendergrass, S.; Kullo, I.J.; Ye, Z.; Peissig, P.L.; Gottesman, O.; Verma, S.S.; Malinowski, J.; Rasmussen-Torvik, L.J.; Borthwick, K.M.; Smelser, D.T.; Crosslin, D.R.; Andrade, M. de; Ryer, E.J.; McCarty, C.A.; Bottinger, E.P.; Pacheco, J.A.; Crawford, D.C.; Carrell, D.S.; Gerhard, G.S.; Franklin, D.P.; Carey, D.J.; Phillips, V.L.; Williams, M.J.; Wei, W.; Blair, R.; Hill, A.A.; Vasudevan, T.M.; Lewis, D.R.; Thomson, I.A.; Krysa, J.; Hill, G.B.; Roake, J.; Merriman, T.R.; Oszkinis, G.; Galora, S.; Saracini, C.; Abbate, R.; Pulli, R.; Pratesi, C.; Saratzis, A.; Verissimo, A.R.; Bumpstead, S.; Badger, S.A.; Clough, R.E.; Cockerill, G.; Hafez, H.; Scott, D.J.; Futers, T.S.; Romaine, S.P.; Bridge, K.; Griffin, K.J.; Bailey, M.A.; Smith, A.; Thompson, M.M.; Bockxmeer, F.M. van; Matthiasson, S.E.; Thorleifsson, G.; Thorsteinsdottir, U.; Blankensteijn, J.D.; Teijink, J.A.; Wijmenga, C.; Graaf, J. de; Kiemeney, L.A.L.M.; Lindholt, J.S.; Hughes, A.; Bradley, D.T.; Stirrups, K.; Golledge, J.; Norman, P.E.; Powell, J.T.; Humphries, S.E.; Hamby, S.E.; Goodall, A.H.; Nelson, C.P.; Sakalihasan, N.; Courtois, A.; Ferrell, R.E.; Eriksson, P.; Folkersen, L.; Franco-Cereceda, A.; Eicher, J.D.; Johnson, A.D.; Betsholtz, C.; Ruusalepp, A.; Franzen, O.; Schadt, E.E.; Bjorkegren, J.L.; et al.,

    2017-01-01

    RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available

  14. Lack of association between inguinal hernia and abdominal aortic aneurysm in a population-based male cohort

    DEFF Research Database (Denmark)

    Henriksen, N A; Sorensen, L T; Jorgensen, L N

    2013-01-01

    Previous studies have reported a higher prevalence of inguinal hernia in patients with abdominal aortic aneurysm (AAA). The aim of this study was to explore the association between inguinal hernia and AAA in a large population-based cohort of men who had screening for AAA....

  15. AAA+ ATPases Reptin and Pontin as potential diagnostic and prognostic biomarkers in salivary gland cancer - a short report.

    Science.gov (United States)

    Mikesch, Jan-Henrik; Hartmann, Wolfgang; Angenendt, Linus; Huber, Otmar; Schliemann, Christoph; Arteaga, Maria Francisca; Wardelmann, Eva; Rudack, Claudia; Berdel, Wolfgang E; Stenner, Markus; Grünewald, Inga

    2018-06-05

    Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metastasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse tumors. In recent years, the AAA+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are frequently deregulated in cancer. The aim of this study was to assess the clinical and functional significance of Reptin and Pontin expression in SGC. Immunohistochemical staining of Pontin, Reptin, β-catenin, Cyclin D1, TP53 and MIB-1 was performed on a collection of 94 SGC tumor samples comprising 13 different histological subtypes using tissue microarrays. We found that Reptin and Pontin were expressed in the majority of SGC samples across all histological subtypes. Patients with a high Reptin expression showed a significantly inferior 5-year overall survival rate compared to patients with a low Reptin expression (47.7% versus 78.3%; p = 0.033), whereas no such difference was observed for Pontin. A high Reptin expression strongly correlated with a high expression of the proliferation marker MIB-1 (p = 0.003), the cell cycle regulator Cyclin D1 (p = 0.006), accumulation of TP53 as a surrogate p53 mutation marker (p = 0.042) and cytoplasmic β-catenin expression (p = 0.002). Increased Pontin expression was found to significantly correlate with both cytoplasmic and nuclear β-catenin expression (p = 0.037 and p = 0.018, respectively), which is indicative for its oncogenic function. Our results suggest a role of Reptin and Pontin in SGC tumor progression and/or patient survival. Therefore, SGC patients exhibiting a high Reptin expression may benefit from more aggressive therapeutic regimens. Future studies should clarify whether such patients may be considered

  16. Dye-sensitized solar cell based on AZO/Ag/AZO multilayer transparent conductive oxide film

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Jin-He; Li, Ying [School of Materials Science and Engineering, Shanghai University, 149 Yanchang Road, Shanghai 200072 (China); Duong, Thanh-Tung; Choi, Hyung-Jin [Department of Materials Engineering, Chungnam National University, Daeduk Science Town, 305-764 Daejeon (Korea, Republic of); Yoon, Soon-Gil, E-mail: sgyoon@cnu.ac.kr [Department of Materials Engineering, Chungnam National University, Daeduk Science Town, 305-764 Daejeon (Korea, Republic of)

    2013-04-15

    Highlights: ► AZO/Ag/AZO (AAA) multilayer was used for working electrode of DSSC cell. ► The 100 nm-thick Nb-doped TiO{sub 2} layer showed a good blocking effect. ► The DSSC cell by AAA TCO material showed the highest efficiency of about 3.25%. -- Abstract: Niobium-doped TiO{sub 2} blocking layer and Al-doped ZnO (AZO)/Ag/AZO (AAA) TCO layers were grown onto glass substrate using pulsed laser deposition (PLD) and direct current (dc)/radio-frequency (rf) sputtering at room temperature, respectively for dye-sensitized solar cell (DSSC) applications. The 100 nm-thick NTO layer showed a blocking effect for the oxygen diffusion into AAA layer and for the recombination of the electrons. The DSSC cell composed of the NTO (100 nm)/AAA (400 nm) showed the highest photo-electrical efficiency of about 3.25%. An insertion of aluminum foil between serrated clip and AAA (100 nm) TCO improved a photo-conversion efficiency of the DSSC.

  17. IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Wang, Jing; Lindholt, Jes S; Sukhova, Galina K

    2014-01-01

    Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD......8+ T cells. IgE induces CD4+ T-cell production of IL6 and IFN-γ, but reduces their production of IL10. FcεR1 deficiency (Fcer1a-/-) protects apolipoprotein E-deficient (Apoe-/-) mice from angiotensin-II infusion-induced AAAs and reduces plasma IL6 levels. Adoptive transfer of CD4+ T cells (but...... with AAAs had significantly higher plasma IgE levels than those without AAAs. This study establishes an important role of IgE in AAA pathogenesis by activating CD4+ T cells, MCs, and macrophages and supports consideration of neutralizing plasma IgE in the therapeutics of human AAAs....

  18. Dye-sensitized solar cell based on AZO/Ag/AZO multilayer transparent conductive oxide film

    International Nuclear Information System (INIS)

    Qi, Jin-He; Li, Ying; Duong, Thanh-Tung; Choi, Hyung-Jin; Yoon, Soon-Gil

    2013-01-01

    Highlights: ► AZO/Ag/AZO (AAA) multilayer was used for working electrode of DSSC cell. ► The 100 nm-thick Nb-doped TiO 2 layer showed a good blocking effect. ► The DSSC cell by AAA TCO material showed the highest efficiency of about 3.25%. -- Abstract: Niobium-doped TiO 2 blocking layer and Al-doped ZnO (AZO)/Ag/AZO (AAA) TCO layers were grown onto glass substrate using pulsed laser deposition (PLD) and direct current (dc)/radio-frequency (rf) sputtering at room temperature, respectively for dye-sensitized solar cell (DSSC) applications. The 100 nm-thick NTO layer showed a blocking effect for the oxygen diffusion into AAA layer and for the recombination of the electrons. The DSSC cell composed of the NTO (100 nm)/AAA (400 nm) showed the highest photo-electrical efficiency of about 3.25%. An insertion of aluminum foil between serrated clip and AAA (100 nm) TCO improved a photo-conversion efficiency of the DSSC

  19. Clinical implementation and evaluation of the Acuros dose calculation algorithm.

    Science.gov (United States)

    Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

    2017-09-01

    The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and

  20. A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the AAA+ ATPase p97/VCP.

    Science.gov (United States)

    Chimenti, Michael S; Bulfer, Stacie L; Neitz, R Jeffrey; Renslo, Adam R; Jacobson, Matthew P; James, Thomas L; Arkin, Michelle R; Kelly, Mark J S

    2015-07-01

    The ubiquitous AAA+ ATPase p97 functions as a dynamic molecular machine driving several cellular processes. It is essential in regulating protein homeostasis, and it represents a potential drug target for cancer, particularly when there is a greater reliance on the endoplasmic reticulum-associated protein degradation pathway and ubiquitin-proteasome pathway to degrade an overabundance of secreted proteins. Here, we report a case study for using fragment-based ligand design approaches against this large and dynamic hexamer, which has multiple potential binding sites for small molecules. A screen of a fragment library was conducted by surface plasmon resonance (SPR) and followed up by nuclear magnetic resonance (NMR), two complementary biophysical techniques. Virtual screening was also carried out to examine possible binding sites for the experimental hits and evaluate the potential utility of fragment docking for this target. Out of this effort, 13 fragments were discovered that showed reversible binding with affinities between 140 µM and 1 mM, binding stoichiometries of 1:1 or 2:1, and good ligand efficiencies. Structural data for fragment-protein interactions were obtained with residue-specific [U-(2)H] (13)CH3-methyl-labeling NMR strategies, and these data were compared to poses from docking. The combination of virtual screening, SPR, and NMR enabled us to find and validate a number of interesting fragment hits and allowed us to gain an understanding of the structural nature of fragment binding. © 2015 Society for Laboratory Automation and Screening.