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Sample records for ap del proceso

  1. A Failed Utopia in Marcela Del Río's "Proceso a Faubritten"

    ERIC Educational Resources Information Center

    Manickam, Samuel

    2014-01-01

    In Marcela del Río's science fiction novel "Proceso a Faubritten," utopia comes in the form of eternal life for all of humanity, thanks to Dr. Alexander Faubritten's "Bomba L." This polyphonic work includes diaries by Faubritten and his Mexican lover, María Corona. In my analysis of these two diaries, I will show how…

  2. Estudio numerico y experimental del proceso de soldeo MIG sobre la aleacion 6063--T5 utilizando el metodo de Taguchi

    NASA Astrophysics Data System (ADS)

    Meseguer Valdenebro, Jose Luis

    improvement on mechanical properties in aluminum metal joint. Los procesos de soldadura por arco electrico representan unas de las tecnicas mas utilizadas en los procesos de fabricacion de componentes mecanicos en la industria moderna. Los procesos de soldeo por arco se han adaptado a las necesidades actuales, haciendose un modo de fabricacion flexible y versatil. Los resultados obtenidos numericamente en el proceso de soldadura son validados experimentalmente. Los principales metodos numericos mas empleados en la actualidad son tres, metodo por diferencias finitas, metodos por elementos finitos y metodo por volumenes finitos. El metodo numerico mas empleado para el modelado de uniones soldadas, es el metodo por elementos finitos, debido a que presenta una buena adaptacion a las condiciones geometricas y de contorno ademas de que existe una diversidad de programas comerciales que utilizan el metodo por elementos finitos como base de calculo. Este trabajo de investigacion presenta un estudio experimental de una union soldada mediante el proceso MIG de la aleacion de aluminio 6063-T5. El metodo numerico se valida experimentalmente aplicando el metodo de los elementos finitos con el programa de calculo ANSYS. Los resultados experimentales obtenidos son: las curvas de enfriamiento, el tiempo critico de enfriamiento t4/3, geometria del cordon, microdurezas obtenidas en la union soldada, zona afectada termicamente y metal base, dilucion del proceso, areas criticas intersecadas entre las curvas de enfriamiento y la curva TTP. Los resultados numericos son: las curvas del ciclo termico, que representan tanto el calentamiento hasta alcanzar la temperatura maxima y un posterior enfriamiento. Se calculan el tiempo critico de enfriamiento t4/3, el rendimiento termico y se representa la geometria del cordon obtenida experimentalmente. La zona afectada termicamente se obtiene diferenciando las zonas que se encuentran a diferentes temperaturas, las areas criticas intersecadas entre las

  3. La utilizacion de los mapas conceptuales en la ensenanza de biologia y su efecto sobre el dominio del proceso de fotosintesis en los estudiantes universitarios

    NASA Astrophysics Data System (ADS)

    Gonzalez Rivera, Maria M.

    Se investigo el efecto de los mapas conceptuales sobre el dominio del proceso de fotosintesis en estudiantes universitarios. La investigacion utilizo dos estrategias: mapas conceptuales individuales y mapas conceptuales colaborativos, con el fin de investigar si existen diferencias significativas en el dominio del proceso de fotosintesis. El analisis de los datos incluyo aspectos cualitativos y cuantitativos. Se desprende del estudio que el 80% de los estudiantes describen la utilizacion de los mapas conceptuales como una experiencia beneficiosa. El 70% de los estudiantes expreso que los mapas conceptuales son utiles en el aprendizaje del proceso de fotosintesis y el 61% indico que facilitan la comprension de los conceptos. Los hallazgos mas importantes del analisis cuantitativo indican que los estudiantes que utilizaron los mapas conceptuales mejoraron significativamente su desempeno en la posprueba global. Se utilizo la prueba Mann-Whitney para investigar si existian diferencias significativas en la posprueba y preprueba global, el valor de W = 1945.0, para un valor p de 0.00, lo cual establece diferencias significativas. Para determinar si existian diferencias significativas entre la posprueba y preprueba del grupo individual, se realizo la prueba nuevamente. El valor de W correspondio a 490.5, que es significativo, con un valor p de 0.00. Se concluye que existen diferencias significativas entre la ejecucion de la posprueba y preprueba del grupo individual. Los datos proveen suficiente evidencia para sostener que los estudiantes que utilizaron la estrategia de mapas conceptuales individuales mejoraron el dominio del proceso de fotosintesis significativamente. Se realizo nuevamente la prueba para los resultados de posprueba y preprueba del grupo colaborativo. El valor de W correspondio a 446 con un valor p de 0.00. Se concluyo que existen diferencias significativas entre la ejecucion de la posprueba y preprueba del grupo colaborativo. Finalmente, se efectuo una

  4. AP Music Theory Applied

    ERIC Educational Resources Information Center

    Spieker, Matthew H.

    2016-01-01

    Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

  5. PSAT and AP Success.

    ERIC Educational Resources Information Center

    Palin, Raymond J.

    2001-01-01

    Through evaluation of 73 eleventh-grade students over three years, explores the extent to which standardized test scores and other academic factors predict success on the Advanced Placement (AP) exam in U.S. history. Finds that standardized scores, grade point average, and anticipated college majors are closely related to AP success. (CMK)

  6. APS and Open Access

    NASA Astrophysics Data System (ADS)

    2011-03-01

    The movement toward Open Access continues to gain momentum. A brief review of APS efforts in this area will be presented by APS Editor in Chief, Gene Sprouse. Editors from Physical Review A, B, E, Focus, Letters, and X, Reviews of Modern Physics, and Physics will address your questions about publishing in this evolving environment.

  7. APS Science 2006.

    SciTech Connect

    Gibson, J. M.; Fenner, R. B.; Long, G.; Borland, M.; Decker, G.

    2007-05-24

    In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R&D. The ERL{at}APS would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have emerged from

  8. APS Science 2009.

    SciTech Connect

    Gibson, J. M; Mills, D. M.; Gerig, R.

    2010-05-01

    It is my pleasure to introduce the 2009 annual report of the Advanced Photon Source. This was a very good year for us. We operated with high reliability and availability, despite growing problems with obsolete systems, and our users produced a record output of publications. The number of user experiments increased by 14% from 2008 to more than 3600. We congratulate the recipients of the 2009 Nobel Prize in Chemistry-Venkatraman Ramakrishnan (Cambridge Institute for Medical Research), Thomas Steitz (Yale University), and Ada Yonath (Weizmann Institute) - who did a substantial amount of this work at APS beamlines. Thanks to the efforts of our users and staff, and the ongoing counsel of the APS Scientific Advisory Committee, we made major progress in advancing our planning for the upgrade of the APS (APS-U), producing a proposal that was positively reviewed. We hope to get formal approval in 2010 to begin the upgrade. With advocacy from our users and the support of our sponsor, the Office of Basic Energy Sciences in the Department of Energy (DOE) Office of Science, our operating budgets have grown to the level needed to more adequately staff our beamlines. We were also extremely fortunate to have received $7.9 M in American Recovery and Reinvestment Act ('stimulus') funding to acquire new detectors and improve several of our beamlines. The success of the new Linac Coherent Light Source at Stanford, the world's first x-ray free-electron laser, made us particularly proud since the undulators were designed and built by the APS. Among other highlights, we note that more than one-quarter of the 46 Energy Frontier Research Centers, funded competitively across the U.S. in 2009 by the DOE, included the Advanced Photon Source in their proposed work, which shows that synchrotron radiation, and the APS in particular, are central to energy research. While APS research covers everything from fundamental to applied science (reflected by the highlights in this report), the challenge

  9. AP@home

    PubMed Central

    Heinemann, Lutz; Benesch, Carsten; DeVries, J. Hans

    2016-01-01

    In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union–funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 “final studies” during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a “single-port AP system” was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners. PMID:26888971

  10. Liaison to DASN AP

    DTIC Science & Technology

    2014-08-01

    Liaison  to  DASN   AP   Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is...control number. 1. REPORT DATE AUG 2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Liaison to DASN AP 5a...on  was  created:   § To  serve  as  a  liaison  between  the  DON   OSBP  and  DASN   AP   § Co-­‐located  to

  11. Peculiar Traits of Coarse AP

    DTIC Science & Technology

    2014-01-01

    contained ammonium chlorate and some amounts of AP degradation products. Khairetdinov and Boldyrev called small nuclei “seeds or germs”. They observed...grew to larger sizes. Increased concentration of chlorate ion in AP produced a proliferation of germs and decreased induction time before AP LTD...AP LTD reactions were chlorate ion concentration dependent. As chlorate content was increased decomposition reaction rates were greater in the AP

  12. Advancing beyond AP Courses

    ERIC Educational Resources Information Center

    Hammond, Bruce G.

    2009-01-01

    A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

  13. APS Science 2007.

    SciTech Connect

    Not Available

    2008-05-30

    This report provides research highlights from the Advanced Photon Source (APS). Although these highlights represent less than 10% of the published work from the APS in 2007, they give a flavor of the diversity and impact of user research at the facility. In the strategic planning the aim is to foster the growth of existing user communities and foresee new areas of research. This coming year finds the APS engaged in putting together, along with the users, a blueprint for the next five years, and making the case for a set of prioritized investments in beamlines, the accelerator, and infrastructure, each of which will be transformational in terms of scientific impact. As this is written plans are being formulated for an important user workshop on October 20-21, 2008, to prioritize strategic plans. The fruit from past investments can be seen in this report. Examples include the creation of a dedicated beamline for x-ray photon correlation spectroscopy at Sector 8, the evolution of dedicated high-energy x-ray scattering beamlines at sectors 1 and 11, a dedicated imaging beamline at Sector 32, and new beamlines for inelastic scattering and powder diffraction. A single-pulse facility has been built in collaboration with Sector 14 (BioCARS) and Phil Anfinrud at the National Institutes of Health, which will offer exceptionally high flux for single-pulse diffraction. The nanoprobe at Sector 26, built and operated jointly by the Argonne Center for Nanoscale Materials and the X-ray Operations and Research (XOR) section of the APS X-ray Science Division, has come on line to define the state of the art in nanoscience.

  14. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    PubMed

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

  15. Learning about Antiphospholipid Syndrome (APS)

    MedlinePlus

    ... and links from the National Institutes of Health. Learning About Antiphospholipid Syndrome (APS) What is antiphospholipid syndrome ( ... with APS include : Systemic Vascular Thrombosis While the deep veins of the legs are the most frequent ...

  16. Renal involvement in the antiphospholipid syndrome (APS)-APS nephropathy.

    PubMed

    Tektonidou, Maria G

    2009-06-01

    Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

  17. The APS ceramic chambers

    SciTech Connect

    Milton, S.; Warner, D.

    1994-07-01

    Ceramics chambers are used in the Advanced Photon Source (APS) machines at the locations of the pulsed kicker and bumper magnets. The ceramic will be coated internally with a resistive paste. The resistance is chosen to allow the low frequency pulsed magnet field to penetrate but not the high frequency components of the circulating beam. Another design goal was to keep the power density experienced by the resistive coating to a minimum. These ceramics, their associated hardware, the coating process, and our recent experiences with them are described.

  18. Final report for tank 241-AP-101, grab samples 1AP-95-1, 1AP-95-2, 1AP-95-3, 1AP-95-4, 1AP-95-5, and 1AP-95-6

    SciTech Connect

    Esch, R.A.

    1996-03-04

    Six supernate grab samples (1AP-95-1 through 6) and one field blank (1AP-95-7) were taken from tank 241-AP-101, on Nov. 10 and 13, 1995. Analyses were performed in support of the Safety Screening and the Waste Compatibility Safety programs. All analytical results were within the action limits stated in the TSAP.

  19. APS Editorial Q&A: APS and Open Access

    NASA Astrophysics Data System (ADS)

    2011-04-01

    The movement toward Open Access continues to gain momentum. A brief review of APS efforts in this area will be presented by APS Editor in Chief, Gene Sprouse. Editors from Physical Review C, D, Letters, and X, Physical Review Special Topics - Accelerators and Beams, Physical Review Special Topics - Physics Education Research, and Reviews of Modern Physics will address your questions about publishing in this evolving environment.

  20. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (I): catastrophic APS, APS nephropathy and heart valve lesions.

    PubMed

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyse the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analysed on the catastrophic APS, APS nephropathy and heart valve lesions, and presents the recommendations elaborated by the Task Force after this analysis.

  1. APS Education and Diversity Efforts

    NASA Astrophysics Data System (ADS)

    Prestridge, Katherine; Hodapp, Theodore

    2015-11-01

    American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

  2. [Apheresis in antiphospholipid syndrome (APS)].

    PubMed

    De Silvestro, Giustina; Tison, Tiziana; Marson, Piero

    2012-01-01

    Antiphospholipid syndrome (APS) is a rare clinical disorder characterized by thromboembolic manifestations and/or obstetric complications. Along with the clinical symptoms and signs, serum antiphospholipid antibodies have to be detected. APS can be primary, i.e., without any concomitant disorders, or secondary to other autoimmune diseases, particularly systemic lupus erythematosus. Criteria for the diagnosis of APS have been clearly established. Hyperacute APS (or catastrophic antiphospholipid syndrome), often with a poor prognosis, must meet four criteria: involvement of three or more organs, rapid evolution of clinical manifestations, microangiopathic occlusion of small blood vessels at biopsy, and presence of antiphospholipid antibodies. The rationale for apheresis treatment is the removal of pathogenetic antibodies involved in the development of tissue damage. Our experience includes 23 patients, in particular 15 women treated for 19 pregnancies. According to the National Guidelines Program, the effectiveness of apheresis in catastrophic syndrome has a level of evidence of V/VI, with a strength of recommendation A; in highrisk pregnancy it has a level of evidence of V with a strength of recommendation B. It will be necessary to better define the prognosis of various categories of pregnant patients with APS, as well as useful laboratory parameters to monitor its clinical course and anticipate any complications of pregnancy.

  3. AP Human Geography and Success on the AP Test

    ERIC Educational Resources Information Center

    Roncone, John; Newhalfen, Nate

    2013-01-01

    Classroom projects that explore culture and globalization enhance the curriculum and help students see how geography directly connects to their lives. These authors contend that a project-based approach can supplement the teaching of an AP Human Geography course, and visualize this course as an essential tool for students to truly understand how…

  4. AP Geography, Environmental Science Thrive

    ERIC Educational Resources Information Center

    Robelen, Erik W.

    2012-01-01

    Geography may not be particularly known as a hot topic among today's students--even some advocates suggest it suffers from an image problem--but by at least one measure, the subject is starting to come into its own. Across more than 30 topics covered in the Advanced Placement (AP) program, participation in geography is rising faster than any…

  5. Coaching in the AP Classroom

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2013-01-01

    Many parallels exist between quality coaches and quality classroom teachers--especially AP teachers, who often feel the pressure to produce positive test results. Having developed a series of techniques and strategies for building a team-oriented winning culture on the field, Jim Fornaciari writes about how he adapted those methods to work in the…

  6. The APS in Public Affairs

    NASA Astrophysics Data System (ADS)

    Lustig, Harry

    2000-04-01

    Although the American Physical Society was created for the interchange of scientific ideas, the call to the founding meeting included the observation that the organization "could not fail to have an important influence in all matters affecting the interest of physicists". However for most of its history APS did not behave like "just another interest group in American society". Instead, at the beginning, it limited itself to such successful initiatives as the creation of the Bureau of Standards and such unsuccessful ones as adoption of the metric system. After World War II, speaking out on behalf of the freedom of science and scientists, such as Astin, Condon, and Oppenheimer, became important. In the 1970's, pushed by members, the Society became more "political", sponsoring sessions and studies on defense issues, taking a stand for the Equal Rights Amendment and creating the Panel on Public Affairs and the Forum on Physics and Society. Only in the last fifteen years has the APS unabashedly lobbied for the economic interests of physics and physicists. Adopting this new, if unavoidable role may have unintended consequences for the willingness and effectiveness of APS in speaking out on other public issues.

  7. An AP Calculus Classroom Amusement Park

    ERIC Educational Resources Information Center

    Ferguson, Sarah

    2016-01-01

    Throughout the school year, AP Calculus teachers strive to teach course content comprehensively and swiftly in an effort to finish all required material before the AP Calculus exam. As early May approaches and the AP Calculus test looms, students and teachers nervously complete lessons, assignments, and assessments to ensure student preparation.…

  8. Preparing Students for the AP Psychology Exam

    ERIC Educational Resources Information Center

    Whitlock, Kristin

    2013-01-01

    The Advanced Placement Psychology exam is one of the fastest growing exams offered by the College Board. The average percent of change in the number of students taking this exam over the past five years is 12.4%. With 238,962 students taking the exam in 2013, the AP Psychology exam is the sixth largest exam, surpassing AP Biology and AP World…

  9. AP reclamation and reuse in RSRM propellant

    NASA Technical Reports Server (NTRS)

    Miks, Kathryn F.; Harris, Stacey A.

    1995-01-01

    A solid propellant ingredient reclamation pilot plant has been evaluated at the Strategic Operations of Thiokol Corporation, located in Brigham City, Utah. The plant produces AP wet cake (95 percent AP, 5 percent water) for recycling at AP vendors. AP has been obtained from two standard propellant binder systems (PBAN and HTPB). Analytical work conducted at Thiokol indicates that the vendor-recrystallized AP meets Space Shuttle propellant specification requirements. Thiokol has processed 1-, 5-, and 600-gallon propellant mixes with the recrystallized AP. Processing, cast, cure, ballistic, mechanical, and safety properties have been evaluated. Phillips Laboratory static-test-fired 70-pound and 800-pound BATES motors. The data indicate that propellant processed with reclaimed AP has nominal properties.

  10. APS high heat load monochromator

    SciTech Connect

    Lee, W.K.; Mills, D.

    1993-02-01

    This document contains the design specifications of the APS high heat load (HHL) monochromator and associated accessories as of February 1993. It should be noted that work is continuing on many parts of the monochromator including the mechanical design, crystal cooling designs, etc. Where appropriate, we have tried to add supporting documentation, references to published papers, and calculations from which we based our decisions. The underlying philosophy behind performance specifications of this monochromator was to fabricate a device that would be useful to as many APS users as possible, that is, the design should be as generic as possible. In other words, we believe that this design will be capable of operating on both bending magnet and ID beamlines (with the appropriate changes to the cooling and crystals) with both flat and inclined crystal geometries and with a variety of coolants. It was strongly felt that this monochromator should have good energy scanning capabilities over the classical energy range of about 4 to 20 keywith Si (111) crystals. For this reason, a design incorporating one rotation stage to drive both the first and second crystals was considered most promising. Separate rotary stages for the first and second crystals can sometimes provide more flexibility in their capacities to carry heavy loads (for heavily cooled first crystals or sagittal benders of second crystals), but their tuning capabilities were considered inferior to the single axis approach.

  11. Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

    SciTech Connect

    FULLER, R.K.

    1999-02-23

    This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects. The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.

  12. Peculiar Traits of Coarse AP (Briefing Charts)

    DTIC Science & Technology

    2014-12-01

    at differing rates due to pressure and temperature influences in both isolated crystals and solid propellant combustions. Consolidated coarse AP...different reaction rates are also observed between low and high pressure confinements. In solid propellants coarse AP promotes dark zone combustion, low...release; distribution unlimited. PA clearance #. Porous AP in solid propellant Edwin L. Lista, China Lake Demonstrated 3.5 ips @ 2000 Burn rate pressure

  13. AP-2α and AP-2β regulate dorsal interneuron specification in the spinal cord.

    PubMed

    Xu, Xiaofeng; Liu, Zijing; Huang, Hao; Zheng, Kang; Hu, Xuemei; Zhang, Zunyi; Qiu, Mengsheng

    2017-01-06

    To date, five AP-2 genes that encode AP-2α, β, γ, δ and ε have been identified in vertebrates and they have been reported to be key regulators of embryonic development. However, the role of AP-2 family members in the development of central nervous system (CNS) has not been characterized. In the present study, we systematically examined the spatiotemporal expression pattern of AP-2 genes in the developing spinal cord of mouse and chick embryos and found that AP-2α and AP-2β are specifically expressed in post-mitotic dorsal interneurons. Loss-of-function analysis using in ovo electroporation in embryonic chick spinal cord preliminarily demonstrated that cAP-2α and cAP-2β regulates dorsal Class A and Class B interneuron specification, respectively. Gain-of-function experiments further revealed that misexpression of cAP-2α, but not cAP-2β, was able to induce the ectopic generation of Class A interneurons. Together, our studies indicated that AP-2 family members, AP-2α and AP-2β, have distinct functions in the regulation of dorsal interneuron development.

  14. APS undulator radiation: First results

    SciTech Connect

    Cai, Z.; Dejus, R.J.; Hartog, P.D.

    1995-12-31

    The first undulator radiation has been extracted from the Advanced Photon Source (APS). The results from the characterization of this radiation are very satisfactory. With the undulator set at a gap of 15.8 mm (K=1.61), harmonics as high as the 17th were observed using a crystal spectrometer. The angular distribution of the third-harmonic radiation was measured, and the source was imaged using a zone plate to determine the particle beam emittance. The horizontal beam emittance was found to be 6.9 {plus_minus} 1.0 nm-rad, and the vertical emittance coupling was found to be less than 3%. The absolute spectral flux was measured over a wide range of photon energies, and it agrees remarkably well with the theoretical calculations based on the measured undulator magnetic field profile and the measured beam emittance. These results indicate that both the emittance of the electron beam and the undulator magnetic field quality exceed the original specifications.

  15. AE8/AP8 Implementations in AE9/AP9, IRBEM, and SPENVIS

    DTIC Science & Technology

    2014-02-18

    radiation belt model, SHIELDOSE, AE8/AP8 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE...a wide range of locations within the radiation belts . The new AE9/AP9 model application includes the ability to query the legacy AE8 and AP8 models...trapped particle fluxes with the NASA models AP-8 and AE-8, Radiat . Meas., 26, pp. 947-952. International Association of Geomagnetism and Aeronomy

  16. AP Courses Get Audited for Quality

    ERIC Educational Resources Information Center

    Ashford, Ellie

    2007-01-01

    As the college admissions process has gotten much more competitive, the number of high school students taking Advanced Placement (AP) courses has soared. At the same time, policymakers and education leaders seek to get more minorities and students not on the college track to sign up for AP and other rigorous classes. But as high schools have…

  17. AP Music Theory in Your School.

    ERIC Educational Resources Information Center

    Lucia, Raymond

    1993-01-01

    Asserts that an Advanced Placement (AP) course in music theory offers student musicians opportunities to gain new insight into melody, harmony, and structure. Describes content and teaching methods used in an AP music theory program. Discusses necessary teacher characteristics and maintains that both students and teachers benefit from the course.…

  18. Resources for AP United States History.

    ERIC Educational Resources Information Center

    Ennis, Rosemary

    1999-01-01

    Discusses resources that can be used in an Advanced Placement (AP) U.S. history course, including a series of textbooks, supplemental readings, projects, Document-Based Questions and essays from earlier AP examinations, Internet and multimedia resources, and students and their families. (CMK)

  19. Advanced APS Impacts on Vehicle Payloads

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.; Reed, Brian D.

    1989-01-01

    Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethyl hydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination and scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

  20. Coaching Strategies for AP: Building a Successful AP European History Program

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2014-01-01

    The October 2013 special issue of "Social Education" dealt with almost all AP social studies subjects, but omitted AP European History. This is one of the most fascinating AP subjects for students and teachers alike. In this article, the author shares his experiences since hewas given the responsibility of building his school's Advanced…

  1. ELECTROCHEMICAL CORROSION TESTING OF TANKS 241-AN-102 & 241-AP-107 & 241-AP-108 IN SUPPORT OF ULTRASONIC TESTING

    SciTech Connect

    WYRWAS RB; DUNCAN JB

    2008-11-20

    This report presents the results of the corrosion rates that were measured using electrochemical methods for tanks 241-AN-102 (AN-102), 241-AP-107 (AP 107), and 241-AP-108 (AP-108) performed under test plant RPP-PLAN-38215. The steel used as materials of construction for AN and AP tank farms was A537 Class 1. Test coupons of A537 Class 1 carbon steel were used for corrosion testing in the AN-107, AP-107, and AP-108 tank waste. Supernate will be tested from AN-102, AP-107, and Ap-108. Saltcake testing was performed on AP-108 only.

  2. Development of the AP Technology Through Time

    NASA Astrophysics Data System (ADS)

    Charmier, F.; Martin, O.; Gariepy, R.

    2015-02-01

    This article presents the historical development of the AP Technology (Aluval, Voreppe, France) pot series starting with the AP13 in the 1960s, followed by the AP18 and the AP30 in the 1980s and 1990s. For most of the modern-era technology, from the late 1970s on, development has been based on a three-stage pattern, the first one being the pot modeling, followed by the pot prototype stage, and then the industrial stage, which fully validated the technology. This development pattern has proven to be successful since it has led to the very robust AP Technology pot design generation and a large number of greenfield smelters built in the 1990-2010 selected the AP Technology design. AP60 is the latest of this series: The development at the prototype level was initiated in the 1990s and is presented in the article. It is now followed by the first industrial realization at Jonquière with the startup in late 2013 and the full validation of the technology in mid-2014. The development of APXe, which aims at very low energy consumption, uses many common elements pertaining to the AP60 design and is presented in the article. AP Technology has also addressed the need for continuous and fast improvement of pot performances adapted to each existing client or site specifics; for this purpose, a new development methodology has recently emerged thanks to the very high modeling capabilities. This methodology, based on the validation of "technology bricks" and their integration in the final design following a strict process, is presented in the last section of this article.

  3. Tank 241-AP-107, grab samples, 7AP-99-1, 7AP-99-3 and 7AP-99-4 analytical results for the final report

    SciTech Connect

    BELL, K.E.

    1999-08-12

    This document is the format IV, final report for the tank 241-AP-107 (AP-107) grab samples taken in May 1999 to address waste compatibility concerns. Chemical, radiochemical, and physical analyses on the tank AP-107 samples were performed as directed in Compatibility Grab Sampling and Analysis Plan for Fiscal year 1999. Any deviations from the instructions provided in the tank sampling and analysis plan (TSAP) were discussed in this narrative. Interim data were provided earlier to River Protection Project (RPP) personnel, however, the data presented here represent the official results. No notification limits were exceeded.

  4. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  5. APS Activities with Other Professional Societies

    NASA Astrophysics Data System (ADS)

    Slakey, Francis

    2006-03-01

    In 1981, the APS Council issued a statement that opposed ``equal time'' presentation in public school science classes of creationism and evolution. The statement clarified that ``Scientific inquiry and religious beliefs are two distinct elements of the human experience. Attempts to present them in the same context can only lead to misunderstandings of both.'' The APS Council revisited the issue in 1999 when a school board in Kansas attempted to eliminate the Big Bang, among other issues, from the science curriculum. Since that time, the APS has been more directly involved in confronting efforts that would dilute the teaching of science in public school science classes. This talk will review the APS activities and describe a developing multi-science society activity.

  6. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) .

    PubMed

    Bauer, Peter; Leshinsky-Silver, Esther; Blumkin, Lubov; Schlipf, Nina; Schröder, Christopher; Schicks, Julia; Lev, Dorit; Riess, Olaf; Lerman-Sagie, Tally; Schöls, Ludger

    2012-02-01

    We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

  7. Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes.

    PubMed

    Theos, Alexander C; Tenza, Danièle; Martina, José A; Hurbain, Ilse; Peden, Andrew A; Sviderskaya, Elena V; Stewart, Abigail; Robinson, Margaret S; Bennett, Dorothy C; Cutler, Daniel F; Bonifacino, Juan S; Marks, Michael S; Raposo, Graça

    2005-11-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies.

  8. Automated Plasma Spray (APS) process feasibility study

    NASA Technical Reports Server (NTRS)

    Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

    1981-01-01

    An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal barrier coatings to aircraft and stationary gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical positioning subsystem incorporating two interlaced six degree of freedom assemblies (one for coating deposition and one for coating thickness monitoring); a noncoherent optical metrology subsystem (for in process gaging of the coating thickness buildup at specified points on the specimen); a microprocessor based adaptive system controller (to achieve the desired overall thickness profile on the specimen); and commerical plasma spray equipment. Over fifty JT9D first stage aircraft turbine blade specimens, ten W501B utility turbine blade specimens and dozens of cylindrical specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary turbine blade specimens achieved an overall coating thickness uniformity of 53 micrometers (2.1 mils), much better than is achievable manually. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were performed. One of the preliminary turbine blade evaluation specimens was subjected to a torch test and metallographic evaluation. Some cylindrical specimens coated with the APS process survived up to 2000 cycles in subsequent burner rig testing.

  9. Tank 241-AP-107, grab samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 analytical results for the final report

    SciTech Connect

    Steen, F.H.

    1997-12-22

    This document is the final report for tank 241-AP-107 grab samples. Three grab samples were collected from riser 1 on September 11, 1997. Analyses were performed on samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1997) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Rev. 1: Fowler, 1995; Rev. 2: Mulkey and Nuier, 1997). The analytical results are presented in the data summary report (Table 1). A notification was made to East Tank Farms Operations concerning low hydroxide in the tank and a hydroxide (caustic) demand analysis was requested. The request for sample analysis (RSA) (Attachment 2) received for AP-107 indicated that the samples were polychlorinated biphenyl (PCB) suspects. Therefore, prior to performing the requested analyses, aliquots were made to perform PCB analysis in accordance with the 222-S Laboratory administrative procedure, LAP-101-100. The results of this analysis indicated that no PCBs were present at 50 ppm and analysis proceeded as non-PCB samples. The results and raw data for the PCB analysis will be included in a revision to this document. The sample breakdown diagrams (Attachment 1) are provided as a cross-reference for relating the tank farm customer identification numbers with the 222-S Laboratory sample numbers and the portion of sample analyzed.

  10. Building an AP Social Studies Program with Non-Traditional AP Students

    ERIC Educational Resources Information Center

    Ashmead, Amanda; Blanchette, Sue

    2013-01-01

    Equal access to education, that is to a high quality education, has increasingly come to mean access to an Advanced Placement program. In recent years, there has been steady attention paid to opening access to AP programs. The 9th annual College Board report (2013) stated "students who succeed on an AP Exam during high school typically…

  11. The AP spectroscopic binary HD 59435 revisited

    NASA Astrophysics Data System (ADS)

    Wade, G. A.; Mathys, G.; North, P.

    1999-07-01

    HD 59435 is a double-lined spectroscopic binary, one component of which is a magnetic Ap star and the other a G8 or K0 giant (Wade et al. 1996). Both components are very slowly rotating, and the Ap star exhibits spectral lines resolved into their magneti cally-split components. Herein we report additional measurements of the mean magnetic field modulus of the Ap star, measurements of the radial velocities of both components, and Geneva photometry of the system, and discuss their impact upon conclusions drawn previously. Based on observations collected at the European Southern Observatory (La Silla, Chile; ESO Programme Nos. 56.E-0688, 58.E-0159, 60.E-0565). Table 3 is available only in electronic form at the CDS via anonymous ftp 130.79.128.5

  12. AP U.S. History: Beneficial or Problematic?

    ERIC Educational Resources Information Center

    Lurie, Maxine N.

    2000-01-01

    Warns against the declining standards of the Advanced Placement (AP) U.S. history examination and the AP program. Focuses on the problems that occur in maintaining high standards and the practive of teaching to the test in AP courses. Discusses who does grade and who should grade the AP examinations. (CMK)

  13. Commissioning Simulations for the APS Upgrade Lattice

    SciTech Connect

    Sajaev, V.; Borland, M.

    2015-01-01

    A hybrid seven-bend-achromat lattice that features very strong focusing elements and a relatively small vacuum chamber has been proposed for the APS upgrade. Achieving design lattice parameters during commissioning will need to be accomplished quickly in order to minimize dark time for APS users. The paper will describe start-to-end simulation of the machine commissioning beginning from first-turn trajectory correction, progressing to orbit and lattice correction, and culminating in evaluation of the nonlinear performance of the corrected lattice

  14. 77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year.... ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition. Catalog of Federal Domestic... 8848) a notice inviting applications for the AP Test Fee fiscal year (FY) 2012 competition (February...

  15. APS Ranks High on College Entrance Exams.

    ERIC Educational Resources Information Center

    APS in Action, 1984

    1984-01-01

    This document discusses the scores of Albuquerque (New Mexico) Public Schools (APS) students on the American College Test (ACT) and the Scholastic Aptitude Test (SAT) during the 1982-83 school year. Graphs, a map, and a question and answer format are used to report the information. Comparisons of average ACT scores and average SAT scores are drawn…

  16. APS deposition facility upgrades and future plans

    NASA Astrophysics Data System (ADS)

    Conley, Ray; Shi, Bing; Erdmann, Mark; Izzo, Scott; Assoufid, Lahsen; Goetze, Kurt; Mooney, Tim; Lauer, Kenneth

    2014-09-01

    The Advanced Photon Source (APS) has recently invested resources to upgrade or replace aging deposition systems with modern equipment. Of the three existing deposition systems, one will receive an upgrade, while two are being replaced. A design which adds a three-substrate planetary for the APS rotary deposition system is almost complete. The replacement for the APS large deposition system, dubbed the "Modular Deposition System", has been conceptually designed and is in the procurement process. Eight cathodes will sputter horizontally on mirrors up to 1.5 meters in length. This new instrument is designed to interface with ion-milling instruments and various metrology equipment for ion-beam figuring. A third linear machine, called the APS Profile Coating System, has two cathodes and is designed to accept substrates up to 200mm in length. While this machine is primarily intended for fabrication of figured KB mirrors using the profile-coating technique, it has also been used to produce multilayer monochromators for beamline use.

  17. The Demographic Wave: Rethinking Hispanic AP Trends

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Sawtell, Ellen

    2013-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Las Vegas, NV in July 2013. This presentation reviews new research examining the AP® experience of Hispanic graduates over the past decade. Topics include an in-depth look at the AP Spanish Language and Culture gateway hypothesis and trends in family characteristics such as parent…

  18. Boosting Black Academic Achievement and AP Enrollments

    ERIC Educational Resources Information Center

    Saunders, Terrie; Maloney, Kathy

    2005-01-01

    Minority students were about 25% of the student population at Central High School in Omaha, Nebraska, in 1995. But the composition of its honors and challenge classes did not reflect this diversity: Few minority students were taking challenge classes as underclassmen and even fewer were taking Advanced Placement (AP) courses as seniors. This paper…

  19. The Promise of AP World History

    ERIC Educational Resources Information Center

    Saldaña, Cristóbal T.

    2013-01-01

    AP World History is the ideal history course. It introduces students to 10,000 years of world history, and demands critical reading, critical writing, and critical thinking skills on the part of both the teacher and the students. It requires students to build their expertise in reading their textbook, and places demands on the teacher to assign…

  20. Gapminder: An AP Human Geography Lab Assignment

    ERIC Educational Resources Information Center

    Keller, Kenneth H.

    2012-01-01

    This lesson is designed as a lab assignment for Advanced Placement (AP) Human Geography students wherein they use the popular Gapminder web site to compare levels of development in countries from different world regions. For this lesson, it is important for the teacher to practice with Gapminder before giving the assignment to students. (Contains…

  1. College Board Readies Plans for AP Audits

    ERIC Educational Resources Information Center

    Klein, Alyson

    2006-01-01

    This article describes the educators mixed reviews regarding the audit system planned by the College Board to scrutinize high school Advanced Placement courses. Teachers of AP courses are required to submit materials to the College Board proving that their course syllabuses meet the program's curricular requirements. It is the most extensive…

  2. Structuring the AP Art History Course

    ERIC Educational Resources Information Center

    Herscher, Walter R.

    2013-01-01

    While AP (Advanced Placement) Art History may be taught within the art department in many schools, social studies teachers are equally capable of teaching the course well. They have the historical background to discuss the reasons for changes in art styles. A teacher's preparation is similar to teaching a course stressing political history,…

  3. Binaries among AP and AM stars

    NASA Astrophysics Data System (ADS)

    North, P.; Ginestet, N.; Carquillat, J.-M.; Carrier, F.; Udry, S.

    1998-04-01

    The results of long-term surveys of radial velocities of cool Ap and Am stars are presented. There are two samples, one of about 100 Ap stars and the other of 86 Am stars. Both have been observed with the CORAVEL scanner from Observatoire de Haute-Provence (CNRS), France. The conspicuous lack of short-period binaries among cool Ap stars seems confirmed, although this may be the result of an observational bias; one system has a period as short as 1.6 days. A dozen new orbits could be determined, including that of one SB2 system. Considering the mass functions of 68 binaries from the literature and from our work, we conclude that the distribution of the mass ratios is the same for the Bp-Ap stars than for normal G dwarfs. Among the Am stars, we found 52 binaries, i.e. 60%; an orbit could be computed for 29 of them. Among these 29, there are 7 SB2 systems, one triple and one quadruple system. The 21 stars with an apparently constant radial velocity may show up later as long-period binaries with a high eccentricity. The mass functions of the SB1 systems are compatible with cool main-sequence companions, also suggested by ongoing spectral observations.

  4. The AP Descriptive Chemistry Question: Student Errors

    ERIC Educational Resources Information Center

    Crippen, Kent; Brooks, David W.

    2005-01-01

    For over a decade, the authors have been involved in a design theory experiment providing software for high school students preparing for the descriptive question on the Advanced Placement (AP) chemistry examination. Since 1997, the software has been available as a Web site offering repeatable practice. This study describes a 4-year project during…

  5. Functional description of APS beamline front ends

    SciTech Connect

    Kuzay, T.

    1993-02-01

    Traditional synchrotron sources were designed to produce bending magnet radiation and have proven to be an essential scientific tool. Currently, a new generation of synchrotron sources is being built that will be able to accommodate a large number of insertion device (ID) and high quality bending magnet (BM) sources. One example is the 7-GeV Advanced Photon Source (APS) now under construction at Argonne National Laboratory. The research and development effort at the APS is designed to fully develop the potential of this new generation of synchrotron sources. Of the 40 straight sections in the APS storage ring, 34 will be available for IDs. The remaining six sections are reserved for the storage ring hardware and diagnostics. Although the ring incorporates 80 BMs, only 40 of them can be used to extract radiation. The accelerator hardware shadows five of these 40 bending magnets, so the maximum number of BM sources on the lattice is 35. Generally, a photon beamline consists of four functional sections. The first section is the ID or the BM, which provides the radiation source. The second section, which is immediately outside the storage ring but inside a concrete shielding tunnel, is the front end, which is designed to control, define, and/or confine the x-ray beam. In the case of the APS, the front ends are designed to confine the photon beam. The third section, just outside the concrete shielding tunnel and on the experimental floor, is the first optics enclosure, which contains optics to filter and monochromatize the photon beam. The fourth section of a beamline consists of beam transports, additional optics, and experiment stations to do the scientific investigations. This document describes only the front ends of the APS beamlines.

  6. Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001 in controlling tobacco diseases

    PubMed Central

    Maketon, Monchan; Apisitsantikul, Jirasak; Siriraweekul, Chatchai

    2008-01-01

    Two biological control agents, Bacillus subtilis AP-01 (Larminar™) and Trichoderma harzianum AP-001 (Trisan™) alone or/in combination were investigated in controlling three tobacco diseases, including bacterial wilt (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf spot (Cercospora nicotiana). Tests were performed in greenhouse by soil sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping off pathogens were drenched first and followed with the biological control agents and for comparison purposes, two chemical fungicides. But for frogeye leaf spot, which is an airborne fungus, a spraying procedure for every treatment including a chemical fungicide was applied instead of drenching. Results showed that neither B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt, but when combined, their controlling capabilities were as effective as a chemical treatment. These results were also similar for damping-off disease when used in combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001 resulted in a good frogeye leaf spot control, which was not significantly different from the chemical treatment. PMID:24031219

  7. Power Saving Control for Battery-Powered Portable WLAN APs

    NASA Astrophysics Data System (ADS)

    Ogawa, Masakatsu; Hiraguri, Takefumi

    This paper proposes a power saving control function for battery-powered portable wireless LAN (WLAN) access points (APs) to extend the battery life. The IEEE802.11 standard does not support power saving control for APs. To enable a sleep state for an AP, the AP forces the stations (STAs) to refrain from transmitting frames using the network allocation vector (NAV) while the AP is sleeping. Thus the sleep state for the AP can be employed without causing frame loss at the STAs. Numerical analysis and computer simulation reveal that the newly proposed control technique conserves power compared to the conventional control.

  8. APS control system operating system choice

    SciTech Connect

    Knott, M.; Kraimer, M.; Lenkszus, F.

    1990-05-01

    The purpose of this document is to set down the reasons and decisions regarding what is an important choice for the APS Control System design staff, namely the choice of an operating system for its principle computer resources. Since the choice also may affect cost estimates and the design handbook, there is a further need to document the process. The descriptions and explanations which follow are intended for reading by other APS technical area managers and will contain a minimum of buzz-words, and where buzz-words are used, they will be explained. The author hopes that it will help in understanding the current trends and developments in the volatile and fast-developing computer field.

  9. APS storage ring vacuum system performance

    SciTech Connect

    Noonan, J.R.; Gagliano, J.; Goeppner, G.A.

    1997-06-01

    The Advanced Photon Source (APS) storage ring was designed to operated with 7-GeV, 100-mA positron beam with lifetimes > 20 hours. The lifetime is limited by residual gas scattering and Touschek scattering at this time. Photon-stimulated desorption and microwave power in the rf cavities are the main gas loads. Comparison of actual system gas loads and design calculations will be given. In addition, several special features of the storage ring vacuum system will be presented.

  10. Final report for tank 241-AP-108, grab samples 8AP-96-1, 8AP-96-2 and 8AP-96-FB

    SciTech Connect

    Esch, R.A.

    1996-04-19

    This document is the final report deliverable for the tank 241-AP-108 grab samples. The samples were subsampled and analyzed in accordance with the TSAP. Included in this report are the results for the Waste Compatibility analyses, with the exception of DSC and thermogravimetric analysis (TGA) results which were presented in the 45 Day report (Part 2 of this document). The raw data for all analyses, with the exception of DSC and TGA, are also included in this report.

  11. Cultural Diversity in AP Art History

    ERIC Educational Resources Information Center

    Bolte, Frances R.

    2006-01-01

    Teaching AP Art History is like running on a treadmill that is moving faster than a teacher can run. Many teachers are out of breath before the end of the term and wonder how in the world they can cover every chapter. Because time is short and art from pre-history through to the present, including the non-European traditions, must be covered, this…

  12. An Updated AP2 Beamline TURTLE Model

    SciTech Connect

    Gormley, M.; O'Day, S.

    1991-08-23

    This note describes a TURTLE model of the AP2 beamline. This model was created by D. Johnson and improved by J. Hangst. The authors of this note have made additional improvements which reflect recent element and magnet setting changes. The magnet characteristics measurements and survey data compiled to update the model will be presented. A printout of the actual TURTLE deck may be found in appendix A.

  13. A WWW Database of APS POSS Images

    NASA Astrophysics Data System (ADS)

    Cornuelle, C. S.; Aldering, G.; Sourov, A.; Humphreys, R. M.; Larsen, J.; Cabanela, J.

    1996-05-01

    We are making our digitized images from the APS scans of the red and blue first-epoch Palomar Observatory Sky Survey (POSS I) available as a WWW-accessible image database. Image requests are through the APS homepage at http://isis.spa.umn.edu, and are initially limited in field width and sky region. To create this database, images from each scanned POSS I plate are processed into a set of coordinate-referenced index and pixel files. Database management software then refers to each object's pixels within a requested sky region by plate, by sub-plate, and finally by each scanned image. These images are then assembled into a mosaic FITS format file, whose header contains astrometric and photometric information. While the current APS Catalog of the POSS I contains only matched images, the image database will include all images above the plate grain noise limit of 25 mu m in diameter. Thus for a given sky region, users will have access to both the object (star and galaxy) catalog data and to the actual pixel data. This project is sponsored by NASA ADP contract NAS5-32670.

  14. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

    PubMed

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

  15. Small Molecule Inhibitors Targeting Activator Protein 1 (AP-1)

    PubMed Central

    2015-01-01

    Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases. PMID:24831826

  16. Small molecule inhibitors targeting activator protein 1 (AP-1).

    PubMed

    Ye, Na; Ding, Ye; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2014-08-28

    Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases.

  17. Book Eyes Impact of AP Classes and Exams

    ERIC Educational Resources Information Center

    Viadero, Debra

    2010-01-01

    At a time of mushrooming interest in Advanced Placement (AP) tests, a new book, "AP: A Critical Examination of the Advanced Placement Program," assembles studies on how capable the program is of meeting the increasingly diverse expectations held up for it. Growing out of a symposium held at Harvard in 2007, the book focuses on AP science…

  18. The AP Exam and the Introductory College Course.

    ERIC Educational Resources Information Center

    Pushkin, David B.

    1995-01-01

    Explores reasons why students take introductory physics courses at the university regardless of their Advanced Placement (AP) exam performance. Briefly describes the nature of AP physics, the examination format and reporting of scores, and the results of a survey of physics departments regarding their policies towards AP exam scores and placement…

  19. 75 FR 75666 - Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... Advanced Placement (AP) Test Fee Program AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year (FY) 2011 competition. SUMMARY... applications for the AP Test Fee FY 2011 competition. That notice established a November 17, 2010 deadline...

  20. AP600 containment purge radiological analysis

    SciTech Connect

    O`Connor, M.; Schulz, J.; Tan, C.

    1995-02-01

    The AP600 Project is a passive pressurized water reactor power plant which is part of the Design Certification and First-of-a-Kind Engineering effort under the Advanced Light Water Reactor program. Included in this process is the design of the containment air filtration system which will be the subject of this paper. We will compare the practice used by previous plants with the AP600 approach to meet the goals of industry standards in sizing the containment air filtration system. The radiological aspects of design are of primary significance and will be the focus of this paper. The AP600 Project optimized the design to combine the functions of the high volumetric flow rate, low volumetric flow rate, and containment cleanup and other filtration systems into one multi-functional system. This achieves a more simplified, standardized, and lower cost design. Studies were performed to determine the possible concentrations of radioactive material in the containment atmosphere and the effectiveness of the purge system to keep concentrations within 10CFR20 limits and within offsite dose objectives. The concentrations were determined for various reactor coolant system leakage rates and containment purge modes of operation. The resultant concentrations were used to determine the containment accessibility during various stages of normal plant operation including refueling. The results of the parametric studies indicate that a dual train purge system with a capacity of 4,000 cfm per train is more than adequate to control the airborne radioactivity levels inside containment during normal plant operation and refueling, and satisfies the goals of ANSI/ANS-56.6-1986 and limits the amount of radioactive material released to the environment per ANSI/ANS 59.2-1985 to provide a safe environment for plant personnel and offsite residents.

  1. Ozone mitigation tests at the APS

    SciTech Connect

    Kuzay, T.M.; Collins, J.T.; Pisharody, M.; Job, P.K.; Wang Zhibi

    1996-09-01

    Ozone is generated in the APS experimental stations whenever the x-ray beam has a chance to interact with air. Ozone concentrations in an experimental station have to be below a certain defined limit (current OSHA regulations specify 0.08 ppm as the maximum limit) before an experimenter can reenter the hutch. This limit is said to be currently under study for a downward adjustment. One method of depleting the ozone generated in an experimental station is mitigation through either adsorption or direct destruction. In recent tests, both methods were tried using commercially available units. Test results and some analytical predictions are presented.

  2. The APS machine protection system (MPS)

    SciTech Connect

    Fuja, R.; Berg, B.; Arnold, N.

    1996-08-01

    The machine protection system (MPS) that protects the APS storage ring vacuum chamber from x-ray beams, is active. There are over 650 sensors monitored and networked through the MPS system. About the same number of other process variables are monitored by the much slower EPICS control system, which also has an input to the rf abort chain. The MPS network is still growing with the beam position limits detection system coming on-line. The network configuration, along with a limited description of individual subsystems, is presented.

  3. Cold-fusion television show angers APS

    NASA Astrophysics Data System (ADS)

    Cartwright, Jon

    2009-06-01

    Cold fusion has been controversial since its inception on 23 March 1989, when chemists Martin Fleischmann and Stanley Pons at the University of Utah in the US announced that they had achieved a sustained nuclear-fusion reaction at room temperature. Two decades on, a US television documentary about the field has stirred up fresh debate after it linked the American Physical Society (APS) to an evaluation of some cold-fusion results by Robert Duncan, a physicist and vice chancellor of the University of Missouri.

  4. Antioxidants and AP-1 activation: a brief overview.

    PubMed

    Gomez del Arco, P; Martínez-Martínez, S; Calvo, V; Armesilla, A L; Redondo, J M

    1997-12-01

    Activity of the transcription factor AP-1 is controlled by different MAPK cascades that regulate the different AP-1 components at the transcriptional and posttranscriptional level. Recently, AP-1 has been shown to behave as a redox-sensitive transcription factor that can be induced under both pro-oxidative and antioxidative conditions. In this overview we summarize the signaling pathways that converge on the activation of AP-1 and the components of these pathways that have been shown to be targets of antioxidants. The activation of AP-1 by antioxidants may account for the expression of a number of genes that mediate important functions under physiological conditions.

  5. The Electronic ApJ in Context

    NASA Astrophysics Data System (ADS)

    Biemesderfer, C. D.

    1995-12-01

    The on-line edition of the Astrophysical Journal provides the first opportunity for astronomical researchers to interact with the literature in a network context. Other electronic journals will follow. Astronomers will continue to develop ways to take advantage of information on the network, and these will be most effective when ApJ articles, observations from data centers, proposals for telescope time, communications with collaborators, and so on, are meshed. Astronomical literature, as a resource on the Internet, is not unique from the viewpoint of function or management, and astronomers are not unique as scholars in their desire to use the Internet as a tool to advance their work. We need to ensure as a community that all our resources for research --- journals and data --- fit in a global context on an Internet being used by everyone. In other words, we have to be sure that the ApJ fits into all the digital libraries of the future, including the ones we don't build. This paper will present a scenario in which many varied forms of information, astronomical and otherwise, can be catalogued and distributed so that they can be discovered and used by the research community.

  6. Component Database for the APS Upgrade

    SciTech Connect

    Veseli, S.; Arnold, N. D.; Jarosz, D. P.; Carwardine, J.; Decker, G.; Schwarz, N.

    2016-01-01

    The Advanced Photon Source Upgrade (APS-U) project will replace the existing APS storage ring with a multi-bend achromat (MBA) lattice to provide extreme transverse coherence and extreme brightness x-rays to its users. As the time to replace the existing storage ring accelerator is of critical concern, an aggressive one-year removal/installation/testing period is being planned. To aid in the management of the thousands of components to be installed in such a short time, the Component Database (CDB) application is being developed with the purpose to identify, document, track, locate, and organize components in a central database. Three major domains are being addressed: Component definitions (which together make up an exhaustive "Component Catalog"), Designs (groupings of components to create subsystems), and Component Instances (“Inventory”). Relationships between the major domains offer additional "system knowledge" to be captured that will be leveraged with future tools and applications. It is imperative to provide sub-system engineers with a functional application early in the machine design cycle. Topics discussed in this paper include the initial design and deployment of CDB, as well as future development plans.

  7. Correction magnet power supplies for APS machine

    SciTech Connect

    Kang, Y.G.

    1991-04-01

    A number of correction magnets are required for the advanced photon source (APS) machine to correct the beam. There are five kinds of correction magnets for the storage ring, two for the injector synchrotron, and two for the positron accumulator ring (PAR). Table I shoes a summary of the correction magnet power supplies for the APS machine. For the storage ring, the displacement of the quadrupole magnets due to the low frequency vibration below 25 Hz has the most significant effect on the stability of the positron closed orbit. The primary external source of the low frequency vibration is the ground motion of approximately 20 {mu}m amplitude, with frequency components concentrated below 10 Hz. These low frequency vibrations can be corrected by using the correction magnets, whose field strengths are controlled individually through the feedback loop comprising the beam position monitoring system. The correction field require could be either positive or negative. Thus for all the correction magnets, bipolar power supplies (BPSs) are required to produce both polarities of correction fields. Three different types of BPS are used for all the correction magnets. Type I BPSs cover all the correction magnets for the storage ring, except for the trim dipoles. The maximum output current of the Type I BPS is 140 Adc. A Type II BPS powers a trim dipole, and its maximum output current is 60 Adc. The injector synchrotron and PAR correction magnets are powered form Type III BPSs, whose maximum output current is 25 Adc.

  8. RELAP5/MOD3 AP600 problems

    SciTech Connect

    Riemke, R.A.

    1993-08-01

    RELAP5/MOD3 is a reactor systems analysis code that has been developed jointly by the US Nuclear Regulatory Commission (USNRC) and a consortium consisting of several of the countries and domestic organizations that were members of the International Code Assessment and Applications Program (ICAP). The code is currently being used to simulate transients for the next generation of advanced light water reactors (ALWR`s). One particular reactor design is the Westinghouse AP600 pressurized water reactor (PWR), which consists of two hot legs and four cold legs as well as passive emergency core cooling (ECC) systems. Initial calculations with RELAP5/MOD3 indicated that the code was not as robust as RELAP5/MOD2.5 with regard to AP600 calculations. Recent modifications in the areas of condensation wall heat transfer, interfacial heat transfer in the presence of noncondensibles, bubbly flow interfacial heat transfer, and time smoothing of both interfacial drag and interfacial heat transfer have improved the robustness, although more reliability is needed.

  9. EPA’s AP-42 development methodology: Converting or rerating current AP-42 datasets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” instructs that the ratings of the...

  10. Trichomonas vaginalis: the adhesins AP51 and AP65 bind heme and hemoglobin.

    PubMed

    Ardalan, Shahed; Lee, B Craig; Garber, Gary E

    2009-04-01

    Trichomonas vaginalis is the cause of human trichomoniasis, the most common non-viral sexually transmitted disease worldwide. Although acquisition of iron by binding to host hemoglobin through distinct receptor(s) has been described, no specific heme- or hemoglobin-binding site has been reported in this parasite. To determine the presence of hemoglobin-binding protein(s), membrane proteins were subjected to hemoglobin-affinity chromatography. Eluted proteins were analysed by SDS-PAGE. Two protein bands of 48 and 63 kDa were detected. Competition assay with an excess amount of hemoglobin or hemin in hemoglobin-affinity chromatography could block the 63- and 48-kDa bands, respectively. Further analysis by mass spectrometry indicated that the 48- and 63-kDa proteins had identity with two T. vaginalis adhesins: AP51 and AP65, respectively. This study confirms the existence of multifunctional proteins in T. vaginalis, and suggested that AP51 and AP65, besides serving as adhesion molecules, could also act as heme- and hemoglobin-binding proteins.

  11. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

    PubMed

    Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

  12. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

  13. The Cryptosporidium parvum ApiAP2 gene family: insights into the evolution of apicomplexan AP2 regulatory systems

    PubMed Central

    Oberstaller, Jenna; Pumpalova, Yoanna; Schieler, Ariel; Llinás, Manuel; Kissinger, Jessica C.

    2014-01-01

    We provide the first comprehensive analysis of any transcription factor family in Cryptosporidium, a basal-branching apicomplexan that is the second leading cause of infant diarrhea globally. AP2 domain-containing proteins have evolved to be the major regulatory family in the phylum to the exclusion of canonical regulators. We show that apicomplexan and perkinsid AP2 domains cluster distinctly from other chromalveolate AP2s. Protein-binding specificity assays of C. parvum AP2 domains combined with motif conservation upstream of co-regulated gene clusters allowed the construction of putative AP2 regulons across the in vitro life cycle. Orthologous Apicomplexan AP2 (ApiAP2) expression has been rearranged relative to the malaria parasite P. falciparum, suggesting ApiAP2 network rewiring during evolution. C. hominis orthologs of putative C. parvum ApiAP2 proteins and target genes show greater than average variation. C. parvum AP2 domains display reduced binding diversity relative to P. falciparum, with multiple domains binding the 5′-TGCAT-3′, 5′-CACACA-3′ and G-box motifs (5′-G[T/C]GGGG-3′). Many overrepresented motifs in C. parvum upstream regions are not AP2 binding motifs. We propose that C. parvum is less reliant on ApiAP2 regulators in part because it utilizes E2F/DP1 transcription factors. C. parvum may provide clues to the ancestral state of apicomplexan transcriptional regulation, pre-AP2 domination. PMID:24957599

  14. ATP6AP1 — EDRN Public Portal

    Cancer.gov

    ATP6AP1 is an integral membrane protein composed of at least 10 subunits. It is responsible for acidifying various eukaryotic intracellular organelles. ATP6AP1, also known as vacuolar ATPase or V-ATPase, has a cytosolic V1 domain and a transmembrane V0 domain. The acidification performed by ATP6AP1 is necessary for intracellular processes such as protein sorting, zymogen activation, and receptor-mediated endocytosis.

  15. 76 FR 10269 - AP1000 Design Certification Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... aircraft, incorporate design improvements, and increase standardization of the design. Upon NRC rulemaking... standardization and improved licensing efficiency for the multiple COL applications referencing the AP1000...

  16. Project W-211, initial tank retrieval systems, description of operations for 241-AP-102 and 241-AP-104

    SciTech Connect

    RIECK, C.A.

    1999-02-25

    The primary purpose of the Initial Tank Retrieval Systems (ITRS) is to provide systems for retrieval of radioactive wastes stored in underground double-shell tanks (DSTS) for transfer to alternate storage, evaporation, pretreatment or treatment, while concurrently reducing risks associated with safety watch list and other DSTs. This Description of Operations (DOO) defines the control philosophy for the waste retrieval system for tanks 241-AP-102 (AP-102) and 241-AP-104 (AP-104). This DOO will provide a basis for the detailed design of the Retrieval Control System (RCS) for AP-102 and AP-104 and establishes test criteria for the RCS. The test criteria will be used during qualification testing and acceptance testing to verify operability.

  17. Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor

    PubMed Central

    Kaneko, Izumi; Iwanaga, Shiroh; Kato, Tomomi; Kobayashi, Issei; Yuda, Masao

    2015-01-01

    Stage-specific transcription is a fundamental biological process in the life cycle of the Plasmodium parasite. Proteins containing the AP2 DNA-binding domain are responsible for stage-specific transcriptional regulation and belong to the only known family of transcription factors in Plasmodium parasites. Comprehensive identification of their target genes will advance our understanding of the molecular basis of stage-specific transcriptional regulation and stage-specific parasite development. AP2-O is an AP2 family transcription factor that is expressed in the mosquito midgut-invading stage, called the ookinete, and is essential for normal morphogenesis of this stage. In this study, we identified the genome-wide target genes of AP2-O by chromatin immunoprecipitation-sequencing and elucidate how this AP2 family transcription factor contributes to the formation of this motile stage. The analysis revealed that AP2-O binds specifically to the upstream genomic regions of more than 500 genes, suggesting that approximately 10% of the parasite genome is directly regulated by AP2-O. These genes are involved in distinct biological processes such as morphogenesis, locomotion, midgut penetration, protection against mosquito immunity and preparation for subsequent oocyst development. This direct and global regulation by AP2-O provides a model for gene regulation in Plasmodium parasites and may explain how these parasites manage to control their complex life cycle using a small number of sequence-specific AP2 transcription factors. PMID:26018192

  18. Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

    PubMed Central

    Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

    2005-01-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

  19. A single Beta adaptin contributes to AP1 and AP2 complexes and clathrin function in Dictyostelium

    PubMed Central

    Sosa, R. Thomas; Weber, Michelle M.; Wen, Yujia; O’Halloran, Theresa J.

    2011-01-01

    The assembly of clathrin-coated vesicles is important for numerous cellular processes, including nutrient uptake and membrane organization. Important contributors to clathrin assembly are four tetrameric Assembly Proteins, also called Adaptor Proteins (AP’s), each of which contains a beta subunit. We identified a single beta subunit, named β1/2, that contributes to both the AP1 and AP2 complexes of Dictyostelium. Disruption of the gene encoding β1/2 resulted in severe defects in growth, cytokinesis, and development. Additionally, cells lacking β1/2 displayed profound osmoregulatory defects including the absence of contractile vacuoles and mislocalization of contractile vacuole markers. The phenotypes of β1/2 were most similar to previously described phenotypes of clathrin and AP1 mutants, supporting a particularly important contribution of AP1 to clathrin pathways in Dictyostelium cells. The absence of β1/2 in cells led to significant reductions in the protein amounts of the medium-sized subunits of the AP1 and AP2 complexes, establishing a role for the beta subunit in the stability of the medium subunits. Dictyostelium β1/2 could resemble a common ancestor of the more specialized β1 and β2 subunits of the vertebrate AP complexes. Our results support the essential contribution a single beta subunit to the stability and function AP1 and AP2 in a simple eukaryote. PMID:22050483

  20. The AP2-like gene NsAP2 from water lily is involved in floral organogenesis and plant height.

    PubMed

    Luo, Huolin; Chen, Sumei; Jiang, Jiafu; Teng, Nianjun; Chen, Yu; Chen, Fadi

    2012-07-01

    APETALA2 (AP2) genes are ancient and widely distributed among the seed plants, and play an important role during the plant life cycle, acting as key regulators of many developmental processes. In this study, an AP2 homologue, NsAP2, was characterized from water lily (Nymphaea sp. cv. 'Yellow Prince') and is believed to be rather primitive in the evolution of the angiosperms. In situ RNA hybridization showed that NsAP2 transcript was present in all regions of the floral primordium, but had the highest level in the emerging floral organ primordium. After the differentiation of floral organs, NsAP2 was strongly expressed in sepals and petals, while low levels were found in stamens and carpels. The NsAP2 protein was suggested to be localized in the cell nucleus by onion transient expression experiment. Overexpression of NsAP2 in Arabidopsis led to more petal numbers, and Arabidopsis plants expressing NsAP2 exhibited higher plant height, which may be a result of down-regulated expression of GA2ox2 and GA2ox7. Our results indicated that the NsAP2 protein may function in flower organogenesis in water lily, and it is a promising gene for plant height improvement.

  1. BioCAT undulator beamline at APS

    NASA Astrophysics Data System (ADS)

    Bunker, G. B.; Irving, T.; Black, E.; Zhang, K.; Fischetti, R.; Wang, S.; Stepanov, S.

    1997-07-01

    The Biophysics Collaborative Access Team (BioCAT) project will be an outstanding research facility for biological small angle scattering, non-crystalline diffraction, and x-ray absorption spectroscopy at the Advanced Photon Source, Argonne National Labs. BioCAT operates as an NIH Research Resource under a cooperative agreement with NIH. BioCat has an aggressive program of core and collaborative research, service, and training. Central to the facility is the undulator beam line (designed by G. Rosenbaum, Argonne National Labs) capable of delivering ca. 1013-1014 ph/s to the sample. Focusing optics will allow focal spot ranges from 1.5×3.5 mm to 30×80 micron, independently adjustable in the vertical and horizontal direction. Up to 8 m camera lengths can be accommodated in the 12m experimental enclosure. The accessible beam energy range will be from 3.5-13 keV using the undulator fundamental and 10-40 keV using the third harmonic. Energy resolution will exceed 2×10-4 ΔE/E. Detectors will include image plates, CCD detectors and some novel detectors designed to accommodate the high count rates expected at the APS. The multi-element detector will be a very high count-rate (up to 109 ph/s global), one dimensional detector optimized for scattering applications. We are also developing a multilayer analyzer detector which maximizes solid angle of collection with high background rejection for biological spectroscopy applications.

  2. Eastman, AP start on coal unit

    SciTech Connect

    1995-10-25

    Eastman Chemical and Air Products and Chemicals (AP) have started construction of a $214-million, coal-to-methanol demonstration unit at Eastmans site in Kingsport, TN. The project is part of the Department of Energy`s clean coal technology program and is receiving $93 million in federal support. The demonstration unit-which will have a methanol capacity of 260 tons/day-will use novel catalyst technology for converting coal-derived synthesis gas (syngas) to methanol. Unlike conventional technology that processes syngas through a fixed bed of dry catalyst particles, the liquid-phase methanol process converts the syngas in a single vessel containing catalysts suspended in mineral oil. The companies say the innovation allows the process to better able handle the gases from coal gasifiers and is more stable and reliable than existing processes. Eastman says it will use the methanol produced by the plant as a chemical feedstock. It currently uses methanol as an intermediate in making acetic anhydride and dimethyl terephthalate. In addition, the companies say the methanol will be evaluated as a feedstock in making methyl tert-butyl ether for reformulated fuels. Eastman also says it will evaluate coproducing dimethyl ether (DME) with the methanol. DME can be used as a fuel additive or blended with methanol for a chemical feedstock, according to Eastman.

  3. High Pressure Reverse Flow APS Engine

    NASA Technical Reports Server (NTRS)

    Senneff, J. M.

    1972-01-01

    A design and test demonstration effort was undertaken to evaluate the concept of the reverse flow engine for the APS engine application. The 1500 lb (6672 N) thrust engine was designed to operate on gaseous hydrogen and gaseous oxygen propellants at a mixture ratio of 4 and to achieve the objective performance of 435 sec (4266 Nsec/kg) specific impulse. Superimposed durability requirements called for a million-cycle capability with 50 hours duration. The program was undertaken as a series of tasks including the initial preliminary design, design of critical test components and finally, the design and demonstration of an altitude engine which could be used interchangeably to examine operating parameters as well as to demonstrate the capability of the concept. The program results are reported with data to indicate that all of the program objectives were met or exceeded within the course of testing on the program. The analysis effort undertaken is also reported in detail and supplemented with test data in some cases where prior definitions could not be made. The results are contained of these analyses as well as the test results conducted throughout the course of the program. Finally, the test data and analytical results were combined to allow recommendations for a flight weight design. This preliminary design effort is also detailed.

  4. The APS SASE FEL : modeling and code comparison.

    SciTech Connect

    Biedron, S. G.

    1999-04-20

    A self-amplified spontaneous emission (SASE) free-electron laser (FEL) is under construction at the Advanced Photon Source (APS). Five FEL simulation codes were used in the design phase: GENESIS, GINGER, MEDUSA, RON, and TDA3D. Initial comparisons between each of these independent formulations show good agreement for the parameters of the APS SASE FEL.

  5. Data-Based Decision Making: The Road to AP Equity

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Duggan, Odette

    2012-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Lake Buena Vista, FL in July 2012. This presentation reviews concepts central to achieving equitable AP access and success for all willing and academically prepared students. We analyze trends in participation and performance by race/ethnicity from the AP Report to the Nation and…

  6. AP-102/104 Retrieval control system qualification test procedure

    SciTech Connect

    RIECK, C.A.

    1999-05-18

    This Qualification Test Procedure documents the results of the qualification testing that was performed on the Project W-211, ''Initial Tank Retrieval Systems,'' retrieval control system (RCS) for tanks 241-AP-102 and 241-AP-104. The results confirm that the RCS has been programmed correctly and that the two related hardware enclosures have been assembled in accordance with the design documents.

  7. Performance of Project Advance Students on the AP Biology Examination.

    ERIC Educational Resources Information Center

    Mercurio, Joseph; And Others

    1984-01-01

    Compared performance of Project Advance biology students (N=60) with Advanced Placement (AP) candidates (N=15,947) nationally on College Entrance Examination Board AP biology test. The research, conducted to determine comparability of the program as valid measures of academic achievement, determined that Project Advance students scored above the…

  8. Raising Rigor, Getting Results: Lessons Learned from AP Expansion

    ERIC Educational Resources Information Center

    Wakelyn, David

    2009-01-01

    Advanced Placement (AP), which enables high school students to take introductory college-level courses, is the nation's oldest example of a rigorous, common curriculum. Students who score well on AP exams are more likely to persist in college and earn a degree. The Advanced Placement Expansion project of the National Governors Association Center…

  9. AP233: An Information Model for Systems Engineering

    NASA Technical Reports Server (NTRS)

    Siebes, Georg

    2009-01-01

    In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

  10. AccuNet/AP (Associated Press) Multimedia Archive

    ERIC Educational Resources Information Center

    Young, Terrence E., Jr.

    2004-01-01

    The AccuNet/AP Multimedia Archive is an electronic library containing the AP's current photos and a selection of pictures from their enormous print and negative library, as well as text and graphic material. It is composed of two photo databases as well as graphics, text, and audio databases. The features of this database are briefly described in…

  11. AP: A Critical Examination of the Advanced Placement Program

    ERIC Educational Resources Information Center

    Sadler, Philip M.; Sonnert, Gerhard; Tai, Robert; Klopfenstein, Kirstin

    2016-01-01

    The Advanced Placement (AP) program was created to enhance the experience of gifted students as they transition from high school to college. "AP: A Critical Examination of the Advanced Placement Program," edited by Philip M. Sadler, Gerhard Sonnert, Robert Tai, and Kirstin Klopfenstein (2010, Harvard Education Press), questions the…

  12. A Closer Examination of the Academic Benefits of AP

    ERIC Educational Resources Information Center

    McKillip, Mary E. M.; Rawls, Anita

    2013-01-01

    The authors sought to better understand the relationship between students participating in the Advanced Placement (AP) program and subsequent performance on the Scholastic Aptitude Test (SAT). Focusing on students graduating from U.S. public high schools in 2010, the authors used propensity scores to match junior year AP examinees in 3 subjects to…

  13. Content Validation Studies of the AP Chemistry Examination.

    ERIC Educational Resources Information Center

    Taft, Hessy L.

    1990-01-01

    Described is a curriculum survey of general chemistry courses at the college level and an evaluation survey of the advanced placement chemistry examination. Results indicated that the AP chemistry course should remain broad in coverage and should expand its laboratory component. Analyses also indicated that the AP exam was appropriate and valid.…

  14. GPI-AP release in cellular, developmental, and reproductive biology.

    PubMed

    Fujihara, Yoshitaka; Ikawa, Masahito

    2016-04-01

    Glycosylphosphatidylinositol-anchored proteins (GPI-APs) contain a covalently linked GPI anchor located on outer cell membranes. GPI-APs are ubiquitously conserved from protozoa to vertebrates and are critical for physiological events such as development, immunity, and neurogenesis in vertebrates. Both membrane-anchored and soluble GPI-APs play a role in regulating their protein conformation and functional properties. Several pathways mediate the release of GPI-APs from the plasma membrane by vesiculation or cleavage. Phospholipases and putative substrate-specific GPI-AP-releasing enzymes, such as NOTUM, glycerophosphodiesterase 2, and angiotensin-converting enzyme, have been characterized in mammals. Here, the protein modifications resulting from the cleavage of the GPI anchor are discussed in the context of its physiological functions.

  15. AP-2α inhibits hepatocellular carcinoma cell growth and migration.

    PubMed

    Huang, Wenhuan; Chen, Cheng; Liang, Zhongheng; Qiu, Junlu; Li, Xinxin; Hu, Xiang; Xiang, Shuanglin; Ding, Xiaofeng; Zhang, Jian

    2016-03-01

    Transcription factor AP-2α is involved in many types of human cancers, but its role in hepatocellular carcinogenesis is largely unknown. In this study, we found that expression of AP-2α was low in 40% of human hepatocellular cancers compared with adjacent normal tissues by immunohistochemical analysis. Moreover, AP-2α expression was low or absent in hepatocellular cancer cell lines (HepG2, Hep3B, SMMC-7721 and MHHC 97-H). Human liver cancer cell lines SMMC-7721 and Hep3B stably overexpressing AP-2α were established by lentiviral infection and puromycin screening, and the ectopic expression of AP-2α was able to inhibit hepatocellular cancer cell growth and proliferation by cell viability, MTT assay and liquid colony formation in vitro and in vivo. Furthermore, AP-2α overexpression decreased liver cancer cell migration and invasion as assessed by wound healing and Transwell assays, increasing the sensitivity of liver cancer cells to cisplatin analyzed by MTT assays. Also AP-2α overexpression suppressed the sphere formation and renewed the ability of cancer stem cells. Finally, we found that AP-2α is epigenetically modified and modulates the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), β-catenin, p53, EMT, and CD133 expression in liver cancer cell lines. These results suggested that AP-2α expression is low in human hepatocellular cancers by regulating multiple signaling to affect hepatocellular cancer cell growth and migration. Therefore, AP-2α might represent a novel potential target in human hepatocellular cancer therapy.

  16. Stratification in Ap star atmospheres: Simulations

    NASA Astrophysics Data System (ADS)

    Cowley, Charles R.; Castelli, Fiorella

    2017-01-01

    It is now well established that the atmospheres of Ap stars can be chemically stratified (cf. Babel, A\\&A 258, 645, 1992; Ryabchikova et al. A\\&A 384, 545, 2002). The most convincing cases have been made with the profiles of very strong lines, such as Ca II K. Weaker line profiles are less obvious indicators. The collective behavior of sets or groups of lines have also been used. For example, if higher abundances are derived for strong lines in an atmosphere with zero microturbulence, one may assume that the absorbing species has been pushed into the higher photospheres. An example are the medium-strong Mn II lines in HgMn stars. In this paper, we probe this assumption by calculating line strengths with various assumed stratification models, and then determining abundances from those lines using an {\\bf unstratified} model with the same Teff and log(g). We use the model from Castelli, Kurucz \\& and Hubrig (A\\&A, 508, 401, 2009) for HR 6000, whose spectrum shows numerous indications of stratification. A variety of stratification models are considered, for example, ones where the majority of an absorbing species is concentrated above (or below) $log(\\tau_{5000}$ = -2.0. Cloud models are also investigated, where a species is concentrated within a range of photospheric depths. Curves of growth are generated in unstratified atmospheres for lines by holding the abundance fixed, and increasing log(gf). Similar curves are made in stratified models, and the ratios of strong to weak linesare compared with and without stratification. The effects of stratification on ionization are also investigated, as well as on the profiles of strong lines. We find, in agreement with previous work, that severe abundance jumps are sometimes required to account for some of the observed peculiarities.

  17. Thermal Decomposition Characteristics of Orthorhombic Ammonium Perchlorate (o-AP) and an 0-AP/HTPB-Based Propellant

    SciTech Connect

    BEHRENS JR.,RICHARD; MINIER,LEANNA M.G.

    1999-10-25

    A study to characterize the low-temperature reactive processes for o-AP and an AP/HTPB-based propellant (class 1.3) is being conducted in the laboratory using the techniques of simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) and scanning electron microscopy (SEM). The results presented in this paper are a follow up of the previous work that showed the overall decomposition to be complex and controlled by both physical and chemical processes. The decomposition is characterized by the occurrence of one major event that consumes up to {approx}35% of the AP, depending upon particle size, and leaves behind a porous agglomerate of AP. The major gaseous products released during this event include H{sub 2}O, O{sub 2}, Cl{sub 2}, N{sub 2}O and HCl. The recent efforts provide further insight into the decomposition processes for o-AP. The temporal behaviors of the gas formation rates (GFRs) for the products indicate that the major decomposition event consists of three chemical channels. The first and third channels are affected by the pressure in the reaction cell and occur at the surface or in the gas phase above the surface of the AP particles. The second channel is not affected by pressure and accounts for the solid-phase reactions characteristic of o-AP. The third channel involves the interactions of the decomposition products with the surface of the AP. SEM images of partially decomposed o-AP provide insight to how the morphology changes as the decomposition progresses. A conceptual model has been developed, based upon the STMBMS and SEM results, that provides a basic description of the processes. The thermal decomposition characteristics of the propellant are evaluated from the identities of the products and the temporal behaviors of their GFRs. First, the volatile components in the propellant evolve from the propellant as it is heated. Second, the hot AP (and HClO{sub 4}) at the AP-binder interface oxidize the binder through reactions that

  18. apGA: An adaptive parallel genetic algorithm

    SciTech Connect

    Liepins, G.E. ); Baluja, S. )

    1991-01-01

    We develop apGA, a parallel variant of the standard generational GA, that combines aggressive search with perpetual novelty, yet is able to preserve enough genetic structure to optimally solve variably scaled, non-uniform block deceptive and hierarchical deceptive problems. apGA combines elitism, adaptive mutation, adaptive exponential scaling, and temporal memory. We present empirical results for six classes of problems, including the DeJong test suite. Although we have not investigated hybrids, we note that apGA could be incorporated into other recent GA variants such as GENITOR, CHC, and the recombination stage of mGA. 12 refs., 2 figs., 2 tabs.

  19. AP600 design certification thermal hydraulics testing and analysis

    SciTech Connect

    Hochreiter, L.E.; Piplica, E.J.

    1995-09-01

    Westinghouse Electric Corporation, in conjunction with the Department of Energy and the Electric Power Research Institute, have been developing an advanced light water reactor design; the AP600. The AP600 is a 1940 Mwt, 600Mwe unit which is similar to a Westinghouse two-loop Pressurized Water Reactor. The accumulated knowledge on reactor design to reduce the capital costs, construction time, and the operational and maintenance cost of the unit once it begins to generate electrical power. The AP600 design goal is to maintain an overall cost advantage over fossil generated electrical power.

  20. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner

    PubMed Central

    Alford, Justine E.; Marongiu, Michela; Watkins, Gemma L.

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release. PMID:27392064

  1. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner.

    PubMed

    Alford, Justine E; Marongiu, Michela; Watkins, Gemma L; Anderson, Emma C

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release.

  2. Modulation of AP-1 activity by nitric oxide (NO) in vitro: NO-mediated modulation of AP-1.

    PubMed

    Tabuchi, A; Sano, K; Oh, E; Tsuchiya, T; Tsuda, M

    1994-08-29

    To understand the role of nitric oxide (NO) in controlling the specific DNA-binding activities of transcriptional factors, we investigated the in vitro effect of the NO-donor sodium nitroprusside (SNP) on the AP-1 activity of cultured mouse cerebellar granule cells. A gel-mobility assay showed that SNP inhibited AP-1 activity in the presence, but not the absence of dithiothreitol (DTT). This DTT-dependent inhibition of AP-1 activity by SNP corresponded with the activation of the chemical reactivity of SNP with DTT, which can be monitored by the production of nitrite (NO2-). In contrast, diamide, a typical sulfhydryl oxidizing agent, inhibited AP-1 activity in the absence of DTT and its inhibitory effect was reversed competitively by DTT. Studies using structurally or functionally related analogues of SNP demonstrated that S-nitrosylation of the AP-1 moiety mediated by some NO-carriers but not by free NO, which can be produced by the chemical reaction of SNP with DTT, was responsible for the inhibition of AP-1 activity, suggesting NO-mediated regulation of the AP-1 transcriptional factor.

  3. QCD on the Massively Parallel Computer AP1000

    NASA Astrophysics Data System (ADS)

    Akemi, K.; Fujisaki, M.; Okuda, M.; Tago, Y.; Hashimoto, T.; Hioki, S.; Miyamura, O.; Takaishi, T.; Nakamura, A.; de Forcrand, Ph.; Hege, C.; Stamatescu, I. O.

    We present the QCD-TARO program of calculations which uses the parallel computer AP1000 of Fujitsu. We discuss the results on scaling, correlation times and hadronic spectrum, some aspects of the implementation and the future prospects.

  4. A hot-spare injector for the APS linac.

    SciTech Connect

    Lewellen, J. W.

    1999-04-13

    Last year a second-generation SSRL-type thermionic cathode rf gun was installed in the Advanced Photon Source (APS) linac. This gun (referred to as ''gun2'') has been successfully commissioned and now serves as the main injector for the APS linac, essentially replacing the Koontz-type DC gun. To help ensure injector availability, particularly with the advent of top-up mode operation at the APS, a second thermionic-cathode rf gun will be installed in the APS linac to act as a hot-spare beam source. The hot-spare installation includes several unique design features, including a deep-orbit Panofsky-style alpha magnet. Details of the hot-spare beamline design and projected performance are presented, along with some plans for future performance upgrades.

  5. DETAIL VIEW OF AP 50, MAIN FLOOR LEVEL, PLATFORM BSOUTH, ...

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

    DETAIL VIEW OF AP 50, MAIN FLOOR LEVEL, PLATFORM B-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  6. DETAIL VIEW OF AP 65, SECOND FLOOR LEVEL, PLATFORM DSOUTH, ...

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

    DETAIL VIEW OF AP 65, SECOND FLOOR LEVEL, PLATFORM D-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  7. DETAIL VIEW OF AP 66, MAIN FLOOR LEVEL, PLATFORM BNORTH, ...

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

    DETAIL VIEW OF AP 66, MAIN FLOOR LEVEL, PLATFORM B-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  8. Engaging Cuban Physicists Through the APS/CPS Partnership

    NASA Astrophysics Data System (ADS)

    Lerch, Irving A.; Lerch, Irving A.

    In his reflections on Cuban physics, Marcelo Alonso urges APS to take steps to promote interactions between Cuban and US physicists. As an introduction to Marcello's essay, this note will summarize past and current activities.

  9. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes

    PubMed Central

    Sitaram, Anand; Dennis, Megan K.; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Bonifacino, Juan S.; Marks, Michael S.

    2012-01-01

    Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. PMID:22718909

  10. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes.

    PubMed

    Sitaram, Anand; Dennis, Megan K; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S; Sviderskaya, Elena V; Bennett, Dorothy C; Raposo, Graça; Bonifacino, Juan S; Marks, Michael S

    2012-08-01

    Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine-based sorting signal in the pigment cell-specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1- and AP-3-favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs.

  11. Thermal Decomposition Characteristics of Orthorhombic Ammonium Perchlorate (o-AP)

    SciTech Connect

    Behrens, R.; Minier, L.

    1999-03-01

    Preliminary STMBMS and SEM results of the thermal decomposition of AP in the orthorhombic phase are presented. The overall decomposition is shown to be complex and controlled by both physical and chemical processes. The data show that the physical and chemical processes can be probed and characterized utilizing SEM and STMBMS. The overall decomposition is characterized by three distinguishing features: an induction period, and accelerator period and a deceleratory period. The major decomposition event occurs in the subsurface of the AP particles and propagates towards the center of the particle with time. The amount of total decomposition is dependent upon particle size and increases from 23% for {approximately}50{micro}m-diameter AP to 33% for {approximately}200{micro}m-diameter AP. A conceptual model of the physical processes is presented. Insight into the chemical processes is provided by the gas formation rates that are measured for the gaseous products. To our knowledge, this is the first presentation of data showing that the chemical and physical decomposition processes can be identified from one another, probed and characterized at the level that is required to better understand the thermal decomposition behavior of AP. Future work is planned with the goal of obtaining data that can be used to develop a mathematical description for the thermal decomposition of o-AP.

  12. Ontogenesis of Ap-2γ expression in rat testes.

    PubMed

    Hou, M; Stukenborg, J-B; Nurmio, M; Andersson, M; Toppari, J; Söder, O; Jahnukainen, K

    2011-01-01

    Searching for useful markers of spermatogonial stem cells and their differentiation, we used rat testes from ages representing different stages of testicular maturation to investigate the expression profile of transcription factor activation protein-2γ (Ap-2γ). The immunohistochemical and immunocytochemical evaluation using Ap-2γ and promyelocytic leukemia zinc finger in combination with sorting of CD9 and CD90 positive cells (undifferentiated spermatogonia) by fluorescence-activated cell sorting was performed. Our experiments revealed that Ap-2γ is detectable in testes of late fetal age and up to 60 days postnatally and is expressed in gonocytes and spermatogonia from late fetal age throughout all maturational stages. Restricted nuclear expression of Ap-2γ to undifferentiated male germ cells was verified by coexpression of Ap-2γ with promyelocytic leukemia zinc finger in sections of paraffin-embedded testes as well as in cells sorted positive for CD9 and CD90 expression. Our study demonstrated clearly that nuclear expression of Ap-2γ is a useful marker for identifying undifferentiated male germ cells, although its functional role is yet to be fully explored.

  13. DNA cleavage at the AP site via β-elimination mediated by the AP site-binding ligands.

    PubMed

    Abe, Yukiko S; Sasaki, Shigeki

    2016-02-15

    DNA is continuously damaged by endogenous and exogenous factors such as oxidation and alkylation. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form the abasic sites (AP sites). The alkylating antitumor agent exhibits cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. In this study, we have examined the effects of the nucleobase-polyamine conjugated ligands (G-, A-, C- and T-ligands) on the cleavage of the AP site. The G- and A-ligands cleaved DNA at the AP site by promoting β-elimination in a non-selective manner by the G-ligand, and in a selective manner for the opposing dT by the A-ligand. These results suggest that the nucleobase-polyamine conjugate ligands may have the potential for enhancement of the cytotoxicities of the AP site.

  14. AP@home: The Artificial Pancreas Is Now at Home.

    PubMed

    Heinemann, Lutz; Benesch, Carsten; DeVries, J Hans

    2016-07-01

    In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union-funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 "final studies" during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a "single-port AP system" was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners.

  15. Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

    PubMed Central

    Bhardwaj, Rita; Skelly, Patrick J.

    2011-01-01

    Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the blood; by impeding host immunological signaling pathways we suggest that tegumental molecules help create an immunologically privileged environment for schistosomes. In this work, we clone and characterize a schistosome alkaline phosphatase (SmAP), a predicted ∼60 kDa glycoprotein that has high sequence conservation with members of the alkaline phosphatase protein family. The SmAP gene is most highly expressed in intravascular parasite life stages. Using immunofluorescence and immuno-electron microscopy, we confirm that SmAP is expressed at the host/parasite interface and in internal tissues. The ability of living parasites to cleave exogenous adenosine monophosphate (AMP) and generate adenosine is very largely abolished when SmAP gene expression is suppressed following RNAi treatment targeting the gene. These results lend support to the hypothesis that schistosome surface enzymes such as SmAP could dampen host immune responses against the parasites by generating immunosuppressants such as adenosine to promote their survival. This notion does not rule out other potential functions for the adenosine generated e.g. in parasite nutrition. PMID:21483710

  16. The role of AP-1 and epigenetics in ALCL.

    PubMed

    Schiefer, Ana-Iris; Vesely, Paul; Hassler, Melanie R; Egger, Gerda; Kenner, Lukas

    2015-06-01

    Anaplastic large cell lymphoma (ALCL) is an aggressive, highly proliferative, T-cell lymphoma with increasing incidence worldwide. Anaplastic Lymphoma Kinase (ALK) fusions occur in about 50% of all cases. Most ALK positive cases of ALCL harbor the t(2;5) translocation that leads to expression of Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK). NPM-ALK induces a variety of oncogenic signaling pathways that lead to malignant transformation of T-cells via Activator Protein-1 (AP-1), STAT3 and other (transcription) factors. In addition to the commonly known AP-1 activators Mitogen-Activated Protein Kinases (MAPKs), there are other signaling pathways, such as PI3K/mTOR/AKT, which are implicated in AP-1 activation/expression in ALCL. The AP-1 factor JUNB was shown to drive ALCL proliferation and the expression of the characteristic ALCL Ki-1 antigen, CD30. cJUN and JUNB target PDGFRB, thereby leading to tumor progression and dissemination. Furthermore, aberrant gene expression in ALCL is frequently accompanied by changes in epigenetic regulatory mechanisms, such as DNA methylation patterns. Here, we discuss the role of AP-1 in the pathogenesis of ALCL and provide an overview of pathological epigenetic changes in ALCL cells.

  17. CD2AP Regulates SUMOylation of CIN85 in Podocytes

    PubMed Central

    Niedenthal, Rainer; Klaus, Malte; Teng, Beina; Worthmann, Kirstin; King, Benjamin L.; Peterson, Kevin J.; Haller, Hermann

    2012-01-01

    Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown that full-length CIN85 is upregulated in podocytes in the absence of CD2AP, whereas in wild-type cells, full-length CIN85 is not detectable. In this study, we show that full-length CIN85 is postranslationally modified by SUMOylation in wild-type podocytes. We can demonstrate that CIN85 is SUMOylated by SUMO-1, -2, and -3 and that SUMOylation is enhanced in the presence of CD2AP. Conversion of lysine 598 to arginine completely abolishes SUMOylation and leads to increased binding of CIN85 to nephrin. Our results indicate a novel role for CD2AP in regulating posttranslational modification of CIN85. PMID:22203040

  18. Prevention of aspiration pneumonia (AP) with oral care.

    PubMed

    Tada, Akio; Miura, Hiroko

    2012-01-01

    AP is a major cause of morbidity and mortality in elderly patients, especially frail elderly patients. The aim of this article is to review effect of oral care, including oral hygiene and improvement of oral function, on the prevention of AP among elderly people in hospitals and nursing homes. There is now a substantial body of work studying the effect of oral care on the prevention of respiratory diseases. Oral hygiene, consisting of oral decontamination and mechanical cleaning by dental professionals, has resulted in significant clinical effects (decreased incidence of pneumonia and decreased mortality from respiratory diseases) in clinical randomized trials. Moreover, studies examining oral colonization by pneumonia pathogens have shown the effect of oral hygiene on eliminating these pathogens. In addition, swallowing training has been shown to improve the movement and function of swallowing-related muscles, also resulting in decreased incidence of pneumonia. These findings support the contention that oral care is effective in the prevention of AP.

  19. Interaction of PARP-2 with AP site containing DNA.

    PubMed

    Kutuzov, Mikhail M; Khodyreva, Svetlana N; Ilina, Ekaterina S; Sukhanova, Maria V; Amé, Jean-Christophe; Lavrik, Olga I

    2015-05-01

    In eukaryotes the stability of genome is provided by functioning of DNA repair systems. One of the main DNA repair pathways in eukaryotes is the base excision repair (BER). This system requires precise regulation for correct functioning. Two members of the PARP family - PARP-1 and PARP-2, which can be activated by DNA damage - are widely considered as regulators of DNA repair processes, including BER. In contrast to PARP-1, the role of PARP-2 in BER has not been extensively studied yet. Since AP site is one of the most frequent type of DNA damage and a key intermediate of BER at the stage preceding formation of DNA breaks, in this paper we focused on the characterization of PARP-2 interaction with AP site-containing DNAs. We demonstrated that PARP-2, like PARP-1, can interact with the intact AP site via Schiff base formation, in spite of crucial difference in the structure of the DNA binding domains of these PARPs. By cross-linking of PARPs to AP DNA, we determined that the N-terminal domains of both PARPs are involved in formation of cross-links with AP DNA. We have also confirmed that DNA binding by PARP-2, in contrast to PARP-1, is not modulated by autoPARylation. PARP-2, like PARP-1, can inhibit the activity of APE1 by binding to AP site, but, in contrast to PARP-1, this inhibitory influence is hardly regulated by PAR synthesis. At the same time, 5'-dRP lyase activity of both PARPs is comparable, although being much weaker than that of Pol β, which is considered as the main 5'-dRP lyase of the BER process.

  20. Psychosocial Assessment of Artificial Pancreas (AP): Commentary and Review of Existing Measures and Their Applicability in AP Research

    PubMed Central

    Hood, Korey K.; Weissberg-Benchell, Jill; Aldred, Chris; Oliver, Nick; Laffel, Lori

    2015-01-01

    Abstract Aim: This study aimed to systematically review the evidence base for the use of existing psychological and psychosocial measures suitable for use in artificial pancreas (AP) research. Materials and Methods: This systematic review of published literature, gray literature, previous systematic reviews, and qualitative and economic studies was conducted using terms and abbreviations synonymous with diabetes, AP, and quality of life (QoL). Results: Two hundred ninety-two abstracts were identified that reported psychosocial assessment of diabetes-related technologies. Of these, nine met the inclusion criteria and were included. Only four of 103 ongoing trials evaluated psychosocial aspects as an outcome in the trial. Of these, treatment satisfaction, acceptance and use intention of AP, fear of hypoglycemia episodes, satisfaction with AP, and an unspecified QoL measure were used. Conclusions: A better understanding of the psychosocial side of AP systems and the extent to which human factors play a role in the uptake and efficient use of these systems will ultimately lead to the most benefit for people with diabetes. PMID:25549042

  1. AP Report to the Nation: A Closer Look at the Nation and Florida

    ERIC Educational Resources Information Center

    Sawtell, Ellen A.; Gillie, Jacqueline M.; Smith, Patricia Z.

    2012-01-01

    In February 2012, the College Board published The 8th Annual AP Report to the Nation. This session provides a deeper dive into key information for the United States with an emphasis on Florida, and participants hear how one school in Florida utilizes AP Potential™ to help build their AP Program. Participants also learn about AP participation and…

  2. Past, Present, and Future of AP Chemistry: A Brief History of Course and Exam Alignment Efforts

    ERIC Educational Resources Information Center

    Magrogan, Serena

    2014-01-01

    As part of the Advanced Placement (AP) Program's commitment to continually enhance alignment with current best practices in college-level learning, the AP Program is currently evaluating and redesigning courses and exams, one of which launched during the 2013-2014 academic school year: AP chemistry. The history of the AP chemistry course and…

  3. Radiation measurements during cavities conditioning on APS RF test stand

    SciTech Connect

    Grudzien, D.M.; Kustom, R.L.; Moe, H.J.; Song, J.J.

    1993-07-01

    In order to determine the shielding structure around the Advanced Photon Source (APS) synchrotron and storage ring RF stations, the X-ray radiation has been measured in the near field and far field regions of the RF cavities during the normal conditioning process. Two cavity types, a prototype 352-MHz single-cell cavity and a 352-MHz five-cell cavity, are used on the APS and are conditioned in the RF test stand. Vacuum measurements are also taken on a prototype 352-MHz single-cell cavity and a 352-MHz five-cell cavity. The data will be compared with data on the five-cell cavities from CERN.

  4. On the abundance of Europium. [in Ap and Am stars

    NASA Technical Reports Server (NTRS)

    Hartoog, M. R.; Cowley, C. R.; Adelman, S. J.

    1974-01-01

    The inclusion of the effects of hyperfine splitting can significantly lower the abundance estimate of Eu from singly ionized lines which lie on the flat portion of the curve of growth. In the 21 cool Ap stars studied by Adelman and the five Am stars studied by Smith, the Eu abundance was reduced by 0.4 dex on the average. In individual cases, the reductions were as great as 0.9 dex. This makes the Eu abundance comparable to that of its neighboring rare earths Sm and Gd in the Ap stars and less than Sm and Gd in the Am stars, but still substantially overabundant with respect to solar values.

  5. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features.

    PubMed

    Tüysüz, Beyhan; Bilguvar, Kaya; Koçer, Naci; Yalçınkaya, Cengiz; Çağlayan, Okay; Gül, Ece; Sahin, Sezgin; Çomu, Sinan; Günel, Murat

    2014-07-01

    Adaptor protein complex-4 (AP4) is a component of intracellular transportation of proteins, which is thought to have a unique role in neurons. Recently, mutations affecting all four subunits of AP4 (AP4M1, AP4E1, AP4S1, and AP4B1) have been found to cause similar autosomal recessive phenotype consisting of tetraplegic cerebral palsy and intellectual disability. The aim of this study was analyzing AP4 genes in three new families with this phenotype, and discussing their clinical findings with an emphasis on neuroimaging and facial features. Using homozygosity mapping followed by whole-exome sequencing, we identified two novel homozygous mutations in AP4M1 and a homozygous deletion in AP4B1 in three pairs of siblings. Spastic tetraplegia, microcephaly, severe intellectual disability, limited speech, and stereotypic laughter were common findings in our patients. All patients also had similar facial features consisting of coarse and hypotonic face, bitemporal narrowing, bulbous nose with broad nasal ridge, and short philtrum which were not described in patients with AP4M1 and AP4B1 mutations previously. The patients presented here and previously with AP4M1, AP4B1, and AP4E1 mutations shared brain abnormalities including asymmetrical ventriculomegaly, thin splenium of the corpus callosum, and reduced white matter volume. The patients also had hippocampal globoid formation and thin hippocampus. In conclusion, disorders due to mutations in AP4 complex have similar neurological, facial, and cranial imaging findings. Thus, these four genes encoding AP4 subunits should be screened in patients with autosomal recessive spastic tetraplegic cerebral palsy, severe intellectual disability, and stereotypic laughter, especially with the described facial and cranial MRI features.

  6. The AP-1 transcription factor homolog Pf-AP-1 activates transcription of multiple biomineral proteins and potentially participates in Pinctada fucata biomineralization.

    PubMed

    Zheng, Xiangnan; Cheng, Minzhang; Xiang, Liang; Liang, Jian; Xie, Liping; Zhang, Rongqing

    2015-09-25

    Activator protein-1 (AP-1) is an important bZIP transcription factor that regulates a series of physiological processes by specifically activating transcription of several genes, and one of its well-chartered functions in mammals is participating in bone mineralization. We isolated and cloned the complete cDNA of a Jun/AP-1 homolog from Pinctada fucata and called it Pf-AP-1. Pf-AP-1 had a highly conserved bZIP region and phosphorylation sites compared with those from mammals. A tissue distribution analysis showed that Pf-AP-1 was ubiquitously expressed in P. fucata and the mRNA level of Pf-AP-1 is extremely high in mantle. Pf-AP-1 expression was positively associated with multiple biomineral proteins in the mantle. The luciferase reporter assay in a mammalian cell line showed that Pf-AP-1 significantly up-regulates the transcriptional activity of the promoters of KRMP, Pearlin, and Prisilkin39. Inhibiting the activity of Pf-AP-1 depressed the expression of multiple matrix proteins. Pf-AP-1 showed a unique expression pattern during shell regeneration and pearl sac development, which was similar to the pattern observed for biomineral proteins. These results suggest that the Pf-AP-1 AP-1 homolog is an important transcription factor that regulates transcription of several biomineral proteins simultaneously and plays a role in P. fucata biomineralization, particularly during pearl and shell formation.

  7. Nuclear Reactor Safety--The APS Submits its Report

    ERIC Educational Resources Information Center

    Physics Today, 1975

    1975-01-01

    Presents the summary section of the American Physical Society (APS) report on the safety features of the light-water reactor, reviews the design, construction, and operation of a reactor and outlines the primary engineered safety features. Summarizes the major recommendations of the study group. (GS)

  8. Modeling Contaminants in AP-MS/MS Experiments

    PubMed Central

    Lavallée-Adam, Mathieu; Cloutier, Philippe; Coulombe, Benoit; Blanchette, Mathieu

    2015-01-01

    Identification of protein–protein interactions (PPI) by affinity purification (AP) coupled with tandem mass spectrometry (AP-MS/MS) produces large data sets with high rates of false positives. This is in part because of contamination at the AP level (due to gel contamination, nonspecific binding to the TAP columns in the context of tandem affinity purification, insufficient purification, etc.). In this paper, we introduce a Bayesian approach to identify false-positive PPIs involving contaminants in AP-MS/MS experiments. Specifically, we propose a confidence assessment algorithm (called Decontaminator) that builds a model of contaminants using a small number of representative control experiments. It then uses this model to determine whether the Mascot score of a putative prey is significantly larger than what was observed in control experiments and assigns it a p-value and a false discovery rate. We show that our method identifies contaminants better than previously used approaches and results in a set of PPIs with a larger overlap with databases of known PPIs. Our approach will thus allow improved accuracy in PPI identification while reducing the number of control experiments required. PMID:21117706

  9. Tead and AP1 Coordinate Transcription and Motility.

    PubMed

    Liu, Xiangfan; Li, Huapeng; Rajurkar, Mihir; Li, Qi; Cotton, Jennifer L; Ou, Jianhong; Zhu, Lihua J; Goel, Hira L; Mercurio, Arthur M; Park, Joo-Seop; Davis, Roger J; Mao, Junhao

    2016-02-09

    The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1-3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells.

  10. An On-Line Database of APS POSS Images

    NASA Astrophysics Data System (ADS)

    Cornuelle, C. S.; Aldering, G.; Sourov, A.; Thurmes, P.; Humphreys, R. M.

    We are making available our digitized images from the APS scans of the red and blue first-epoch Palomar Observatory Sky Survey (POSS I) photographic plates, forming an on-line image database. Image requests are through the APS homepage at URL http://isis.spa.umn.edu/homepage.aps.html and are initially limited in field width and sky region. To create this database, images from each scanned POSS I plate are processed into a set of coordinate-referenced index and pixel files. Database management software then refers to each object's pixels within a requested sky region by plate, by sub-plate, and finally by each scanned image. These images are then assembled into a mosaic FITS format file, whose header contains astrometric and photometric information. While the current APS Catalog of the POSS I includes only matched images, the image database will include images above 25 mu m in diameter. Thus for a given sky region, users have access to both the object (star and galaxy) catalog data and to the actual pixel data. This project is sponsored by NASA ADP contract NAS5-32670.

  11. APS Chapter 1 Evaluation Report 1984-1985.

    ERIC Educational Resources Information Center

    Kaemper, Jack; Morse, Kathy

    This report describes and evaluates the Albuquerque Public Schools (APS) 1984-85 Chapter 1 instructional program and its effect on student performance. The following information is reported or described: (1) conclusions and recommendations; (2) participating schools and cost summaries; (3) identification of eligible schools; (4) identification of…

  12. Effective Teaching Strategies for Open Enrollment Honors and AP Classes

    ERIC Educational Resources Information Center

    Winebrenner, Susan

    2006-01-01

    A trend is emerging to open enrollment for honors and AP classes to all students who wish to take them. Teachers of these open enrollment classes may be facing several dilemmas. How can the high standards and academic rigor of the course be maintained? How can students who struggle to learn be supported in their endeavors to keep up with the…

  13. Time Trials--An AP Physics Challenge Lab

    ERIC Educational Resources Information Center

    Jones, David

    2009-01-01

    I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…

  14. AP: A Critical Examination of the Advanced Placement Program

    ERIC Educational Resources Information Center

    Sadler, Philip M., Ed.; Sonnert, Gerhard, Ed.; Tai, Robert H., Ed.; Klopfenstein, Kristin, Ed.

    2010-01-01

    With an annual yearly growth rate of 9.3 percent over the last two decades, Advanced Placement courses have become a juggernaut in American high school education. AP courses are routinely perceived as an indicator of educational rigor, and many schools push to enroll low-income or minority students in these courses in the hope of preparing them…

  15. Approximate entropy (ApEn) as a complexity measure

    NASA Astrophysics Data System (ADS)

    Pincus, Steve

    1995-03-01

    Approximate entropy (ApEn) is a recently developed statistic quantifying regularity and complexity, which appears to have potential application to a wide variety of relatively short (greater than 100 points) and noisy time-series data. The development of ApEn was motivated by data length constraints commonly encountered, e.g., in heart rate, EEG, and endocrine hormone secretion data sets. We describe ApEn implementation and interpretation, indicating its utility to distinguish correlated stochastic processes, and composite deterministic/ stochastic models. We discuss the key technical idea that motivates ApEn, that one need not fully reconstruct an attractor to discriminate in a statistically valid manner—marginal probability distributions often suffice for this purpose. Finally, we discuss why algorithms to compute, e.g., correlation dimension and the Kolmogorov-Sinai (KS) entropy, often work well for true dynamical systems, yet sometimes operationally confound for general models, with the aid of visual representations of reconstructed dynamics for two contrasting processes.

  16. The AP Lever for Boosting Access, Success, and Equity

    ERIC Educational Resources Information Center

    Roegman, Rachel; Hatch, Thomas

    2016-01-01

    Four New Jersey school districts worked together to increase student achievement by applying a number of strategies focused on getting traditionally underrepresented students to take more AP courses. The districts are members of the New Jersey Network of Superintendents (NJNS), comprising 15 superintendents who work together to develop systemwide…

  17. DETAIL VIEW OF WINCH USED TO RAISE AND LOWER AP ...

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

    DETAIL VIEW OF WINCH USED TO RAISE AND LOWER AP 93W, ROOF LEVEL, PLATFORM D-SOUTH, HB-3, FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  18. Integrating Particulate Representations into AP Chemistry and Introductory Chemistry Courses

    ERIC Educational Resources Information Center

    Prilliman, Stephen G.

    2014-01-01

    The College Board's recently revised curriculum for advanced placement (AP) chemistry places a strong emphasis on conceptual understanding, including representations of particle phenomena. This change in emphasis is informed by years of research showing that students could perform algorithmic calculations but not explain those calculations…

  19. A process definition repository based on step AP 213

    SciTech Connect

    Butler, J.W.

    1997-09-01

    Over the years, in the context of numerically controlled machined part manufacturing, the loss, misinterpretation, and redundancy of re-inputting manufacturing instructions and data during the evolution of a product design into the finished product has been a resource depleting and costly endeavor. It is the intent of this project to utilize the emerging standards from the International Standards Organization, ISO 10303 Standard for the Exchange of Product Model Data, commonly referred to as STEP, to store and retrieve process planning information for a set of production work instructions. The project focuses on the utilization of the 1995 version of the Draft International Standard ISO/DIS 10303-213:1995 (E) Application protocol: Numerical control process plans for machined parts (AP213). This project illustrates the methodologies used to build an object-oriented Process Definition Repository (PDR), describes both the benefits and shortcomings experienced in implementing AP213, and recommends enhancements to AP213 for process planning information. The deliverable will be a Part 21 data file, based on the application-interpreted model for AP213 and integrated with product design data.

  20. Automated Procurement System (APS) revised project management plan (DS-03)

    NASA Technical Reports Server (NTRS)

    Murphy, Diane R.

    1995-01-01

    The Project Plan is the governing document for the implementation of the Automated Procurement System (APS). It includes a description of the proposed system, describes the work to be done, establishes a schedule of deliverables, and discusses the major standards and procedures to be followed.

  1. ACTIVATION OF AP-1 IN UROTSA CELLS BY METHYLATED ARSENICALS

    EPA Science Inventory

    ACTIVATION OF AP-1 IN UROTSA CELLS BY METHYLATED TRIVALENT ARSENICALS. Z Drobna1, I Jaspers2, D J Thomas3 and M Styblo1. 1Department of Pediatrics; 2Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, NC, USA; 3US EPA, RTP, NC, USA.

  2. Early Telegraphic News Dispatches: The Forerunner of the AP.

    ERIC Educational Resources Information Center

    Schwarzlose, Richard A.

    The origin of the Associated Press (AP) lies in the early cooperative news gathering efforts of the editors of several New York newspapers. As early as May 1846, these editors were "pooling" their energies in response to newly developed modes of communication--the wire and wireless telegraph and the trans-oceanic steamship mail services.…

  3. Tank 241AP104 Grab Sampling and Analysis Plan

    SciTech Connect

    TEMPLETON, A.M.

    2000-11-09

    This sampling and analysis plan (SAP) identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for samples obtained from tank 241-AP-104. The purpose of this sampling event is to obtain information about the characteristics of the contents of 241-AP-104 required to provide sample material to the Waste Treatment Contractor. Grab samples will be obtained from riser 001 to provide sufficient material for the chemical analyses and tests required to satisfy these data quality objectives and ICD-23. The 222-S Laboratory will receive samples; composite the samples; perform chemical analyses on composite samples; and provide samples to the Waste Treatment Contractor and the Process Chemistry Laboratory. The Process Chemistry Laboratory at the 222-S Laboratory Complex will perform process tests to evaluate the behavior of the 241-AP-104 waste undergoing the retrieval and treatment scenarios defined in the applicable DQOs. The Waste Treatment Contractor will perform process verification and waste form qualification tests. Requirements for analyses of samples originating in the L & H DQO process tests will be documented in the corresponding test plan (Person 2000) and are not within the scope of this SAP. This report provides the general methodology and procedures to be used in the preparation, retrieval, transport, analysis, and reporting of results from grab samples retrieved from tank 241-AP-104.

  4. The New AP Chemistry Exam: Its Rationale, Content, and Scoring

    ERIC Educational Resources Information Center

    Price, Paul D.; Kugel, Roger W.

    2014-01-01

    The 2013-2014 academic year marks the rollout of the redesigned advanced placement (AP) chemistry course and exam. There have been many questions as to why the course was redesigned and how the new examination will differ from its legacy version. In this article we give a brief overview of the legacy course and examine why a redesign occurred in…

  5. AP1000 Features Prevent Potential Containment Recirculation Screen Plugging

    SciTech Connect

    Andreychek, Timothy; Anderson, Richard; Schulz, Terry

    2004-07-01

    This paper presents the results of plant design development and evaluations that demonstrate that the AP1000 plant is not subject to potential containment recirculation screen plugging following a loss-of-coolant-accident (LOCA). Following a LOCA in a pressurized water reactor, it is necessary to recirculate water from the containment back into the reactor to maintain long term core cooling. The AP1000 utilizes passive safety systems to provide containment recirculation for long term core cooling following a LOCA. The AP1000 also has non-safety pumps which provide a backup means of providing recirculation. Screens are provided around the recirculation pipes to prevent debris from blocking recirculation flow and core cooling passages. Debris may be generated by the LOCA blowdown from insulation and coatings used inside containment. Even with effective cleanliness programs, there may be some resident debris such as dust and dirt. The potential for plugging the recirculation screens is a current PWR licensing issue. The AP1000 design provides inherent advantages with respect to the potential plugging of containment recirculation screens. These characteristics include prevention of fibrous debris generation, improved debris settling and improved recirculation screen design. Debris settling analysis demonstrates that failure of coatings does not result in debris being transported to the screens before it settles to the floor. Additional analysis also shows that the plant can tolerate conservative amounts of resident debris being transported to the screens. The AP1000 significantly reduces the probability of plugging the containment recirculation screens and significantly reduces inspection and maintenance of coatings used inside containment. (authors)

  6. New subsets of the antiphospholipid syndrome in 2006: "PRE-APS" (probable APS) and microangiopathic antiphospholipid syndromes ("MAPS").

    PubMed

    Asherson, Ronald A

    2006-12-01

    The concept of "probable" antiphospholipid syndrome (APS) is almost identical with several conditions which may presage the development of the APS with its major complications of large vessel thromboses resulting in deep vein occlusions in the lower limbs (DVT) particularly and strokes. These conditions comprising livedo reticularis, chorea, thrombocytopenia, fetal loss and valve lesions. These conditions, comprising livedo reticularis, chorea, thrombocytopenia, fetal loss and valve lesions may be followed, often years later by diagnosable APS. The issue whether these patients should be more aggressively treated on presentation in order to prevent the thrombotic complications. A new subset of the APS is proposed viz. microangiopathic antiphospholipid syndrome ("MAPS") comprising those patients presenting with thrombotic microangiopathy and demonstrable antiphospholipid antibodies who may share common although not identical provoking factors (e.g. infections, drugs), clinical manifestations and haematological manifestations (severe thrombocytopenia, hemolytic anaemia) and treatments viz. plasma exchange. Patients without large vessel occlusions may be included in the MAPS subset. These conditions include thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and the HELLP syndrome. Patients with catastrophic antiphospholipid syndrome (CAPS) who do not demonstrate large vessel occlusions also fall into this group. Disseminated intravascular coagulation (DIC) has also been reported with demonstrable antiphospholipid antibodies and also manifests severe thrombocytopenia and small vessel occlusions. It may cause problems in differential diagnosis.

  7. Aviation Safety Program: Weather Accident Prevention (WxAP) Development of WxAP System Architecture And Concepts of Operation

    NASA Technical Reports Server (NTRS)

    Grantier, David

    2003-01-01

    This paper presents viewgraphs on the development of the Weather Accident Prevention (WxAP) System architecture and Concept of Operation (CONOPS) activities. The topics include: 1) Background Information on System Architecture/CONOPS Activity; 2) Activity Work in Progress; and 3) Anticipated By-Products.

  8. El Maestro de Sala Regular de Clases Ante el Proceso de Inclusion del Nino Con Impedimento

    ERIC Educational Resources Information Center

    Rosa Morales, Awilda

    2012-01-01

    The purpose of this research was to describe the experiences of regular class elementary school teachers with the Puerto Rico Department of Education who have worked with handicapped children who have been integrated to the regular classroom. Five elementary level regular class teachers were selected in the northwest zone of Puerto Rico who during…

  9. The 50 kDa protein subunit of assembly polypeptide (AP) AP-2 adaptor from clathrin-coated vesicles is phosphorylated on threonine-156 by AP-1 and a soluble AP50 kinase which co-purifies with the assembly polypeptides.

    PubMed Central

    Pauloin, A; Thurieau, C

    1993-01-01

    AP50 is a subunit of the assembly polypeptide (AP) subclass AP-2 from bovine brain coated vesicles. It can be phosphorylated in vivo and in vitro on a threonine residue by means of the AP50 kinase activity associated with AP. We have undertaken an analysis of the amino acid sequence around the AP50 phosphorylation site. After phosphorylation in vitro of AP50 followed by tryptic cleavage, only one radioactive peptide was isolated following Mono-Q ion-exchange f.p.l.c. and reverse-phase h.p.l.c. The amino acid sequence of this peptide: Glu146-Glu-Gln-Ser-Gln-Ile-Thr-Ser-Gln-Val-Thr*-Gly-Gly-Ile-Gly-Tr p-Arg162, displayed two threonine residues. Analysis of the yield and radioactivity of the product from automated Edman degradation indicated that only Thr-156 was phosphorylated, reflecting the presence of a single phosphorylation site in AP50. AP phosphorylated the corresponding synthetic peptide on the same threonyl residue. We demonstrated that AP50 was a phosphorylation substrate unable to autophosphorylate. The enzyme involved in the AP50 phosphorylation was shown to be associated with AP-1 and with a soluble protein complex co-purified with APs but resolved from the latter by hydroxyapatite-column exclusion chromatography. This AP50 kinase activity corresponded to a 280 kDa protein complex according to gel-filtration data. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8257432

  10. Calcyon, a mammalian specific NEEP21 family member, interacts with adaptor protein complex 3 (AP-3) and regulates targeting of AP-3 cargoes.

    PubMed

    Muthusamy, Nagendran; Faundez, Victor; Bergson, Clare

    2012-10-01

    Calcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain and stimulates clathrin assembly and clathrin-mediated endocytosis. A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (μ) subunits interact with a YXXØ-type tyrosine motif located at residues 133-136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of μ3, and also impacted μ1 and μ2 binding to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP-3 suggesting that calcyon could regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and AP-3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4-kinase type II alpha (PI4KIIα), two well-defined AP-3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously described in AP-3 deficiencies. Altogether, our data suggest that calcyon directly interacts with μ3A and μ3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes.

  11. CALCYON, A MAMMALIAN SPECIFIC NEEP21 FAMILY MEMBER, INTERACTS WITH ADAPTOR PROTEIN COMPLEX 3 (AP-3) AND REGULATES TARGETING OF AP-3 CARGOES

    PubMed Central

    Muthusamy, Nagendran; Faundez, Victor; Bergson, Clare

    2013-01-01

    Calcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain (CLC) and stimulates clathrin assembly and clathrin mediated endocytosis (CME). A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (µ) subunits interact with a YXXØ-type tyrosine motif located at residues 133–136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of µ3, and also impacted µ1 and µ2 binding but to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null-alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP-3 suggesting that calcyon could regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and AP-3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4-kinase type II alpha (PI4KIIα), two well-defined AP-3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously described in AP-3 deficiencies. Altogether, our data suggest that calcyon directly interacts with µ3A and µ3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes. PMID:22650988

  12. MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state

    PubMed Central

    Frottin, Frédéric; Bienvenut, Willy V.; Bignon, Jérôme; Jacquet, Eric; Jacome, Alvaro Sebastian Vaca; Van Dorsselaer, Alain; Cianferani, Sarah; Carapito, Christine; Meinnel, Thierry; Giglione, Carmela

    2016-01-01

    Fumagillin and its derivatives are therapeutically useful because they can decrease cancer progression. The specific molecular target of fumagillin is methionine aminopeptidase 2 (MetAP2), one of the two MetAPs present in the cytosol. MetAPs catalyze N-terminal methionine excision (NME), an essential pathway of cotranslational protein maturation. To date, it remains unclear the respective contribution of MetAP1 and MetAP2 to the NME process in vivo and why MetAP2 inhibition causes cell cycle arrest only in a subset of cells. Here, we performed a global characterization of the N-terminal methionine excision pathway and the inhibition of MetAP2 by fumagillin in a number of lines, including cancer cell lines. Large-scale N-terminus profiling in cells responsive and unresponsive to fumagillin treatment revealed that both MetAPs were required in vivo for M[VT]X-targets and, possibly, for lower-level M[G]X-targets. Interestingly, we found that the responsiveness of the cell lines to fumagillin was correlated with the ability of the cells to modulate their glutathione homeostasis. Indeed, alterations to glutathione status were observed in fumagillin-sensitive cells but not in cells unresponsive to this agent. Proteo-transcriptomic analyses revealed that both MetAP1 and MetAP2 accumulated in a cell-specific manner and that cell sensitivity to fumagillin was related to the levels of these MetAPs, particularly MetAP1. We suggest that MetAP1 levels could be routinely checked in several types of tumor and used as a prognostic marker for predicting the response to treatments inhibiting MetAP2. PMID:27542228

  13. Airborne Precision Spacing (APS) Dependent Parallel Arrivals (DPA)

    NASA Technical Reports Server (NTRS)

    Smith, Colin L.

    2012-01-01

    The Airborne Precision Spacing (APS) team at the NASA Langley Research Center (LaRC) has been developing a concept of operations to extend the current APS concept to support dependent approaches to parallel or converging runways along with the required pilot and controller procedures and pilot interfaces. A staggered operations capability for the Airborne Spacing for Terminal Arrival Routes (ASTAR) tool was developed and designated as ASTAR10. ASTAR10 has reached a sufficient level of maturity to be validated and tested through a fast-time simulation. The purpose of the experiment was to identify and resolve any remaining issues in the ASTAR10 algorithm, as well as put the concept of operations through a practical test.

  14. Fabrication techniques for septum magnets at the APS.

    SciTech Connect

    Jaski, M.; Thompson, K.; Kim, S.; Friedsam, H.; Toter, W.; Humbert, J.

    2002-09-16

    The design, construction, and installation of pulsed septum magnets for particle accelerators presents many challenges for the magnet engineer. Issues associated with magnet core structure design, component alignment, weldment design, and electrical insulation choices are among those requiring careful attention. The designs of the six septum magnets required for the APS facility have evolved since operation began in 1996. Improvements in the designs have provided better injection/extraction performance parameters and extended the machine reliability to meet the requirements of a world-class, third-generation synchrotron radiation facility. Details of the techniques used to address issues involved in producing septum magnets at the APS are described here to aid magnet engineers in the fabrication of future septum magnets.

  15. Comparison of the APS and UGIMAG Helmholtz coil systems

    SciTech Connect

    Carnegie, D.W.

    1994-05-09

    UGIMAG is manufacturing the NdFeB permanent magnet blocks to be used in undulator A now being assembled by STI Optronics. The authors would like to be able to compare measurements made at the plant with those made at ANL and potentially with those made at the STI facility. Since there are no permanent magnet standard samples, measurement systems are compared by trading sets of magnets set aside as standards. APS has ten NdFeB permanent magnet blocks supplied by Sumitomo that they use to make these comparisons. These magnet samples have been extensively measured on the APS system. The data include the three vector components of the total magnetic dipole moment of the blocks as well as the spherical coordinates of the vector.

  16. Status of APS 1-Mwe Parabolic Trough Project

    SciTech Connect

    Canada, S.; Brosseau, D.; Kolb, G.; Moore, L.; Cable, R.; Price, H.

    2005-11-01

    Arizona Public Service (APS) is currently installing new power facilities to generate a portion of its electricity from solar resources that will satisfy its obligation under the Arizona Environmental Portfolio Standard (EPS). During FY04, APS began construction on a 1-MWe parabolic trough concentrating solar power plant. This plant represents the first parabolic trough plant to begin construction since 1991. Site preparation and construction activities continued throughout much of FY05, and startup activities are planned for Fall 2005 (with completion early in FY06). The plant will be the first commercial deployment of the Solargenix parabolic trough collector technology developed under contract to the National Renewable Energy Laboratory. The plant will use an organic Rankine cycle (ORC) power plant, provided by Ormat. The ORC power plant is much simpler than the conventional steam Rankine cycle plant and allows unattended operation of the facility.

  17. Time resolved spectroscopy of the cool Ap star HD 213637*

    NASA Astrophysics Data System (ADS)

    Elkin, V. G.; Kurtz, D. W.; Mathys, G.

    2015-02-01

    We present an analysis of high time resolution spectra of the chemically peculiar Ap star HD 213637. The star shows rapid radial velocity variations with a period close to the photometric pulsation period. Radial velocity pulsation amplitudes vary significantly for different rare earth elements. The highest pulsation amplitudes belong to lines of Tb III (˜360 m s-1), Pr II (˜250 m s-1) and Pr III (˜230 m s-1). We did not detect any pulsations from spectral lines of Eu II and in Hα, in contrast to many other roAp stars. We also did not find radial velocity pulsations using spectral lines of other chemical elements, including Mg, Si, Ca, Sc, Cr, Fe, Ni, Y and Ba. There are phase shifts between the maxima of pulsation amplitudes of different rare earth elements and ions, which is evidence of an outwardly running magneto-acoustic wave propagating through the upper stellar atmosphere.

  18. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-30

    because they are readily available, relatively inexpensive, and require little training. Israel’s experiences with RPGs and ATGMs in the 2006 Israel...safe enough for operational use, the benefits of MAPS relative to non-developmental efforts, MAPS’ impacts on NDI APS performance and costs, the Army’s...APSs Effective and Safe Enough for Operational Use? .............................. 24 What are the Benefits of MAPS Relative to Non-Developmental

  19. Diffusion and Settling in Ap/Bp Stars

    SciTech Connect

    Turcotte, S

    2003-04-09

    Ap/Bp stars are magnetic chemically peculiar early A and late B type stars of the main sequence. They exhibit peculiar surface abundance anomalies that are thought to be the result of gravitational settling and radiative levitation. The physics of diffusion in these stars are reviewed briefly and some model predictions are discussed. While models reproduce some observations reasonably well, more work is needed before the behavior of diffusing elements in a complex magnetic field is fully understood.

  20. Electron-cloud measurements and simulations for the APS

    SciTech Connect

    Furman, M.A.; Pivi, M.; Harkay, K.C.; Rosenberg, R.A.

    2001-06-26

    We compare experimental results with simulations of the electron cloud effect induced by a positron beam at the APS synchrotron light source at ANL, where the electron cloud effect has been observed and measured with dedicated probes. We find good agreement between simulations and measurements for reasonable values of certain secondary electron yield (SEY) parameters, most of which were extracted from recent bench measurements at SLAC.

  1. Heterologous expression of ApGSMT2 and ApDMT2 genes from Aphanothece halophytica enhanced drought tolerance in transgenic tobacco.

    PubMed

    He, Ying; He, Chunmei; Li, Lihua; Liu, Zhili; Yang, Aifang; Zhang, Juren

    2011-01-01

    The glycine-methylation biosynthetic pathway of glycinebetaine (GB) has been investigated, but only a few studies on GB accumulation in transgenic higher plants have utilized this pathway. In this study, two methyltransferase genes named ApGSMT2 and ApDMT2, encoding proteins catalyzing GB biosynthesis from glycine, were cloned from a relative strain of Aphanothece halophytica. The potential roles of ApGSMT2 and ApDMT2 in GB synthesis were first examined in transgenic Escherichia coli, which had increased levels of GB and improved salt tolerance. Then ApGSMT2 and ApDMT2 were transferred into tobacco. Compared with transgenic tobacco expressing betA, transgenic tobacco co-expressing ApGSMT2 and ApDMT2 accumulated more GB and exhibited enhanced drought resistance with better germination performance, higher relative water content, less cell membrane damage and better photosynthetic capacity under drought stress. We concluded that the ApGSMT2 and ApDMT2 genes cloned in this study will be very useful for engineering GB-accumulating transgenic plants with enhanced drought resistance.

  2. Determination of floral organ identity by Arabidopsis MADS domain homeotic proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity.

    PubMed Central

    Riechmann, J L; Meyerowitz, E M

    1997-01-01

    The MADS domain homeotic proteins APETALA1 (AP1), APETALA3 (AP3), PISTILLATA (PI), and AGAMOUS (AG) combinatorially specify the identity of Arabidopsis floral organs. AP1/AP1, AG/AG, and AP3/PI dimers bind to similar CArG box sequences; thus, differences in DNA-binding specificity among these proteins do not seem to be the origin of their distinct organ identity properties. To assess the overall contribution that specific DNA binding could make to their biological specificity, we have generated chimeric genes in which the amino-terminal half of the MADS domain of AP1, AP3, PI, and AG was substituted by the corresponding sequences of human SRF and MEF2A proteins. In vitro DNA-binding assays reveal that the chimeric proteins acquired the respective, and distinct, DNA-binding specificity of SRF or MEF2A. However, ectopic expression of the chimeric genes reproduces the dominant gain-of-function phenotypes exhibited by plants ectopically expressing the corresponding Arabidopsis wild-type genes. In addition, both the SRF and MEF2 chimeric genes can complement the pertinent ap1-1, ap3-3, pi-1, or ag-3 mutations to a degree similar to that of AP1, AP3, PI, and AG when expressed under the control of the same promoter. These results indicate that determination of floral organ identity by the MADS domain homeotic proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity. In addition, the DNA-binding experiments show that either one of the two MADS domains of a dimer can be sufficient to confer a particular DNA-binding specificity to the complex and that sequences outside the amino-terminal basic region of the MADS domain can, in some cases, contribute to the DNA-binding specificity of the proteins. Images PMID:9243505

  3. Mineralocorticoid Receptor (MR) trans-Activation of Inflammatory AP-1 Signaling: DEPENDENCE ON DNA SEQUENCE, MR CONFORMATION, AND AP-1 FAMILY MEMBER EXPRESSION.

    PubMed

    Dougherty, Edward J; Elinoff, Jason M; Ferreyra, Gabriela A; Hou, Angela; Cai, Rongman; Sun, Junfeng; Blaine, Kevin P; Wang, Shuibang; Danner, Robert L

    2016-11-04

    Glucocorticoids are commonly used to treat inflammatory disorders. The glucocorticoid receptor (GR) can tether to inflammatory transcription factor complexes, such as NFκB and AP-1, and trans-repress the transcription of cytokines, chemokines, and adhesion molecules. In contrast, aldosterone and the mineralocorticoid receptor (MR) primarily promote cardiovascular inflammation by incompletely understood mechanisms. Although MR has been shown to weakly repress NFκB, its role in modulating AP-1 has not been established. Here, the effects of GR and MR on NFκB and AP-1 signaling were directly compared using a variety of ligands, two different AP-1 consensus sequences, GR and MR DNA-binding domain mutants, and siRNA knockdown or overexpression of core AP-1 family members. Both GR and MR repressed an NFκB reporter without influencing p65 or p50 binding to DNA. Likewise, neither GR nor MR affected AP-1 binding, but repression or activation of AP-1 reporters occurred in a ligand-, AP-1 consensus sequence-, and AP-1 family member-specific manner. Notably, aldosterone interactions with both GR and MR demonstrated a potential to activate AP-1. DNA-binding domain mutations that eliminated the ability of GR and MR to cis-activate a hormone response element-driven reporter variably affected the strength and polarity of these responses. Importantly, MR modulation of NFκB and AP-1 signaling was consistent with a trans-mechanism, and AP-1 effects were confirmed for specific gene targets in primary human cells. Steroid nuclear receptor trans-effects on inflammatory signaling are context-dependent and influenced by nuclear receptor conformation, DNA sequence, and the expression of heterologous binding partners. Aldosterone activation of AP-1 may contribute to its proinflammatory effects in the vasculature.

  4. ATP6AP2 — EDRN Public Portal

    Cancer.gov

    ATP6AP2 functions as a renin and prorenin cellular receptor. It may mediate renin-dependent cellular responses by activating ERK1 and ERK2. By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, it may also play a role in the renin-angiotensin system (RAS). ATP6AP2 is expressed in brain, heart, placenta, liver, kidney and pancreas; it is barely detectable in lung and skeletal muscles. In the kidney cortex it is restricted to the mesangium of glomeruli. In the coronary and kidney artery it is expressed in the subendothelium, associated to smooth muscles where it colocalizes with REN. It is expressed in vascular structures and by syncytiotrophoblast cells in the mature fetal placenta. Defects in ATP6AP2 are a cause of mental retardation X-linked with epilepsy (MRXE). MRXE is a syndromic mental retardation. Patients manifest mild to moderate mental retardation associated with epilepsy, delays in motor milestones and speech acquisition in infancy.

  5. A Semi-automated Abundance Survey of Ap Stars

    NASA Astrophysics Data System (ADS)

    Hall, Martin P.; Kurtz, Don; Elkin, Vladimir; Bruntt, Hans

    2015-08-01

    We have carried out an abundance analysis on the high-resolution spectra of approximately 350 Ap stars collected between 2007 and 2010 on the FEROS Echelle (Fibre-led, Extended Range, Echelle ) spectrograph housed at the 2.2-m telescope at European Southern Observatory at La Silla, Chile. We employed the VWA package (vsin I, wavelength shift, abundance analysis) for preliminary selection of spectral lines, and a semi-automated set of routines which we developed in the programming language IDL, to calculate the equivalent widths and abundances of ions of Iron and the rare earth elements Neodymium and Praseodymium using the WIDTH program and NEMO model atmospheres. Initial results are presented, which reinforce the correlation between iron abundance and effective temperature, from an over-abundance in the late Bp stars, to under-abundant in the early F stars. Results also suggest that the disequilibrium in abundances of the first and second ionisation stages of these ions in the rapidly oscillating Ap (roAp) stars may a consequence of the relatively cool temperatures of those stars, rather than a signature of pulsation.

  6. AP4 is required for mitogen- and c-MYC-induced cell cycle progression

    PubMed Central

    Jackstadt, Rene; Hermeking, Heiko

    2014-01-01

    AP4 represents a c-MYC-inducible bHLH-LZ transcription factor, which displays elevated expression in many types of tumors. We found that serum-starved AP4-deficient mouse embryo fibroblasts (MEFs) were unable to resume proliferation and showed a delayed S-phase entry after restimulation. Furthermore, they accumulated as tetraploid cells due to a cytokinesis defect. In addition, AP4 was required for c-MYC-induced cell cycle re-entry. AP4-deficient MEFs displayed decreased expression of CDK2 (cyclin-dependent kinase 2), which we characterized as a conserved and direct AP4 target. Activation of an AP4 estrogen receptor fusion protein (AP4-ER) enhanced proliferation of human diploid fibroblasts in a CDK2-dependent manner. However, in contrast to c-MYC-ER, AP4-ER activation was not sufficient to induce cell cycle re-entry or apoptosis in serum-starved MEFs. AP4-deficiency was accompanied by increased spontaneous and c-MYC-induced DNA damage in MEFs. Furthermore, c-MYC-induced apoptosis was decreased in AP4-deficient MEFs, suggesting that induction of apoptosis by c-MYC is linked to its ability to activate AP4 and thereby cell cycle progression. Taken together, these results indicate that AP4 is a central mediator and coordinator of cell cycle progression in response to mitogenic signals and c-MYC activation. Therefore, inhibition of AP4 function may represent a therapeutic approach to block tumor cell proliferation. PMID:25261373

  7. Alejarse como proceso social: niños y ancianos «abandonados» en Ayacucho1

    PubMed Central

    Leinaweaver, Jessaca

    2013-01-01

    En investigaciones previas sobre el acogimiento familiar y la adopción en Ayacucho, se ha podido descubrir cómo los ayacuchanos adquieren y producen relaciones sociales. Mientras negocian creativamente los discursos y espacios construidos simultáneamente por instituciones, comunidades, y estructuras sociales, van adquiriendo nuevas formas de relacionarse. Este artículo discute el proceso opuesto: el deshacerse de relaciones de parentesco, y el proceso social del abandono o alejamiento. Cuando se aleja a una persona de su familia o su comunidad, los que se quedan en ella llegan a entenderse como ciertos tipos de personas. En los estudios de caso discutidos aquí, recopilados a través de una detallada y cuidadosa observación participante y de entrevistas etnográficas grabadas entre 2001 y 2007, se puede ver cómo, después de un alejamiento social, los individuos que alejan se reinterpretan como sujetos que se encuentran superándose o volviéndose modernos, o bien sacrificándose. PMID:25177044

  8. The Adolescent Novel in AP English: A Response to Patricia Spencer.

    ERIC Educational Resources Information Center

    McGee, Tim

    1992-01-01

    Discusses the absence of adolescent literature in Advanced Placement (AP) English classes. Describes how a class of AP students and their teacher benefited from reading Robert Cormier's "The Chocolate War." (PRA)

  9. The Relationship between AP[R] Exam Performance and College Outcomes. Research Report No. 2009-4

    ERIC Educational Resources Information Center

    Mattern, Krista D.; Shaw, Emily J.; Xiong, Xinhui

    2009-01-01

    This study focused on the relationship between students' Advanced Placement Program[R] (AP[R]) performance in AP English Language, Biology, Calculus, and U.S. History, and their subsequent college success. For each AP Exam studied, students were divided into three groups according to their AP Exam performance (no AP Exam taken, score of 1 or 2,…

  10. The mean magnetic field modulus of AP stars

    NASA Astrophysics Data System (ADS)

    Mathys, G.; Hubrig, S.; Landstreet, J. D.; Lanz, T.; Manfroid, J.

    1997-06-01

    We present new measurements of the mean magnetic field modulus of a sample of Ap stars with spectral lines resolved into magnetically split components. We report the discovery of 16 new stars having this property. This brings the total number of such stars known to 42. We have performed more than 750 measurements of the mean field modulus of 40 of these 42 stars, between May 1988 and August 1995. The best of them have an estimated accuracy of 25 - 30 G. The availability of such a large number of measurements allows us to discuss for the first time the distribution of the field modulus intensities. A most intriguing result is the apparent existence of a sharp cutoff at the low end of this distribution, since no star with a field modulus (averaged over the rotation period) smaller than 2.8 kG has been found in this study. For more than one third of the studied stars, enough field determinations well distributed throughout the stellar rotation cycle have been achieved to allow us to characterize at least to some extent the variations of the field modulus. These variations are often significantly anharmonic, and it is not unusual for their extrema not to coincide in phase with the extrema of the longitudinal field (for the few stars for which enough data exist about the latter). This, together with considerations on the distribution of the relative amplitude of variation of the studied stars, supports the recently emerging evidence for markedly non-dipolar geometry and fine structure of the magnetic fields of most Ap stars. New or improved determinations of the rotation periods of 9 Ap stars have been achieved from the analysis of the variations of their mean magnetic field modulus. Tentative values of the period have been derived for 5 additional stars, and lower limits have been established for 10 stars. The shortest definite rotation period of an Ap star with magnetically resolved lines is 3.4 deg, while those stars that rotate slowest appear to have periods in

  11. NRC confirmatory AP600 safety system phase I testing in the ROSA/AP600 test facility

    SciTech Connect

    Rhee, G.S.; Kukita, Yutaka; Schultz, R.R.

    1996-03-01

    The NRC confirmatory phase I testing for the AP600 safety systems has been completed in the modified ROSA (Rig of Safety Assessment) test facility located at the Japan Atomic Energy Research Institute (JAERI) campus in Tokai, Japan. The test matrix included a variety of accident scenarios covering both design and beyond-design basis accidents. The test results indicate the AP600 safety systems as reflected in ROSA appear to perform as designed and there is no danger of core heatup for the accident scenarios investigated. In addition, no detrimental system interactions nor adverse effects of non-safety systems on the safety system functions were identified. However, three phenomena of interest have been identified for further examination to determine whether they are relevant to the AP600 plant. Those three phenomena are: (1) a potential for water hammer caused by rapid condensation which may occur following the actuation of the automatic depressurization system (ADS), (2) a large thermal gradient in the cold leg pipe where cooled water returns from the passive residual heat removal system and forms a thermally stratified layer, and (3) system-wide oscillations initiating following the ADS stage 4 actuation and persisting until the liquid in the pressurizer drains and steam generation in the core becomes insignificant.

  12. AP Studio Art as an Enabling Constraint for Secondary Art Education

    ERIC Educational Resources Information Center

    Graham, Mark A.

    2009-01-01

    Advanced Placement (AP) Studio Art is an influential force in secondary art education as is evident in the 31,800 portfolios submitted for review in 2008. From the perspectives of a high school educator and AP Reader, this author has observed how the constraints of the AP program can be used to generate support for high school art programs and…

  13. Building Reading, Writing and Analysis in the AP U.S. History Classroom

    ERIC Educational Resources Information Center

    Heller, Stephen; Stacy, Jason

    2013-01-01

    The building of historical thinking skills has historically been a lonely endeavor for AP U.S. history teachers. Many often generate their own pedagogy, perhaps modified from an AP workshop or generally gleaned from released exam essay questions. However, as currently scheduled, in 2014, the AP U.S. history exam will undergo a redesign that will…

  14. The U.S. Government's Assistance to the AP's World-Wide Expansion: 1912-1948.

    ERIC Educational Resources Information Center

    Renaud-Komiya, Jean-Luc

    A study of the extent of the diplomatic and commercial assistance provided by the United States government to the Associated Press (AP) from 1912 to 1948 shows AP's manager, Kent Cooper, to be less a champion of the free press than an efficient captain of industry in expanding AP influence across the globe. Early in the twentieth century, British,…

  15. Transcription factor AP-2α regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression.

    PubMed

    Ding, Xiaofeng; Yang, Zijian; Zhou, Fangliang; Wang, Fangmei; Li, Xinxin; Chen, Cheng; Li, Xiaofeng; Hu, Xiang; Xiang, Shuanglin; Zhang, Jian

    2013-08-01

    Transcription factor AP-2α mediates transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. In the current study, we identified Hoxa7, Hoxa9 and Hox cofactor Meis1 as AP-2α target genes, which are involved in myeloid leukemogenesis. Luciferase reporter assays revealed that overexpression of AP-2α activated transcription activities of Hoxa7, Hoxa9 and Meis1, whereas siRNA of AP-2α inhibited their transcription activities. We found that AP-2 binding sites in regulatory regions of three genes activated their transcription by mutant analysis and AP-2α could interact with AP-2 binding sites in vivo by chromatin immunoprecipitation (ChIP). Further results showed that the AP-2α shRNA efficiently inhibited mRNA and protein levels of Hoxa7, Hoxa9 and Meis1 in AML cell lines U937 and HL60. Moreover, decreased expression of AP-2α resulted in a significant reduction in the growth and proliferation of AML cells in vitro. Remarkably, AP-2α knockdown leukemia cells exhibit decreased tumorigenicity in vivo compared with controls. Finally, AP-2α and target genes in clinical acute myeloid leukemia samples of M5b subtype revealed variable expression levels and broadly paralleled expression. These data support a role of AP-2α in mediating the expression of Hoxa genes in acute myeloid leukemia to influence the proliferation and cell survival.

  16. PsAP2 an AP2/ERF family transcription factor from Papaver somniferum enhances abiotic and biotic stress tolerance in transgenic tobacco.

    PubMed

    Mishra, Sonal; Phukan, Ujjal J; Tripathi, Vineeta; Singh, Dhananjay K; Luqman, Suaib; Shukla, Rakesh Kumar

    2015-09-01

    The AP2/ERFs are one of the most important family of transcription factors which regulate multiple responses like stress, metabolism and development in plants. We isolated PsAP2 a novel AP2/ERF from Papaver somniferum which was highly upregulated in response to wounding followed by ethylene, methyl jasmonate and ABA treatment. PsAP2 showed specific binding with both DRE and GCC box elements and it was able to transactivate the reporter genes in yeast. PsAP2 overexpressing transgenic tobacco plants exhibited enhanced tolerance towards both abiotic and biotic stresses . Real time transcript expression analysis showed constitutive upregulation of tobacco Alternative oxidase1a and Myo-inositol-1-phosphate synthase in PsAP2 overexpressing tobacco plants. Further, PsAP2 showed interaction with NtAOX1a promoter in vitro, it also specifically activated the NtAOX1a promoter in yeast and tobacco BY2 cells. The silencing of PsAP2 using VIGS lead to significant reduction in the AOX1 level in P. somniferum. Taken together PsAP2 can directly bind and transcriptionally activate NtAOX1a and its overexpression in tobacco imparted increased tolerance towards both abiotic and biotic stress.

  17. ApCPEB4, a non-prion domain containing homolog of ApCPEB, is involved in the initiation of long-term facilitation.

    PubMed

    Lee, Seung-Hee; Shim, Jaehoon; Cheong, Ye-Hwang; Choi, Sun-Lim; Jun, Yong-Woo; Lee, Sue-Hyun; Chae, Yeon-Su; Han, Jin-Hee; Lee, Yong-Seok; Lee, Jin-A; Lim, Chae-Seok; Si, Kausik; Kassabov, Stefan; Antonov, Igor; Kandel, Eric R; Kaang, Bong-Kiun; Jang, Deok-Jin

    2016-10-22

    Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the threshold of the formation of LTF. Thus, our findings suggest that the two different forms of CPEBs play distinct roles in LTF; ApCPEB is required for maintenance of LTF, whereas the ApCPEB4, which lacks a prion-like domain, is required for the initiation of LTF.

  18. Structural characterization of the N-terminal mineral modification domains from the molluscan crystal-modulating biomineralization proteins, AP7 and AP24.

    PubMed

    Wustman, Brandon A; Morse, Daniel E; Evans, John Spencer

    2004-08-05

    The AP7 and AP24 proteins represent a class of mineral-interaction polypeptides that are found in the aragonite-containing nacre layer of mollusk shell (H. rufescens). These proteins have been shown to preferentially interfere with calcium carbonate mineral growth in vitro. It is believed that both proteins play an important role in aragonite polymorph selection in the mollusk shell. Previously, we demonstrated the 1-30 amino acid (AA) N-terminal sequences of AP7 and AP24 represent mineral interaction/modification domains in both proteins, as evidenced by their ability to frustrate calcium carbonate crystal growth at step edge regions. In this present report, using free N-terminal, C(alpha)-amide "capped" synthetic polypeptides representing the 1-30 AA regions of AP7 (AP7-1 polypeptide) and AP24 (AP24-1 polypeptide) and NMR spectroscopy, we confirm that both N-terminal sequences possess putative Ca (II) interaction polyanionic sequence regions (2 x -DD- in AP7-1, -DDDED- in AP24-1) that are random coil-like in structure. However, with regard to the remaining sequences regions, each polypeptide features unique structural differences. AP7-1 possesses an extended beta-strand or polyproline type II-like structure within the A11-M10, S12-V13, and S28-I27 sequence regions, with the remaining sequence regions adopting a random-coil-like structure, a trait common to other polyelectrolyte mineral-associated polypeptide sequences. Conversely, AP24-1 possesses random coil-like structure within A1-S9 and Q14-N16 sequence regions, and evidence for turn-like, bend, or loop conformation within the G10-N13, Q17-N24, and M29-F30 sequence regions, similar to the structures identified within the putative elastomeric proteins Lustrin A and sea urchin spicule matrix proteins. The similarities and differences in AP7 and AP24 N-terminal domain structure are discussed with regard to joint AP7-AP24 protein modification of calcium carbonate growth.

  19. Contribución al flujo infrarrojo de las estrellas Be de la recombinación dielectrónica del MgII

    NASA Astrophysics Data System (ADS)

    Cruzado, A.; di Rocco, H.; Ringuelet, A.

    Para evaluar la contribución del proceso de recombinación dielectrónica del átomo de MgII al exceso de flujo infrarrojo observado en las estrellas Be, calculamos la energía emitida en las líneas originadas por este proceso. Se evaluaron los efectos de las condiciones físicas del medio, como la temperatura electrónica y la densidad electrónica, sobre el flujo emitido. Se consideró también la influencia de una posible opacidad.

  20. Ku antigen displays the AP lyase activity on a certain type of duplex DNA.

    PubMed

    Kosova, Anastasiya A; Khodyreva, Svetlana N; Lavrik, Olga I

    2016-09-01

    In the search for proteins reactive to apurinic/apyrimidinic (AP) sites, it has been earlier found that proteins of human cell extracts formed the Schiff-base-dependent covalent adduct with an apparent molecular mass of 100kDa with a partial DNA duplex containing an AP site and 5'- and 3'-protruding ends (DDE-AP DNA). The adduct of such electrophoretic mobility was characteristic of only DDE-AP DNA (Ilina et al., Biochem. Biophys. Acta 1784 (2008) 1777-1785). The protein in this unusual adduct was identified as the Ku80 subunit of Ku antigen by peptide mass mapping based on MALDI-TOF MS data (Kosova et al., Biopolym. Cell 30 (2014) 42-46). Here we studied the interaction of Ku with DDE-AP DNA in details. Purified Ku (the Ku80 subunit) was shown to form the 100-kDa adduct highly specific for AP DNA with a certain length of protruding ends, base opposite the AP site and AP site location. Ku is capable of AP site cleavage in DDE-AP DNA unlike in analogous AP DNA with blunt ends. Ku cleaves AP sites via β-elimination and prefers apurinic sites over apyrimidinic ones. The AP site in DDE-DNA can be repaired in an apurinic/apyrimidinic endonuclease-independent manner via the successive action of Ku (cleavage of the AP site), tyrosyl-DNA phosphodiesterase 1 (removal of the 3'-deoxyribose residue), polynucleotide kinase 3'-phosphatase (removal of the 3'-phosphate), DNA polymerase β (incorporation of dNMP), and DNA ligase (sealing the nick). These results provide a new insight into the role of Ku in the repair of AP sites.

  1. The AE9/AP9 Next Generation Radiation Specification Models

    NASA Astrophysics Data System (ADS)

    O'Brien, Paul; Ginet, Gregory; Huston, Stuart; Byers, David

    A significant effort is under way to develop the next-generation trapped proton and electron models for satellite design, AP-9 and AE-9, respectively. The primary objectives of the effort are to 1) improve the overall accuracy of the models; 2) provide indicators of the uncertainty in the model due to natural variability and instrument uncertainty; 3) cover a broad energy range including hot plasma, relativistic electrons and highly energetic protons; and 4) provide complete spatial coverage. In this paper we will present background, demonstration and initial feedback from a limited-release beta version of the model.

  2. Ethernet ring protection with managed FDB using APS payload

    NASA Astrophysics Data System (ADS)

    Im, Jinsung; Ryoo, Jeong-dong; Joo, Bheom Soon; Rhee, J.-K. Kevin

    2007-11-01

    Ethernet ring protection (ERP) is a new technology based on OAM (operations, administration, and maintenance) being standardized by the ITU-T G.8032 working group. In this paper, we present the recent development of Ethernet ring protection which is called FDB (filtering database) flush scheme and propose a new Ethernet ring protection technique introducing a managed FDB using APS to deliver information how to fix FDB selectively. We discuss the current development of the ERP technology at ITU-T and performance comparisons between different proposals.

  3. H-beta line variability in magnetic Ap stars. I

    NASA Technical Reports Server (NTRS)

    Madej, J.; Jahn, K.; Stepien, K.

    1984-01-01

    Preliminary results of photometric measurements of H-beta in several Ap stars are presented. Periodic variations are found certainly in Theta Aur and Alpha (2) CVn, and possibly in Phi Dra. For the other stars upper limits for variations of H-beta are determined. Observed amplitudes are transformed into variations of equivalent width assuming specific profile variations. The results show that variations of equivalent width of H-beta in the stars investigated are of the order of 10 percent or less.

  4. Higher-order modes in the APS storage ring waveguides

    SciTech Connect

    Brauer, S.O.; Kustom, R.L.

    1993-07-01

    Twelve higher-order modes (HOMs) in the single-cell accelerating cavities for the Advanced Photon Source (APS) storage ring were calculated to have complex impedances that will cause coupled-bunched instabilities near or below the 300mA positron current which is the design goal. Some of these modes couple, through the coupling loop, from the storage ring cavity into the waveguide. This study investigates the transmission of these modes from the cavity into the waveguide. The standing wave ratio (VSWR) of a WR2300 hybrid waveguide component has been measured at each HOM frequency, and its effect on the transmitted modes in the waveguide is studied.

  5. Multilayer growth in the APS rotary deposition system.

    SciTech Connect

    Conley, R.; Liu, C.; Kewish, C.M.; Macrander, A.T.; Morawe, C.; X-Ray Science Division; European Synchrotron Radiation Facility

    2007-01-01

    We report our progress in the growth of periodic and depth-graded multilayers in the APS rotary deposition system, a machine designed for fabrication of films tens of microns thick with thousands of layers. A computational method was employed to design depth-graded multilayers for use as wide-angular bandpass reflective optics. We present experimental results for a 154-layer WSi{sub 2}/Si multilayer system with bilayer thickness ranging from 2.2 nm to 5.5 nm that closely match theoretical flat-top reflectivity predictions of 9.8% from 15.6 mrad to 23.3 mrad at 8 keV.

  6. Operation of the APS photoinjector drive laser system.

    SciTech Connect

    Li, Y.; Accelerator Systems Division

    2008-08-04

    The APS photoinjector drive laser system has been in operation since 1999 and is achieving a performance level exceeding the requirement of stable operation of the LEUTL FEL system. One remarkable number is the UV energy stability of better than 2% rms, sometimes less than 1% rms. This report summarizes the operation experience of the laser system and the improvements made along the way. We also outline the route of upgrade of the system and some frontier laser research and development opportunities in ultrabright electron beam generation.

  7. Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx.

    PubMed

    Chernock, Rebecca D; Wang, Xiaowei; Gao, Ge; Lewis, James S; Zhang, Qin; Thorstad, Wade L; El-Mofty, Samir K

    2013-02-01

    Although a strong etiologic relationship between human papillomavirus (HPV) and a majority of oropharyngeal squamous cell carcinomas has been established, the role of HPV in non-oropharyngeal head and neck carcinomas is much less clear. Here, we investigated the prevalence and clinicopathologic significance of HPV and its reported biomarkers, CDKN2A(p16) and CDKN1A(p21), in laryngeal squamous cell carcinomas in patients treated either with primary surgery and postoperative radiation or with definitive radiation-based therapy. Nearly all of 76 tumors were keratinizing and none displayed the nonkeratinizing morphology that is typically associated with HPV infection in the oropharynx. However, CDKN2A(p16) immunohistochemistry was positive in 21 cases (28%) and CDKN1A(p21) in 34 (45%). CDKN2A(p16) and CDKN1A(p21) status strongly correlated with each other (P=0.0038). Yet, only four cases were HPV positive by DNA in situ hybridization or by reverse transcriptase PCR E6/E7 mRNA (all four were CDKN2A(p16) and CDKN1A(p21) positive). Unexpectedly, 9 additional tumors out of 20 CDKN2A(p16) positive cases harbored high-risk HPV DNA by PCR. For further investigation of this unexpected result, in situ hybridization for E6/E7 mRNA was performed on these nine cases and all were negative, confirming the absence of transcriptionally active virus. Patients with CDKN1A(p21)-positive tumors did have better overall survival (69% at 3 years) than those with CDKN1A(p21)-negative tumors (51% at 3 years) (P=0.045). There was also a strong trend towards better overall survival in the CDKN2A(p16)-positive group (P=0.058). Thus, it appears that the role of HPV is more complex in the larynx than in the oropharynx, and that CDKN2A(p16) and CDKN1A(p21) expression may not reflect HPV-driven tumors in most cases. Because of this, CDKN2A(p16) should not be used as a definitive surrogate marker of HPV-driven tumors in the larynx.

  8. NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton

    PubMed Central

    Ha, Van Thai; Beak, Heung Soo; Kim, Eunji; Baek, Kwang-Soo; Hossen, Muhammad Jahangir; Yang, Woo Seok; Kim, Yong; Joo, Yung Hyup; Lee, Chang Seok; Choi, Joonho; Shin, Hong-Ju; Hong, Sungyoul; Shin, Song Seok

    2014-01-01

    AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation. PMID:25386046

  9. Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA.

    PubMed

    Redrejo-Rodríguez, Modesto; Vigouroux, Armelle; Mursalimov, Aibek; Grin, Inga; Alili, Doria; Koshenov, Zhanat; Akishev, Zhiger; Maksimenko, Andrei; Bissenbaev, Amangeldy K; Matkarimov, Bakhyt T; Saparbaev, Murat; Ishchenko, Alexander A; Moréra, Solange

    2016-01-01

    Oxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, an AP endonuclease cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in the NIR pathway, the same AP endonuclease incises DNA 5' to an oxidized base. The majority of characterized AP endonucleases possess classic BER activities, and approximately a half of them can also have a NIR activity. At present, the molecular mechanism underlying DNA substrate specificity of AP endonucleases remains unclear mainly due to the absence of a published structure of the enzyme in complex with a damaged base. To identify critical residues involved in the NIR function, we performed biochemical and structural characterization of Bacillus subtilis AP endonuclease ExoA and compared its crystal structure with the structures of other AP endonucleases: Escherichia coli exonuclease III (Xth), human APE1, and archaeal Mth212. We found conserved amino acid residues in the NIR-specific enzymes APE1, Mth212, and ExoA. Four of these positions were studied by means of point mutations in APE1: we applied substitution with the corresponding residue found in NIR-deficient E. coli Xth (Y128H, N174Q, G231S, and T268D). The APE1-T268D mutant showed a drastically decreased NIR activity and an inverted Mg(2+) dependence of the AP site cleavage activity, which is in line with the presence of an aspartic residue at the equivalent position among other known NIR-deficient AP endonucleases. Taken together, these data show that NIR is an evolutionarily conserved function in the Xth family of AP endonucleases.

  10. Packaging design criteria, transfer and disposal of 102-AP mixer pump

    SciTech Connect

    Carlstrom, R.F.

    1994-11-23

    A mixer pump installed in storage tank 241-AP-102 (102-AP) has failed. This pump is referred to as the 102-AP mixer pump (APMP). The APMP will be removed from 102-AP 1 and a new pump will be installed. The main purpose of the Packaging Design Criteria (PDC) is to establish criteria necessary to design and fabricate a shipping container for the transfer and storage of the APMP from 102-AP. The PDC will be used as a guide to develop a Safety Evaluation for Packaging (SEP).

  11. Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes.

    PubMed

    Tolvanen, Tuomas A; Dash, Surjya Narayan; Polianskyte-Prause, Zydrune; Dumont, Vincent; Lehtonen, Sanna

    2015-12-15

    The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin-dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes.

  12. Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

    SciTech Connect

    Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa; San Filippo, Joseph San; Wiese, Claudia; Tsai, Miaw-Sheue; Begovic, Sead; Schild, David; Jasin, Maria; Keeney, Scott; Sung, Patrick

    2010-11-05

    Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partner and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.

  13. Purification of recombinant nacre-associated mineralization protein AP7 fused with maltose-binding protein.

    PubMed

    Huang, Yu-Chieh; Chang, Hsun-Hui; Mou, Yun; Chi, Peter; Chan, Jerry Chun Chung; Luo, Shih-Chi

    2014-08-01

    Formation of biominerals often involves specific proteins that modulate the process of matrix assembly, nucleation, and crystal growth. AP7 is an aragonite-associated protein of 7 kDa and is intrinsically disordered. The structural disorder of AP7 makes it very difficult to express in Escherchiacoli. In this work, we report the first successful expression and purification of recombinant AP7 using the maltose-binding protein (MBP) fusion approach. We obtain a high-yield production of recombinant MBP-AP7 protein inE. coli (∼60 mg/L). We also establish an efficient protocol to remove the MBP fusion protein by Factor Xa, followed by purification using size-exclusion chromatography. Characterization of the recombinant AP7 protein has been carried out using MALDI-TOF, peptide mass fingerprinting, and circular dichroism (CD). The mass data confirm that the purified recombinant protein is AP7. The CD data suggest that the recombinant AP7 protein exists as partially disordered structure at neutral pH. The calcium carbonate precipitation assay shows that both MBP-AP7 and AP7 exhibit morphological modification on calcite crystallites. The co-precipitation of MBP-tagged AP7 derivatives and calcium carbonate generate different types of AP7 composite calcite and vaterite crystals. This system should be helpful to establish a model for understanding the structure/function relationship between the protein and inorganic mineral interaction.

  14. The interaction between the adaptor protein APS and Enigma is involved in actin organisation.

    PubMed

    Barrès, Romain; Gonzalez, Teresa; Le Marchand-Brustel, Yannick; Tanti, Jean-François

    2005-08-15

    APS (adaptor protein with PH and SH2 domains) is an adaptor protein phosphorylated by several tyrosine kinase receptors including the insulin receptor. To identify novel binding partners of APS, we performed yeast two-hybrid screening. We identified Enigma, a PDZ and LIM domain-containing protein that was previously shown to be associated with the actin cytoskeleton. In HEK 293 cells, Enigma interacted specifically with APS, but not with the APS-related protein SH2-B. This interaction required the NPTY motif of APS and the LIM domains of Enigma. In NIH-3T3 cells that express the insulin receptor, Enigma and APS were partially co-localised with F-actin in small ruffling structures. Insulin increased the complex formation between APS and Enigma and their co-localisation in large F-actin containing ruffles. While in NIH-3T3 and HeLa cells the co-expression of both Enigma and APS did not modify the actin cytoskeleton organisation, expression of Enigma alone led to the formation of F-actin clusters. Similar alteration in actin cytoskeleton organisation was observed in cells expressing both Enigma and APS with a mutation in the NPTY motif. These results identify Enigma as a novel APS-binding protein and suggest that the APS/Enigma complex plays a critical role in actin cytoskeleton organisation.

  15. Ectopic expression of AP-2α transcription factor suppresses glioma progression.

    PubMed

    Su, Wenjing; Xia, Juan; Chen, Xueqin; Xu, Miao; Nie, Ling; Chen, Ni; Gong, Jing; Li, Xinglan; Zhou, Qiao

    2014-01-01

    The transcriptional factor AP-2α is a tumor suppressor gene and is downregulated in various neoplasms including glioma. Although the level of AP-2α is negatively associated with the grade of human glioma, the specific functions of AP-2α in glioma are still unknown. In this study, we experimentally showed that artificial overexpression of AP-2α in glioma T98G and U251 cells significantly downregulated the mRNA levels of Bcl-xl, Bcl-2, c-IAP2 and survivin, together with upregulation of the Hrk mRNA levels. Reintroduction of AP-2α also induced downregulation of the protein levels of survivin and VEGF in glioma cells. In biological assays with T98G and U251 cells, AP-2α reduced tumor cell growth, increased cell death, attenuated cell migration and endothelial tube formation. The AP-2α transcription factor may play an important role in suppressing glioma progression.

  16. Developing a Dedicated GISAXS Beamline at the APS

    NASA Astrophysics Data System (ADS)

    Li, Xuefa; Narayanan, Suresh; Sprung, Michael; Sandy, Alec; Lee, Dong Ryeol; Wang, Jin

    2007-01-01

    As an increasingly important structural-characterization technique, grazing-incidence small-angle scattering (GISAXS) finds vast applications in nanostructures and nanocomposites at surfaces and interfaces for in situ and real-time studies because of its probing q-range (10-3 - 1 nm-1) and temporal resolution (10-3 - 1 s). At the Advanced Photon Source (APS), GISAXS techniques under thin-film waveguide-based resonance conditions were developed to study the diffusion phenomena in nanoparticle/polymer nanocomposites. Also, the kinematics of nanoparticle crystal formation at air/liquid interfaces has been obtained by the similar method in real time during the liquid droplet evaporation. To meet the strong demand from the nanoscience community, a dedicated GISAXS beamline has been designed and constructed as a part of the 8-ID-E beamline at the APS. This dedicated GISAXS setup was developed based on a 4-circle diffractometer so that precise reflectivity of the sample can be measured to complement the GISAXS analysis under the dynamical refection conditions.

  17. Luteolin, a flavonoid, inhibits AP-1 activation by basophils

    SciTech Connect

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio . E-mail: ttanak@imed3.med.osaka-u.ac.jp

    2006-02-03

    Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

  18. Designing an artificial pancreas architecture: the AP@home experience.

    PubMed

    Lanzola, Giordano; Toffanin, Chiara; Di Palma, Federico; Del Favero, Simone; Magni, Lalo; Bellazzi, Riccardo

    2015-12-01

    The latest achievements in sensor technologies for blood glucose level monitoring, pump miniaturization for insulin delivery, and the availability of portable computing devices are paving the way toward the artificial pancreas as a treatment for diabetes patients. This device encompasses a controller unit that oversees the administration of insulin micro-boluses and continuously drives the pump based on blood glucose readings acquired in real time. In order to foster the research on the artificial pancreas and prepare for its adoption as a therapy, the European Union in 2010 funded the AP@home project, following a series of efforts already ongoing in the USA. This paper, authored by members of the AP@home consortium, reports on the technical issues concerning the design and implementation of an architecture supporting the exploitation of an artificial pancreas platform. First a PC-based platform was developed by the authors to prove the effectiveness and reliability of the algorithms responsible for insulin administration. A mobile-based one was then adopted to improve the comfort for the patients. Both platforms were tested on real patients, and a description of the goals, the achievements, and the major shortcomings that emerged during those trials is also reported in the paper.

  19. The new AP Physics exams: Integrating qualitative and quantitative reasoning

    NASA Astrophysics Data System (ADS)

    Elby, Andrew

    2015-04-01

    When physics instructors and education researchers emphasize the importance of integrating qualitative and quantitative reasoning in problem solving, they usually mean using those types of reasoning serially and separately: first students should analyze the physical situation qualitatively/conceptually to figure out the relevant equations, then they should process those equations quantitatively to generate a solution, and finally they should use qualitative reasoning to check that answer for plausibility (Heller, Keith, & Anderson, 1992). The new AP Physics 1 and 2 exams will, of course, reward this approach to problem solving. But one kind of free response question will demand and reward a further integration of qualitative and quantitative reasoning, namely mathematical modeling and sense-making--inventing new equations to capture a physical situation and focusing on proportionalities, inverse proportionalities, and other functional relations to infer what the equation ``says'' about the physical world. In this talk, I discuss examples of these qualitative-quantitative translation questions, highlighting how they differ from both standard quantitative and standard qualitative questions. I then discuss the kinds of modeling activities that can help AP and college students develop these skills and habits of mind.

  20. Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter.

    PubMed

    Benkoussa, Madjid; Brand, Céline; Delmotte, Marie-Hélène; Formstecher, Pierre; Lefebvre, Philippe

    2002-07-01

    Retinoids exhibit antineoplastic activities that may be linked to retinoid receptor-mediated transrepression of activating protein 1 (AP1), a heterodimeric transcription factor composed of fos- and jun-related proteins. Here we show that transcriptional activation of an AP1-regulated gene through the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway (MAPK(ERK)) is characterized, in intact cells, by a switch from a fra2-junD dimer to a junD-fosB dimer loading on its promoter and by simultaneous recruitment of ERKs, CREB-binding protein (CBP), and RNA polymerase II. All-trans-retinoic acid (atRA) receptor (RAR) was tethered constitutively to the AP1 promoter. AP1 transrepression by retinoic acid was concomitant to glycogen synthase kinase 3 activation, negative regulation of junD hyperphosphorylation, and to decreased RNA polymerase II recruitment. Under these conditions, fra1 loading to the AP1 response element was strongly increased. Importantly, CBP and ERKs were excluded from the promoter in the presence of atRA. AP1 transrepression by retinoids was RAR and ligand dependent, but none of the functions required for RAR-mediated transactivation was necessary for AP1 transrepression. These results indicate that transrepressive effects of retinoids are mediated through a mechanism unrelated to transcriptional activation, involving the RAR-dependent control of transcription factors and cofactor assembly on AP1-regulated promoters.

  1. Retinoic Acid Receptors Inhibit AP1 Activation by Regulating Extracellular Signal-Regulated Kinase and CBP Recruitment to an AP1-Responsive Promoter

    PubMed Central

    Benkoussa, Madjid; Brand, Céline; Delmotte, Marie-Hélène; Formstecher, Pierre; Lefebvre, Philippe

    2002-01-01

    Retinoids exhibit antineoplastic activities that may be linked to retinoid receptor-mediated transrepression of activating protein 1 (AP1), a heterodimeric transcription factor composed of fos- and jun-related proteins. Here we show that transcriptional activation of an AP1-regulated gene through the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway (MAPKERK) is characterized, in intact cells, by a switch from a fra2-junD dimer to a junD-fosB dimer loading on its promoter and by simultaneous recruitment of ERKs, CREB-binding protein (CBP), and RNA polymerase II. All-trans-retinoic acid (atRA) receptor (RAR) was tethered constitutively to the AP1 promoter. AP1 transrepression by retinoic acid was concomitant to glycogen synthase kinase 3 activation, negative regulation of junD hyperphosphorylation, and to decreased RNA polymerase II recruitment. Under these conditions, fra1 loading to the AP1 response element was strongly increased. Importantly, CBP and ERKs were excluded from the promoter in the presence of atRA. AP1 transrepression by retinoids was RAR and ligand dependent, but none of the functions required for RAR-mediated transactivation was necessary for AP1 transrepression. These results indicate that transrepressive effects of retinoids are mediated through a mechanism unrelated to transcriptional activation, involving the RAR-dependent control of transcription factors and cofactor assembly on AP1-regulated promoters. PMID:12052862

  2. X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

    PubMed Central

    Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

    2011-01-01

    Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

  3. Incorporating Ninth-Grade PSAT/NMSQT® Scores into AP Potential™ Predictions for AP® European History and AP World History. Statistical Report 2014-1

    ERIC Educational Resources Information Center

    Zhang, Xiuyuan; Patel, Priyank; Ewing, Maureen

    2015-01-01

    Historically, AP Potential™ correlations and expectancy tables have been based on 10th-and 11th-grade PSAT/NMSQT® examinees and 11th-and 12th-grade AP® examinees for all subjects (Zhang, Patel, & Ewing,2014; Ewing, Camara, & Millsap, 2006; Camara & Millsap, 1998). However, a large number of students take AP European History and AP…

  4. Identification of Cargo for Adaptor Protein (AP) Complexes 3 and 4 by Sucrose Gradient Profiling.

    PubMed

    Pertl-Obermeyer, Heidi; Wu, Xu Na; Schrodt, Jens; Müdsam, Christina; Obermeyer, Gerhard; Schulze, Waltraud X

    2016-09-01

    Intracellular vesicle trafficking is a fundamental process in eukaryotic cells. It enables cellular polarity and exchange of proteins between subcellular compartments such as the plasma membrane or the vacuole. Adaptor protein complexes participate in the vesicle formation by specific selection of the transported cargo. We investigated the role of the adaptor protein complex 3 (AP-3) and adaptor protein complex 4 (AP-4) in this selection process by screening for AP-3 and AP-4 dependent cargo proteins. Specific cargo proteins are expected to be mis-targeted in knock-out mutants of adaptor protein complex components. Thus, we screened for altered distribution profiles across a density gradient of membrane proteins in wild type versus ap-3β and ap-4β knock-out mutants. In ap-3β mutants, especially proteins with transport functions, such as aquaporins and plasma membrane ATPase, as well as vesicle trafficking proteins showed differential protein distribution profiles across the density gradient. In the ap-4β mutant aquaporins but also proteins from lipid metabolism were differentially distributed. These proteins also showed differential phosphorylation patterns in ap-3β and ap-4β compared with wild type. Other proteins, such as receptor kinases were depleted from the AP-3 mutant membrane system, possibly because of degradation after mis-targeting. In AP-4 mutants, membrane fractions were depleted for cytochrome P450 proteins, cell wall proteins and receptor kinases. Analysis of water transport capacity in wild type and mutant mesophyll cells confirmed aquaporins as cargo proteins of AP-3 and AP-4. The combination of organelle density gradients with proteome analysis turned out as a suitable experimental strategy for large-scale analyses of protein trafficking.

  5. Autonomous star sensor ASTRO APS: flight experience on Alphasat

    NASA Astrophysics Data System (ADS)

    Schmidt, U.; Fiksel, T.; Kwiatkowski, A.; Steinbach, I.; Pradarutti, B.; Michel, K.; Benzi, E.

    2015-06-01

    Jena-Optronik GmbH, located in Jena/Germany, has profound experience in designing and manufacturing star trackers since the early 80s. Today the company has a worldwide leading position in supplying geo-stationary and Earth observation satellites with robust and reliable star tracker systems. In the first decade of the new century Jena-Optronik received a development contract (17317/2003/F/WE) from the European Space Agency to establish the technologically challenging elements for which advanced star tracker technologies as CMOS Active Pixel Sensors were being introduced or were considered strategic. This activity was performed in the frame of the Alphabus large platform pre-development lead by ESA and the industrial Joint Project Team consisting of Astrium (now Airbus Defence and Space), Thales Alenia Space and CNES (Centre national d'études spatiales). The new autonomous star tracker, ASTRO APS (Active Pixel Sensor), extends the Jena-Optronik A stro-series CCD-based star tracker products taken the full benefit of the CMOS APS technology. ASTRO APS is a fully autonomous compact star tracker carrying either the space-qualified radiation hard STAR1000 or the HAS2 APS detectors. The star tracker is one of four Technology Demonstration Payloads (TDP6) carried by Alphasat as hosted payload in the frame of a successful Private Public Partnership between ESA and Inmarsat who owns and operates the satellite as part of its geo-stationary communication satellites fleet. TDP6 supports also directly TDP1, a Laser Communication Terminal, for fine pointing tasks. Alphasat was flawlessly brought in orbit at the end of July 2013 by a European Ariane 5 launcher. Only a few hours after launch the star tracker received its switch ON command and acquired nominally within 6 s the inertial 3-axes attitude. In the following days of the early in-orbit operations of Alphasat the TDP6 unit tracked reliably all the spacecraft maneuvers including the 0.1 and 0.2°/s spin stabilization for

  6. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities.

    PubMed

    Guo, Xiaoxiao; Ma, Chengbang; Du, Qiang; Wei, Ran; Wang, Lei; Zhou, Mei; Chen, Tianbao; Shaw, Chris

    2013-09-01

    Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160 μM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5 μM) and the yeast, Candida albicans (10 μM). Haemolytic activity of TsAP-1 was low (4% at 160 μM) and in contrast, that of TsAP-2 was considerably higher (18% at 20 μM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5 μM for S. aureus/C. albicans and 5 μM for E. coli but with an associated large increase in haemolytic activity (30% at 5 μM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E. coli lowering this from >320 μM to 5 μM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 μM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity.

  7. Expansion and Functional Divergence of AP2 Group Genes in Spermatophytes Determined by Molecular Evolution and Arabidopsis Mutant Analysis

    PubMed Central

    Wang, Pengkai; Cheng, Tielong; Lu, Mengzhu; Liu, Guangxin; Li, Meiping; Shi, Jisen; Lu, Ye; Laux, Thomas; Chen, Jinhui

    2016-01-01

    The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA-binding proteins called AP2/EREBP. The AP2 gene is functional and necessary for flower development, stem cell maintenance, and seed development, whereas the other members of AP2 group redundantly affect flowering time. Here we study the phylogeny of AP2 group genes in spermatophytes. Spermatophyte AP2 group genes can be classified into AP2 and TOE types, six clades, and we found that the AP2 group homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent, which indicates the AP2 type gene are more ancient and TOE type was split out of AP2 type and losing the major function. In Brassicaceae, the expansion of AP2 and TOE type lead to the gene number of AP2 group were up to six. Purifying selection appears to have been the primary driving force of spermatophyte AP2 group evolution, although positive selection occurred in the AP2 clade. The transition from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene function and the same situation was found in AtTOE2. Combining this evolutionary analysis and published research, the results suggest that typical AP2 group genes may first appear in gymnosperms and diverged in angiosperms, following expansion of group members and functional differentiation. In angiosperms, AP2 genes (AP2 clade) inherited key functions from ancestors and other genes of AP2 group lost most function but just remained flowering time controlling in gene formation. In this study, the phylogenies of AP2 group genes in spermatophytes was analyzed, which supported the evidence for the research of gene functional evolution of AP2 group. PMID:27703459

  8. RAD51AP2, a novel vertebrate- and meiotic-specific protein, sharesa conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51

    SciTech Connect

    Kovalenko, Oleg V.; Wiese, Claudia; Schild, David

    2006-07-25

    Many interacting proteins regulate and/or assist the activities of RAD51, a recombinase which plays a critical role in both DNA repair and meiotic recombination. Yeast two-hybrid screening of a human testis cDNA library revealed a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly with RAD51. A full-length cDNA clone predicts a novel vertebrate specific protein of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is ubiquitously expressed. Analyses using truncations and point mutations in both RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding motif, but this homologous region plays only an accessory role to the adjacent main RAD51-interacting region, which has been narrowed here to 40 amino acids. A novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a C-terminal motif also present in RAD51AP1.

  9. Duplication of AP1 within the Spinacia oleracea L. AP1/FUL clade is followed by rapid amino acid and regulatory evolution.

    PubMed

    Sather, D Noah; Golenberg, Edward M

    2009-02-01

    The AP1/FUL clade of MADS box genes have undergone multiple duplication events among angiosperm species. While initially identified as having floral meristem identity and floral organ identity function in Arabidopsis, the role of AP1 homologs does not appear to be universally conserved even among eudicots. In comparison, the role of FRUITFULL has not been extensively explored in non-model species. We report on the isolation of three AP1/FUL genes from cultivated spinach, Spinacia oleracea L. Two genes, designated SpAPETALA1-1 (SpAP1-1) and SpAPETALA1-2 (SpAP1-2), cluster as paralogous genes within the Caryophyllales AP1 clade. They are highly differentiated in the 3', carboxyl-end encoding region of the gene following the third amphipathic alpha-helix region, while still retaining some elements of a signature AP1 carboxyl motifs. In situ hybridization studies also demonstrate that the two paralogs have evolved different temporal and spatial expression patterns, and that neither gene is expressed in the developing sepal whorl, suggesting that the AP1 floral organ identity function is not conserved in spinach. The spinach FRUITFULL homolog, SpFRUITFULL (SpFUL), has retained the conserved motif and groups with Caryophyllales FRUITFULL homologs. SpFUL is expressed in leaf as well as in floral tissue, and shows strong expression late in flower development, particularly in the tapetal layer in males, and in the endothecium layer and stigma, in the females. The combined evidence of high rates of non-synonymous substitutions and differential expression patterns supports a scenario in which the AP1 homologs in the spinach AP1/FUL gene family have experienced rapid evolution following duplication.

  10. Expansion and stress responses of AP2/EREBP superfamily in Brachypodium distachyon.

    PubMed

    Chen, Lihong; Han, Jiapeng; Deng, Xiaomin; Tan, Shenglong; Li, Lili; Li, Lun; Zhou, Junfei; Peng, Hai; Yang, Guangxiao; He, Guangyuan; Zhang, Weixiong

    2016-02-12

    APETALA2/ethylene-responsive element binding protein (AP2/EREBP) transcription factors constitute one of the largest and most conserved gene families in plant, and play essential roles in growth, development and stress response. Except a few members, the AP2/EREBP family has not been characterized in Brachypodium distachyon, a model plant of Poaceae. We performed a genome-wide study of this family in B. distachyon by phylogenetic analyses, transactivation assays and transcript profiling. A total of 149 AP2/EREBP genes were identified and divided into four subfamilies, i.e., ERF (ethylene responsive factor), DREB (dehydration responsive element binding gene), RAV (related to ABI3/VP) and AP2. Tandem duplication was a major force in expanding B. distachyon AP2/EREBP (BdAP2/EREBP) family. Despite a significant expansion, genomic organizations of BdAP2/EREBPs were monotonous as the majority of them, except those of AP2 subfamily, had no intron. An analysis of transcription activities of several closely related and duplicated BdDREB genes showed their functional divergence and redundancy in evolution. The expression of BdAP2/EREBPs in different tissues and the expression of DREB/ERF subfamilies in B. distachyon, wheat and rice under abiotic stresses were investigated by next-generation sequencing and microarray profiling. Our results are valuable for further function analysis of stress tolerant AP2/EREBP genes in B. distachyon.

  11. A High-speed Photometric Survey of AP Stars

    NASA Astrophysics Data System (ADS)

    Kurtanidze, O. M.; Nikolashvili, M. G.

    We have undertook a long-term programme of high-speed photometric observations about two hundred Normal and Peculiar A-type stars with 125cm RC telescope equipped by Two-Star Photometer. It enables to chop as frequently as need between objects, sky and dark due to effects of sky transparency and background variations are removed and scintillation noise spectra are obtained. An attempt was made to include representative number of each spectral subtypes. The selected objects lie in the range of 8-10 magnitudes in the Jonhson wide-band B filter. At first stage it is planned to carry out a pilot survey with duration of 6-8 hours divided between two or three observing sessions. The objects with noticable oscillations will be studied photometrically as well as spectroscopically in detail. During the preliminary observations one rapidly-oscillating Ap star HD231427 was revealed which should be considered as tentative.

  12. A high-speed photometric survey of AP stars

    NASA Astrophysics Data System (ADS)

    Nikolashvili, M. G.; Kurtanidze, O. M.

    We have undertook a long-term programme of high-speed photometric observations about two hundred Normal and Peculiar A-type stars with 125cm RC telescope equipped by Two-Star Photometer. It enables to chop as frequently as need between objects, sky and dark due to effects of sky transparency and background variations are removed and scintillation noise spectra are obtained. An attempt was made to include representative number of each spectral subtypes. The selected objects lie in the range of 8-10 magnitudes in the Jonhson wide-band B filter. At first stage it is planned to carry out a pilot survey with duration of 6-8 hours divided between two or three observing sessions. The objects with noticable oscillations will be studied photometrically as well as spectroscopically in detail. During the preliminary observations one rapidly-oscillating Ap star HD231427 was revealed which should be considered as tentative.

  13. Thermal analysis of the crotch absorber in APS

    NASA Astrophysics Data System (ADS)

    Sheng, I. C. A.; Howell, Joseph W.

    1993-02-01

    A crotch absorber design for use in the Advanced Photon Source (APS) has been proposed and analyzed. The absorber is placed downstream of sectors S2 and S4 in the curved storage ring chamber and is subjected to a peak power of 120 W/mm2 per 100 mA synchrotron radiation. A beryllium ring is brazed on the GlidCop cooling cylinder in order to diffuse the concentrated bending magnet heating. One concentric water channel and two annular return water channels are arranged in the GlidCop cylinder to enhance the cooling. A Bodner-Partom thermoviscoplastic constitutive equation and a modified Manson-Coffin fatigue relation are proposed to simulate the cyclic thermal loading, as well as to predict the thermal fatigue life of the crotch absorber. Results of temperature and stress using finite element computations are displayed and a series of e-beam welder tests and microstructure measurements are reported.

  14. Thermal analysis of the crotch absorber in APS

    SciTech Connect

    Sheng, I.C.; Howell, J.

    1992-01-01

    A crotch absorber design for use in the Advanced Photon source (APS) has been proposed and analyzed. the absorber is placed downstream of sectors S2 and S4 in the curved storage ring chamber and will be subjected to a peak power of 120 W/mm{sup 2} per 100mA synchrotron radiation. A beryllium ring is brazed on the GlidCop cooling cylinder in order to diffuse the concentrated bending magnet heating. One concentric water channel and two annular return water channels are arranged in the GlidCop cylinder to enhance the cooling. A Bodner-Partom thermoviscoplastic constitutive equation and a modified Manson-Coffin fatigue relation are proposed to simulate the cyclic thermal loading, as well as to predict the thermal fatigue life of the crotch absorber. Results of temperature and stress using finite element computations are displayed and series of e-beam welder tests and microstructure measurements are reported.

  15. Thermal analysis of the crotch absorber in APS

    SciTech Connect

    Sheng, I.C.; Howell, J.

    1992-10-01

    A crotch absorber design for use in the Advanced Photon source (APS) has been proposed and analyzed. the absorber is placed downstream of sectors S2 and S4 in the curved storage ring chamber and will be subjected to a peak power of 120 W/mm{sup 2} per 100mA synchrotron radiation. A beryllium ring is brazed on the GlidCop cooling cylinder in order to diffuse the concentrated bending magnet heating. One concentric water channel and two annular return water channels are arranged in the GlidCop cylinder to enhance the cooling. A Bodner-Partom thermoviscoplastic constitutive equation and a modified Manson-Coffin fatigue relation are proposed to simulate the cyclic thermal loading, as well as to predict the thermal fatigue life of the crotch absorber. Results of temperature and stress using finite element computations are displayed and series of e-beam welder tests and microstructure measurements are reported.

  16. Aerosol Polarimetry Sensor (APS): Design Summary, Performance and Potential Modifications

    NASA Technical Reports Server (NTRS)

    Cairns, Brian

    2014-01-01

    APS is a mature design that has already been built and has a TRL of 7. Algorithmic and retrieval capabilities continue to improve and make better and more sophisticated used of the data. Adjoint solutions, both in one dimensional and three dimensional are computationally efficient and should be the preferred implementation for the calculation of Jacobians (one dimensional), or cost-function gradients (three dimensional). Adjoint solutions necessarily provide resolution of internal fields and simplify incorporation of active measurements in retrievals, which will be necessary for a future ACE mission. Its best to test these capabilities when you know the answer: OSSEs that are well constrained observationally provide the best place to test future multi-instrument platform capabilities and ensure capabilities will meet scientific needs.

  17. The chemical abundances of the Ap star HD94660

    SciTech Connect

    Giarrusso, M.

    2014-05-09

    In this work I present the determination of chemical abundances of the Ap star HD94660, a possible rapid oscillating star. As all the magnetic chemically peculiar objects, it presents CNO underabundance and overabundance of iron peak elements of ∼100 times and of rare earths up to 4 dex with respect to the Sun. The determination was based on the conversion of the observed equivalent widths into abundances simultaneously to the determination of effective temperature and gravity. Since the Balmer lines of early type stars are very sensitive to the surface gravity while the flux distribution is sensitive to the effective temperature, I have adopted an iterative procedure to match the H{sub α} line profile and the observed UV-Vis-NIR magnitudes of HD94660 looking for a consistency between the metallicity of the atmosphere model and the derived abundances. From my spectroscopic analysis, this star belongs to the no-rapid oscillating class.

  18. Nomenclature and name assignment rules for the APS storage ring

    SciTech Connect

    Decker, G.

    1992-03-16

    Because the APS accelerators are moving into the fabrication/assembly/installation stage, it is important for consistent naming conventions to be used throughout the project. The intent of this note is to dictate the rules to be adhered to when naming devices in the storage ring. These rules are generic in nature, and shall be applied in principle to the other machines as well. It is essential that every component have a unique and, hopefully, easily recognizable name. Every ASD and XFD group, except for magnets, must interface with the control system. For this reason all device names were developed keeping in mind their actual function, such as controlling or monitoring some device in the ring. Even though magnets are not directly interfaced to the control system, their power supplies are; therefore, a magnet will have the same name as its associated power supply.

  19. Klystron modulator operation and upgrades for the APS linac

    SciTech Connect

    Russell, T.J.; Cours, A.

    1995-07-01

    The Advanced Photon Source (APS) linac requires five 100-MW modulators to achieve its required energy. In-house construction of these modulators was under an extremely compressed time schedule and, while the original design was successful, it had a few shortcomings. The operation of the modulators was hindered by excessively sensitive controls and overheating during the hot summer months. The system underwent minor changes that resulted in major improvements. Additionally, improvements have been made to the high voltage circuits to improve the rise time of the output pulse shape. reduce the initial ringing of the pulse, and enhance the reliability of the system. This paper will outline the changes and explain the results of the improvements.

  20. The APS intranet as a man-machine interface.

    SciTech Connect

    Ciarlette, D.; Gerig, R.; McDowell, W.

    1997-12-02

    The Advanced Photon Source at Argonne National Laboratory has implemented a number of methods for people to interact with the accelerator systems. The accelerator operators use Sun workstations running MEDM and WCL to interface interactively with the accelerator, however, many people need to view information rather than interact with the machine. One of the most common interfaces for viewing information at the Advanced Photon Source is the World Wide Web. Information such as operations logbook entries, machine status updates, and displays of archived and current data are easily available to APS personnel. This interface between people and the accelerator has proven to be quite useful. Because the Intranet is operating-system independent and inherently unidirectional, ensuring the prevention of unauthorized or accidental control of the accelerators is straightforward.

  1. Fabrication and Testing of Deflecting Cavities for APS

    SciTech Connect

    Mammosser, John; Wang, Haipeng; Rimmer, Robert; Jim, Henry; Katherine, Wilson; Dhakal, Pashupati; Ali, Nassiri; Jim, Kerby; Jeremiah, Holzbauer; Genfa, Wu; Joel, Fuerst; Yawei, Yang; Zenghai, Li

    2013-09-01

    Jefferson Lab (Newport News, Virginia) in collaboration with Argonne National Laboratory (Argonne, IL) has fabricated and tested four first article, 2.8 GHz, deflecting SRF cavities, for Argonne's Short-Pulse X-ray (SPX) project. These cavities are unique in many ways including the fabrication techniques in which the cavity cell and waveguides were fabricated. These cavity subcomponents were milled from bulk large grain niobium ingot material directly from 3D CAD files. No forming of sub components was used with the exception of the beam-pipes. The challenging cavity and helium vessel design and fabrication results from the stringent RF performance requirements required by the project and operation in the APS ring. Production challenges and fabrication techniques as well as testing results will be discussed in this paper.

  2. Conceptualizing Ideal Circuit Elements in the AP Physics C Syllabus

    NASA Astrophysics Data System (ADS)

    Morse, Robert A.

    2005-11-01

    Does it ever bother you that emfs, resistors, and inductors add in series, but capacitors add in parallel? Does it bother your students? The AP Physics C syllabus for electricity and magnetism specifies the mathematical models students are expected to not merely memorize but to understand. Over time, my students' questions have made me rethink my conceptual and mathematical understanding of this material to help them efficiently develop reasonable conceptual and mathematical models of E&M. In this paper I describe aspects of this pedagogical rethinking related to four ideal circuit elements. I specify the end state of understanding that I want students to develop, but do not attempt to detail the pedagogical path to that understanding.

  3. Dropping of mixing pump in Tank 102-AP

    SciTech Connect

    Jimenez, R.F.

    1995-06-02

    The purpose of this study is to examine dropping of the mixing pump in Tank 102-AP during its removal poses the risk of causing a leak in the tank bottom with attendant potential for public exposure from the leak. The purpose of this investigation is to examine the potential for causing such a leak (i.e., estimated frequency of leak occurrence); to qualitatively estimate leak magnitude if its is a credible event; and, finally to compare the worker hazard, in the installation of an impact limiter (should it be required), to that which the public might incur if a leak is manifest in the tank bottom. The ultimate goal of the study is, of course, to assess the need for installation of an impact limiter.

  4. Global coupling and decoupling of the APS storage ring

    SciTech Connect

    Chae, Y.C.; Liu, J.; Teng, L.C.

    1993-07-01

    This paper describes a study of controlling the coupling between the horizontal and the vertical betatron oscillations in the 7-GeV Advanced Photon Source (APS) storage ring. First, we investigate the strengthening of coupling using two families of skew quadrupoles. Twenty skew quadrupoles are arranged in the 40 sectors of the storage ring and powered in such a way so as to generate both quadrature components of the required 21st harmonic. The numerical results from tracking a single particle are presented for the various configurations of skew quadrupoles. Second, we describe the global decoupling procedure to minimize the unwanted coupling effects. These are mainly due to the random roll errors of normal quadruples. It is shown that even with the rather large rms roll error of 2 mrad, the coupling effects can be compensated for with 20 skew quadrupoles each having maximum strength one order of magnitude lower than the typical normal quadrupole strength.

  5. Improved temperature regulation of APS linac RF components.

    SciTech Connect

    Dortwegt, R.

    1998-09-21

    The temperature of the APS S-Band linac's high-power rf components is regulated by water from individual closed-loop deionized (DI) water systems. The rf components are all made of oxygen-free high-conductivity copper and respond quickly to temperature changes. The SLED cavities are especially temperature-sensitive and cause beam energy instabilities when the temperature is not well regulated. Temperature regulation better than {+-} 0.1 F is required to achieve good energy stability. Improvements in the closed-loop water systems have enabled them to achieve a regulation of {+-} 0.05 F over long periods. Regulation philosophy and equipment are discussed and numerical results are presented.

  6. Apurinic/apyrimidinic (AP) site recognition by the 5'-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1).

    PubMed

    Khodyreva, S N; Prasad, R; Ilina, E S; Sukhanova, M V; Kutuzov, M M; Liu, Y; Hou, E W; Wilson, S H; Lavrik, O I

    2010-12-21

    The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction of the PARP-1/AP site DNA complex resulted in covalent cross-linking of PARP-1 to DNA; the identity of cross-linked PARP-1 was confirmed by mass spectrometry. Using purified human PARP-1, the specificity of PARP-1 binding to AP site-containing DNA was confirmed in competition binding experiments. PARP-1 was only weakly activated to conduct poly(ADP-ribose) synthesis upon binding to AP site-containing DNA, but was strongly activated for poly(ADP-ribose) synthesis upon strand incision by AP endonuclease 1 (APE1). By virtue of its binding to AP sites, PARP-1 could be poised for its role in base excision repair, pending DNA strand incision by APE1 or the 5'-dRP/AP lyase activity in PARP-1.

  7. Basolateral sorting of the Mg²⁺ transporter CNNM4 requires interaction with AP-1A and AP-1B.

    PubMed

    Hirata, Yusuke; Funato, Yosuke; Miki, Hiroaki

    2014-12-12

    Ancient conserved domain protein/cyclin M (CNNM) 4 is an evolutionarily conserved Mg(2+) transporter that localizes at the basolateral membrane of the intestinal epithelia. Here, we show the complementary importance of clathrin adaptor protein (AP) complexes AP-1A and AP-1B in basolateral sorting of CNNM4. We first confirmed the basolateral localization of both endogenous and ectopically expressed CNNM4 in Madin-Darby Canine Kidney cells, which form highly polarized epithelia in culture. Single knockdown of μ1B, a cargo-recognition subunit of AP-1B, did not affect basolateral localization, but simultaneous knockdown of the μ1A subunit of AP-1A abrogated localization. Mutational analyses showed the importance of three conserved dileucine motifs in CNNM4 for both basolateral sorting and interaction with μ1A and μ1B. These results imply that CNNM4 is sorted to the basolateral membrane by the complementary function of AP-1A and AP-1B.

  8. Interplay between TAp73 Protein and Selected Activator Protein-1 (AP-1) Family Members Promotes AP-1 Target Gene Activation and Cellular Growth.

    PubMed

    Subramanian, Deepa; Bunjobpol, Wilawan; Sabapathy, Kanaga

    2015-07-24

    Unlike p53, which is mutated at a high rate in human cancers, its homologue p73 is not mutated but is often overexpressed, suggesting a possible context-dependent role in growth promotion. Previously, we have shown that co-expression of TAp73 with the proto-oncogene c-Jun can augment cellular growth and potentiate transactivation of activator protein (AP)-1 target genes such as cyclin D1. Here, we provide further mechanistic insights into the cooperative activity between these two transcription factors. Our data show that TAp73-mediated AP-1 target gene transactivation relies on c-Jun dimerization and requires the canonical AP-1 sites on target gene promoters. Interestingly, only selected members of the Fos family of proteins such as c-Fos and Fra1 were found to cooperate with TAp73 in a c-Jun-dependent manner to transactivate AP-1 target promoters. Inducible expression of TAp73 led to the recruitment of these Fos family members to the AP-1 target promoters on which TAp73 was found to be bound near the AP-1 site. Consistent with the binding of TAp73 and AP-1 members on the target promoters in a c-Jun-dependent manner, TAp73 was observed to physically interact with c-Jun specifically at the chromatin via its carboxyl-terminal region. Furthermore, co-expression of c-Fos or Fra1 was able to cooperate with TAp73 in potentiating cellular growth, similarly to c-Jun. These data together suggest that TAp73 plays a vital role in activation of AP-1 target genes via direct binding to c-Jun at the target promoters, leading to enhanced loading of other AP-1 family members, thereby leading to cellular growth.

  9. Kinetic properties of ATP sulfurylase and APS kinase from Thiobacillus denitrificans.

    PubMed

    Gay, Sean C; Fribourgh, Jennifer L; Donohoue, Paul D; Segel, Irwin H; Fisher, Andrew J

    2009-09-01

    The Thiobacillus denitrificans genome contains two sequences corresponding to ATP sulfurylase (Tbd_0210 and Tbd_0874). Both genes were cloned and expressed protein characterized. The larger protein (Tbd_0210; 544 residues) possesses an N-terminal ATP sulfurylase domain and a C-terminal APS kinase domain and was therefore annotated as a bifunctional enzyme. But, the protein was not bifunctional because it lacked ATP sulfurylase activity. However, the enzyme did possess APS kinase activity and displayed substrate inhibition by APS. Truncated protein missing the N-terminal domain had <2% APS kinase activity suggesting the function of the inactive sulfurylase domain is to promote the oligomerization of the APS kinase domains. The smaller gene product (Tbd_0874; 402 residues) possessed strong ATP sulfurylase activity with kinetic properties that appear to be kinetically optimized for the direction of APS utilization and ATP+sulfate production, which is consistent with an enzyme that functions physiologically to produce inorganic sulfate.

  10. Expression of transcription factor AP-2α predicts survival in epithelial ovarian cancer

    PubMed Central

    Anttila, M A; Kellokoski, J K; Moisio, K I; Mitchell, P J; Saarikoski, S; Syrjänen, K; Kosma, V-M

    2000-01-01

    The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2α was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2α antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2α was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2α protein only in the cytoplasm. In carcinomas nuclear AP-2α expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2α varied according to the histological subtype and differentiation. AP-2α and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13–2.18, P = 0.007) the high cytoplasmic AP-2α expression favoured the overall survival. In contrast, the nuclear AP-2α expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13–3.83, P = 0.018). The shift in the expression pattern of AP-2α (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2α in ovarian cancer may be due to post-transcriptional regulation. © 2000 Cancer Research Campaign PMID:10864206

  11. Genome-wide analysis of the AP2/ERF superfamily in peach (Prunus persica).

    PubMed

    Zhang, C H; Shangguan, L F; Ma, R J; Sun, X; Tao, R; Guo, L; Korir, N K; Yu, M L

    2012-10-17

    We identified 131 AP2/ERF (APETALA2/ethylene-responsive factor) genes in material from peach using the gene sequences of AP2/ERF amino acids of Arabidopsis thaliana (Brassicaceae) as probes. Based on the number of AP2/ERF domains and individual gene characteristics, the AP2/ERF superfamily gene in peach can be classified broadly into three families, ERF (ethylene-responsive factor), RAV (related to ABI3/VP1), and AP2 (APETALA2), containing 104, 5, and 21 members, respectively, along with a solo gene (ppa005376m). The 104 genes in the ERF family were further divided into 11 groups based on the group classification made for Arabidopsis. The scaffold localizations of the AP2/ERF genes indicated that 129 AP2/ERF genes were all located on scaffolds 1 to 8, except for two genes, which were on scaffolds 17 and 10. Although the primary structure varied among AP2/ERF superfamily proteins, their tertiary structures were similar. Most ERF family genes have no introns, while members of the AP2 family have more introns than genes in the ERF and RAV families. All sequences of AP2 family genes were disrupted by introns into several segments of varying sizes. The expression of the AP2/ERF superfamily genes was highest in the mesocarp; it was far higher than in the other seven tissues that we examined, implying that AP2/ERF superfamily genes play an important role in fruit growth and development in the peach. These results will be useful for selecting candidate genes from specific subgroups for functional analysis.

  12. Dexcom G4AP: an advanced continuous glucose monitor for the artificial pancreas.

    PubMed

    Garcia, Arturo; Rack-Gomer, Anna Leigh; Bhavaraju, Naresh C; Hampapuram, Haripriyan; Kamath, Apurv; Peyser, Thomas; Facchinetti, Andrea; Zecchin, Chiara; Sparacino, Giovanni; Cobelli, Claudio

    2013-11-01

    Input from continuous glucose monitors (CGMs) is a critical component of artificial pancreas (AP) systems, but CGM performance issues continue to limit progress in AP research. While G4 PLATINUM has been integrated into AP systems around the world and used in many successful AP controller feasibility studies, this system was designed to address the needs of ambulatory CGM users as an adjunctive use system. Dexcom and the University of Padova have developed an advanced CGM, called G4AP, to specifically address the heightened performance requirements for future AP studies. The G4AP employs the same sensor and transmitter as the G4 PLATINUM but contains updated denoising and calibration algorithms for improved accuracy and reliability. These algorithms were applied to raw data from an existing G4 PLATINUM clinical study using a simulated prospective procedure. The results show that mean absolute relative difference (MARD) compared with venous plasma glucose was improved from 13.2% with the G4 PLATINUM to 11.7% with the G4AP. Accuracy improvements were seen over all days of sensor wear and across the plasma glucose range (40-400 mg/dl). The greatest improvements occurred in the low glucose range (40-80 mg/dl), in euglycemia (80-120 mg/dl), and on the first day of sensor use. The percentage of sensors with a MARD <15% increased from 69% to 80%. Metrics proposed by the AP research community for addressing specific AP requirements were also computed. The G4AP consistently exhibited improved sensor performance compared with the G4 PLATINUM. These improvements are expected to enable further advances in AP research.

  13. HPV16 E6 and E6AP differentially cooperate to stimulate or augment Wnt signaling

    SciTech Connect

    Sominsky, Sophia; Kuslansky, Yael; Shapiro, Beny; Jackman, Anna; Haupt, Ygal; Rosin-Arbesfeld, Rina; Sherman, Levana

    2014-11-15

    The present study investigated the roles of E6 and E6AP in the Wnt pathway. We showed that E6 levels are markedly reduced in cells in which Wnt signaling is activated. Coexpression of wild-type or mutant E6AP (C820A) in Wnt-activated cells stabilized E6 and enhanced Wnt/β-catenin/TCF transcription. Expression of E6AP alone in nonstimulated cells elevated β-catenin level, promoted its nuclear accumulation, and activated β-catenin/TCF transcription. A knockdown of E6AP lowered β-catenin levels. Coexpression with E6 intensified the activities of E6AP. Further experiments proved that E6AP/E6 stabilize β-catenin by protecting it from proteasomal degradation. This function was dependent on the catalytic activity of E6AP, the kinase activity of GSK3β and the susceptibility of β-catenin to GSK3β phosphorylation. Thus, this study identified E6AP as a novel regulator of the Wnt signaling pathway, capable of cooperating with E6 in stimulating or augmenting Wnt/β-catenin signaling, thereby possibly contributing to HPV carcinogenesis. - Highlights: • The roles of E6 and E6AP in the Wnt pathway were investigated. • E6AP stabilizes E6 and enhances E6 activity in augmentation of Wnt signaling. • E6AP cooperates with E6 to stabilize β-catenin and stimulate Wnt/β-catenin signaling. • E6AP and E6 act through different mechanisms to augment or stimulate Wnt signaling.

  14. Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

    PubMed

    Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

    2012-06-01

    DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site.

  15. APS-U Definitions of Signs and Conventions Related to Magnets

    SciTech Connect

    Doose, Charles; Jain, Animesh

    2014-08-21

    The APS-U is planned to be a 4th generation hard X-ray light source utilizing a multi-bend achromat (MBA) magnet lattice. The MBA lattice will be installed in the existing APS storage ring enclosure. The stored electron beam will circulate clockwise when viewed from above. The X-ray beamlines will for the most part exit at the same source points as the present APS. This document defines the signs and conventions related to the APS-U MBA magnets. Included in this document are: the local magnet coordinate system, definitions of mechanical and magnetic centers, definitions of multipole field errors, magnetic roll angle, and magnet polarities.

  16. Isolation, classification and transcription profiles of the AP2/ERF transcription factor superfamily in citrus.

    PubMed

    Xie, Xiu-lan; Shen, Shu-ling; Yin, Xue-ren; Xu, Qian; Sun, Chong-de; Grierson, Donald; Ferguson, Ian; Chen, Kun-song

    2014-07-01

    The AP2/ERF gene family encodes plant-specific transcription factors. In model plants, AP2/ERF genes have been shown to be expressed in response to developmental and environmental stimuli, and many function downstream of the ethylene, biotic, and abiotic stress signaling pathways. In citrus, ethylene is effective in regulation citrus fruit quality, such as degreening and aroma. However, information about the citrus AP2/ERF family is limited, and would enhance our understanding of fruit responses to environmental stress, fruit development and quality. CitAP2/ERF genes were isolated using the citrus genome database, and their expression patterns analyzed by real-time PCR using various orange organs and samples from a fruit developmental series. 126 sequences with homologies to AP2/ERF proteins were identified from the citrus genome, and, on the basis of their structure and sequence, assigned to the ERF family (102), AP2 family (18), RAV family (4) and Soloist (2). MEME motif analysis predicted the defining AP2/ERF domain and EAR repressor domains. Analysis of transcript accumulation in Citrus sinensis cv. 'Newhall' indicated that CitAP2/ERF genes show organ-specific and temporal expression, and provided a framework for understanding the transcriptional regulatory roles of AP2/ERF gene family members in citrus. Hierarchical cluster analysis and t tests identified regulators that potentially function during orange fruit growth and development.

  17. AP-2β is a transcriptional regulator for determination of digit length in tetrapods.

    PubMed

    Seki, Ryohei; Kitajima, Keiichi; Matsubara, Haruka; Suzuki, Takayuki; Saito, Daisuke; Yokoyama, Hitoshi; Tamura, Koji

    2015-11-01

    The species-specific morphology of digits in the tetrapod limb, including the length and number of metacarpal, metatarsal, and phalangeal bones, suggests that a common developmental mechanism for digit formation is modified in a species-specific manner. Here, we examined the function of the AP-2β transcription factor in regulating digit length in the chicken autopod. Mutations in the gene encoding AP-2β are associated with Char syndrome, a human autosomal dominant disorder. Char syndrome patients exhibit autopod skeletal defects, including loss of phalanges and shortened fingers, suggestive of a function for AP-2β in normal digit development. The ectopic expression of two different dominant-negative forms of chick AP-2β, equivalent to mutant forms associated with human Char syndrome, in the developing chick hindlimb bud resulted in defective digit formation, including reductions in the number and length of phalanges and metatarsals. A detailed analysis of the AP-2β expression pattern in the limb bud indicated a correlation between the pattern/duration of AP-2β expression in the limb mesenchyme and digit length in three amniote species, the chicken, mouse and gecko. In addition, we found that AP-2β expression was downstream of Fgf signals from the apical ectodermal ridge, which is crucial in digit morphogenesis, and that excessive AP-2β function resulted in dysregulated digit length. Taken together, these results suggest that AP-2β functions as a novel transcriptional regulator for digit morphogenesis.

  18. Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

    PubMed Central

    Williams, Michael J.; Goergen, Philip; Rajendran, Jayasimman; Zheleznyakova, Galina; Hägglund, Maria G.; Perland, Emelie; Bagchi, Sonchita; Kalogeropoulou, Argyro; Khan, Zaid; Fredriksson, Robert; Schiöth, Helgi B.

    2014-01-01

    In all animals managing the size of individual meals and frequency of feeding is crucial for metabolic homeostasis. In the current study we demonstrate that the noradrenalin analogue octopamine and the cholecystokinin (CCK) homologue Drosulfakinin (Dsk) function downstream of TfAP-2 and Tiwaz (Twz) to control the number of meals in adult flies. Loss of TfAP-2 or Twz in octopaminergic neurons increased the size of individual meals, while overexpression of TfAP-2 significantly decreased meal size and increased feeding frequency. Of note, our study reveals that TfAP-2 and Twz regulate octopamine signaling to initiate feeding; then octopamine, in a negative feedback loop, induces expression of Dsk to inhibit consummatory behavior. Intriguingly, we found that the mouse TfAP-2 and Twz homologues, AP-2β and Kctd15, co-localize in areas of the brain known to regulate feeding behavior and reward, and a proximity ligation assay (PLA) demonstrated that AP-2β and Kctd15 interact directly in a mouse hypothalamus-derived cell line. Finally, we show that in this mouse hypothalamic cell line AP-2β and Kctd15 directly interact with Ube2i, a mouse sumoylation enzyme, and that AP-2β may itself be sumoylated. Our study reveals how two obesity-linked homologues regulate metabolic homeostasis by modulating consummatory behavior. PMID:25187989

  19. Enhancing and Archiving the APS Catalog of the POSS I

    NASA Technical Reports Server (NTRS)

    Humphreys, Roberta M.

    2003-01-01

    We have worked on two different projects: 1) Archiving the APS Catalog of the POSS I for distribution to NASA's NED at IPAC, SIMBAD in France, and individual astronomers and 2) The automated morphological classification of galaxies. We have completed archiving the Catalog into easily readable binary files. The database together with the software to read it has been distributed on DVD's to the national and international data centers and to individual astronomers. The archived Catalog contains more than 89 million objects in 632 fields in the first epoch Palomar Observatory Sky Survey. Additional image parameters not available in the original on-line version are also included in the archived version. The archived Catalog is also available and can be queried at the APS web site (URL: http://aps.umn.edu) which has been improved with a much faster and more efficient querying system. The Catalog can be downloaded as binary datafiles with the source code for reading it. It is also being integrated into the SkyQuery system which includes the Sloan Digital Sky Survey, 2MASS, and the FIRST radio sky survey. We experimented with different classification algorithms to automate the morphological classification of galaxies. This is an especially difficult problem because there are not only a large number of attributes or parameters and measurement uncertainties, but also the added complication of human disagreement about the adopted types. To solve this problem we used 837 galaxy images from nine POSS I fields at the North Galactic Pole classified by two independent astronomers for which they agree on the morphological types. The initial goal was to separate the galaxies into the three broad classes relevant to issues of large scale structure and galaxy formation and evolution: early (ellipticals and lenticulars), spirals, and late (irregulars) with an accuracy or success rate that rivals the best astronomer classifiers. We also needed to identify a set of parameters derived

  20. APS Alternative Fuel (Hydrogen) Pilot Plant - Monitoring System Report

    SciTech Connect

    James Francfort; Dimitri Hochard

    2005-07-01

    The U.S. Department of Energy’s (DOE’s) Advanced Vehicle Testing Activity (AVTA), along with Electric Transportation Applications and Arizona Pubic Service (APS), is monitoring the operations of the APS Alternative Fuel (Hydrogen) Pilot Plant to determine the costs to produce hydrogen fuels (including 100% hydrogen as well as hydrogen and compressed natural gas blends) for use by fleets and other operators of advanced-technology vehicles. The hydrogen fuel cost data will be used as benchmark data by technology modelers as well as research and development programs. The Pilot Plant can produce up to 18 kilograms (kg) of hydrogen per day by electrolysis. It can store up to 155 kg of hydrogen at various pressures up to 6,000 psi. The dispenser island can fuel vehicles with 100% hydrogen at 5,000 psi and with blends of hydrogen and compressed natural gas at 3,600 psi. The monitoring system was designed to track hydrogen delivery to each of the three storage areas and to monitor the use of electricity on all major equipment in the Pilot Plant, including the fuel dispenser island. In addition, water used for the electrolysis process is monitored to allow calculation of the total cost of plant operations and plant efficiencies. The monitoring system at the Pilot Plant will include about 100 sensors when complete (50 are installed to date), allowing for analysis of component, subsystems, and plant-level costs. The monitoring software is mostly off-the-shelve, with a custom interface. The majority of the sensors input to the Programmable Automation Controller as 4- to 20-mA analog signals. The plant can be monitored over of the Internet, but the control functions are restricted to the control room equipment. Using the APS general service plan E32 electric rate of 2.105 cents per kWh, during a recent eight-month period when 1,200 kg of hydrogen was produced and the plant capacity factor was 26%, the electricity cost to produce one kg of hydrogen was $3.43. However, the

  1. Preface: 18th Aps-Sccm and 24th Airapt

    NASA Astrophysics Data System (ADS)

    Collins, Gilbert; Moore, David S.; Yoo, Choong-Shik; Buttler, William; Furlanetto, Michael; Evans, William

    2014-05-01

    The 18th Biennial International Conference of the APS Topical Group on Shock Compression of Condensed Matter in conjunction with the 24th Biennial International Conference of the International Association for the Advancement of High Pressure Science & Technology (AIRAPT) was held at the Westin Hotel in Seattle, Washington from 7-12 July, 2013. This is only the second time that these two organizations have held a Joint Conference — the first was 20 years previous (1993) in Colorado Springs, Colorado. Seattle was chosen for this joint conference because of its central location for the world-wide attendees as well as its metropolitan vibrancy. The scientific program consisted of 858 scheduled presentations organized into 23 topical areas and included contributed (537), invited (95), and plenary (6) lectures, as well as two poster sessions with 110 posters each. The scientific focus of the Joint Conference was on fundamental and applied research topics related to the static or dynamic compression of condensed matter. This multidisciplinary field of research encompasses areas of physics, chemistry, materials science, mechanics, geophysics and planetary physics, and applied mathematics. Experimental, computational and theoretical studies all play important roles. The organizers endeavored to intertwine static and dynamic experimental alongside computational and theoretical studies of similar materials in the organization of the sessions. This goal was aided by the addition of three special focus sessions on deep carbon budget, high energy density materials, and dynamic response of materials. 722 scientists and engineers from 25 countries registered at the conference, including 132 students from 12 countries. The attendee countries represented included: Argentina (2), Australia (2), Brazil (3), Canada (25), China (22), Czech Republic (2), France (35), Germany (19), India (6), Israel (21), Italy (10), Japan (49), Netherlands (1), Poland (1), Portugal (2), Russia (26

  2. Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

    PubMed

    Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

    2013-06-01

    In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed.

  3. Magnetic AP Stars in the Hertzsprung-Russell Diagram

    NASA Astrophysics Data System (ADS)

    Hubrig, S.; North, P.; Mathys, G.

    2000-08-01

    The evolutionary state of magnetic Ap stars is rediscussed using the recently released Hipparcos data. The distribution of the magnetic Ap stars of mass below 3 Msolar in the H-R diagram differs from that of the normal stars in the same temperature range at a high level of significance. Magnetic stars are concentrated toward the center of the main-sequence band. This is shown in two forms of the H-R diagram: one where logL is plotted against logTeff and a version more directly tied to the observed quantities, showing the astrometry-based luminosity (Arenou & Luri) against the (B2-G)0 index of Geneva photometry. In particular, it is found that magnetic fields appear only in stars that have already completed at least approximately 30% of their main-sequence lifetime. No clear picture emerges as to the possible evolution of the magnetic field across the main sequence. Hints of some (loose) relations between magnetic field strength and other stellar parameters are found: stars with shorter periods tend to have stronger fields, as do higher temperature and higher mass stars. A marginal trend of the magnetic flux to be lower in more slowly rotating stars may possibly be seen as suggesting a dynamo origin for the field. No correlation between the rotation period and the fraction of the main-sequence lifetime completed is observed, indicating that the slow rotation in these stars must already have been achieved before they became observably magnetic. Based on data from the ESA Hipparcos satellite and on observations collected at the European Southern Observatory (La Silla, Chile; ESO programs Nos. 43.7-004, 44.7-012, 49.7-030, 50.7-067, 51.7-041, 52.7-063, 53.7-028, 54.E-0416, and 55.E-0751), at the Observatoire de Haute-Provence (Saint-Michel l'Observatoire, France), at Kitt Peak National Observatory, and at the Canada-France-Hawaii Telescope.

  4. AP-1/σ1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and Is Coupled to AP-2 Endocytosis.

    PubMed

    Kratzke, Manuel; Candiello, Ermes; Schmidt, Bernhard; Jahn, Olaf; Schu, Peter

    2015-08-01

    Adaptor protein (AP)-1/σ1B(-/-) mice have reduced synaptic-vesicle (SV) recycling and increased endosomes. Mutant mice have impaired spatial memory, and σ1B-deficient humans have a severe mental retardation. In order to define these σ1B(-/-) 'bulk' endosomes and to determine their functions in SV recycling, we developed a protocol to separate them from the majority of the neuronal endosomes. The σ1B(-/-) 'bulk' endosomes proved to be classic early endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate (PI-3-P), which recruits proteins mediating protein sorting out of early endosomes into different routes. σ1B deficiency induced alterations in the endosomal proteome reveals two major functions: SV protein storage and sorting into endolysosomes. Alternative endosomal recycling pathways are not up-regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in σ1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated-vesicles (CCVs), indicating AP-1/σ1B-dependent sorting. Synapses contain also more AP-2 CCV, although it is expected that they contain less due to reduced SV recycling. Coat composition of these AP-2 CCVs is altered, and thus, they represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent protein kinase (CaMK)-IIα, -δ and casein kinase (CK)-IIα with the endosome/SV pool is altered, as well as 14-3-3η, indicating changes in specific signalling pathways regulating synaptic plasticity. The accumulation of early endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via early endosomes by the interdependent regulation of AP-2-mediated endocytosis and AP-1/σ1B-mediated SV reformation.

  5. Behavioral comparison of sucrose and l-2-amino-4-phosphonobutyrate (L-AP4) tastes in rats: does L-AP4 have a sweet taste?

    PubMed

    Eschle, B K; Eddy, M C; Spang, C H; Delay, E R

    2008-08-13

    Even though it is generally thought that umami stimuli such as monosodium glutamate (MSG) and sweet stimuli such as sucrose are detected by different taste receptors, these stimuli appear to share taste qualities when amiloride (a sodium channel blocker) is present to reduce the sodium taste. Single fiber recording studies of the facial and glossopharyngeal nerves have shown that encoding of L-2-amino-4-phosphonobutyrate (L-AP4), a potent mGluR4 agonist that elicits a taste quite similar to MSG, may occur in the same fibers that also encode sweet stimuli. This suggests that L-AP4 and sweet substances may activate common receptors or afferent signaling mechanisms. We report results of behavioral experiments that test this hypothesis. In the first study, rats conditioned to avoid sucrose or L-AP4 generalized the aversion to the opposite substance, indicating that both substances elicited similar tastes. However, two taste discrimination experiments showed that rats easily discriminated between sucrose and L-AP4 over a wide range of concentrations, even when the cue function of sodium associated with L-AP4 was reduced by amiloride and neutralized by adding equimolar concentrations of NaCl to sucrose. These data suggest that even though L-AP4 and sucrose elicit similar taste qualities, one or both substances also elicit other taste qualities not shared by the opposite substance. They also suggest that the taste-mGluR4 receptor and the signal pathway activated by L-AP4 are not the same as those activated by sucrose. These data, when combined with fiber recording data, suggest that there is convergence of L-AP4 and sucrose signals at some point early in the gustatory pathway.

  6. Radioactive air emissions notice of construction for installation and operation of a waste retrieval system and tanks 241-AP-102 and 241-AP-104 project

    SciTech Connect

    DEXTER, M.L.

    1999-11-15

    This document serves as a notice of construction (NOC) pursuant to the requirements of Washington Administrative Code (WAC) 246 247-060, and as a request for approval to modify pursuant to 40 Code of Federal Regulations (CFR) 61 07 for the installation and operation of one waste retrieval system in the 24 1 AP-102 Tank and one waste retrieval system in the 241 AP 104 Tank Pursuant to 40 CFR 61 09 (a)( 1) this application is also intended to provide anticipated initial start up notification Its is requested that EPA approval of this application will also constitute EPA acceptance of the initial start up notification Project W 211 Initial Tank Retrieval Systems (ITRS) is scoped to install a waste retrieval system in the following double-shell tanks 241-AP 102-AP 104 AN 102, AN 103, AN-104, AN 105, AY 102 AZ 102 and SY-102 between now and the year 2011. Because of the extended installation schedules and unknowns about specific activities/designs at each tank, it was decided to submit NOCs as that information became available This NOC covers the installation and operation of a waste retrieval system in tanks 241 AP-102 and 241 AP 104 Generally this includes removal of existing equipment installation of new equipment and construction of new ancillary equipment and buildings Tanks 241 AP 102 and 241 AP 104 will provide waste feed for immobilization into a low activity waste (LAW) product (i.e. glass logs) The total effective dose equivalent (TEDE) to the offsite maximally exposed individual (MEI) from the construction activities is 0 045 millirem per year The unabated TEDE to the offsite ME1 from operation of the mixer pumps is 0 042 millirem per year.

  7. AP-1/σ1A and AP-1/σ1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway

    PubMed Central

    Candiello, Ermes; Kratzke, Manuel; Wenzel, Dirk; Cassel, Dan; Schu, Peter

    2016-01-01

    The σ1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express σ1A and one of the σ1B and σ1C isoforms. Brain is the tissue with the highest σ1A and σ1B expression. σ1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/σ1A and AP-1/σ1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. σ1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/σ1A-ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5GTP-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/σ1A-ArfGAP1-Rabex-5 complexes is prevented by σ1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation. PMID:27411398

  8. AP-1/σ1A and AP-1/σ1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway.

    PubMed

    Candiello, Ermes; Kratzke, Manuel; Wenzel, Dirk; Cassel, Dan; Schu, Peter

    2016-07-14

    The σ1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express σ1A and one of the σ1B and σ1C isoforms. Brain is the tissue with the highest σ1A and σ1B expression. σ1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/σ1A and AP-1/σ1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. σ1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/σ1A-ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5(GTP)-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/σ1A-ArfGAP1-Rabex-5 complexes is prevented by σ1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation.

  9. Identification of the Hevea brasiliensis AP2/ERF superfamily by RNA sequencing

    PubMed Central

    2013-01-01

    Background Rubber tree (Hevea brasiliensis) laticifers are the source of natural rubber. Rubber production depends on endogenous and exogenous ethylene (ethephon). AP2/ERF transcription factors, and especially Ethylene-Response Factors, play a crucial role in plant development and response to biotic and abiotic stresses. This study set out to sequence transcript expressed in various tissues using next-generation sequencing and to identify AP2/ERF superfamily in the rubber tree. Results The 454 sequencing technique was used to produce five tissue-type transcript libraries (leaf, bark, latex, embryogenic tissues and root). Reads from all libraries were pooled and reassembled to improve mRNA lengths and produce a global library. One hundred and seventy-three AP2/ERF contigs were identified by in silico analysis based on the amino acid sequence of the conserved AP2 domain from the global library. The 142 contigs with the full AP2 domain were classified into three main families (20 AP2 members, 115 ERF members divided into 11 groups, and 4 RAV members) and 3 soloist members. Fifty-nine AP2/ERF transcripts were found in latex. Alongside the microRNA172 already described in plants, eleven additional microRNAs were predicted to inhibit Hevea AP2/ERF transcripts. Conclusions Hevea has a similar number of AP2/ERF genes to that of other dicot species. We adapted the alignment and classification methods to data from next-generation sequencing techniques to provide reliable information. We observed several specific features for the ERF family. Three HbSoloist members form a group in Hevea. Several AP2/ERF genes highly expressed in latex suggest they have a specific function in Hevea. The analysis of AP2/ERF transcripts in Hevea presented here provides the basis for studying the molecular regulation of latex production in response to abiotic stresses and latex cell differentiation. PMID:23324139

  10. AP-2α-dependent regulation of Bcl-2/Bax expression affects apoptosis in the trophoblast.

    PubMed

    Zhang, Ling; Jia, Liting; Cui, Shihong; Shi, Ying; Chang, Aimin; Wang, Peng; Zhang, Zhan

    2012-12-01

    Enhanced apoptosis of the cytotrophoblast in early pregnancy is associated with a high risk of preeclampsia. We and others have previously reported that the transcriptional factor, activator protein AP-2α, suppressed trophoblast migration and invasion. However, it is not clear whether AP-2α affects apoptosis in trophoblast cells and whether it regulates expression of apoptosis-related factors Bcl-2 and Bax. We analyzed the expression of AP-2α, Bcl-2 and Bax in placental tissues in severe preeclamptic pregnancies and normotensive pregnancies using immunohistochemistry and real time-PCR. Further, apoptosis was assessed by flow cytometric analysis in the human trophoblastic cell line, BeWo cells, in which AP-2α expression was transiently overexpressed or down-regulated by siRNA. There was significantly higher expression of AP-2α and Bax, but lower expression of Bcl-2 in severe preeclampsia placentas as compared to the control placentas. Overexpression of AP-2α in BeWo cells led to an increased rate of apoptosis, whereas apoptosis was decreased when AP-2α expression was reduced. Furthermore, overexpression of AP-2α increased Bax expression and decreased Bcl-2 expression, whereas down-regulation of AP-2α expression resulted in a decrease in Bax expression and an increase in Bcl-2 expression. AP-2α regulates expression of Bcl-2 and Bax and apoptosis in BeWo cells. These results suggest that AP-2α-mediated regulation of Bcl-2 and Bax regulation influences apoptosis which in turn leads to the pathogenesis of preeclampsia.

  11. Measurements of the electron cloud in the APS storage ring.

    SciTech Connect

    Harkey, K. C.

    1999-04-16

    Synchrotron radiation interacting with the vacuum chamber walls in a storage ring produce photoelectrons that can be accelerated by the beam, acquiring sufficient energy to produce secondary electrons in collisions with the walls. If the secondary-electron yield (SEY) coefficient of the wall material is greater than one, as is the case with the aluminum chambers in the Advanced Photon Source (APS) storage ring, a runaway condition can develop. As the electron cloud builds up along a train of stored positron or electron bunches, the possibility exists that a transverse perturbation of the head bunch will be communicated to trailing bunches due to interaction with the cloud. In order to characterize the electron cloud, a special vacuum chamber was built and inserted into the ring. The chamber contains 10 rudimentary electron-energy analyzers, as well as three targets coated with different materials. Measurements show that the intensity and electron energy distribution are highly dependent on the temporal spacing between adjacent bunches and the amount of current contained in each bunch. Furthermore, measurements using the different targets are consistent with what would be expected based on the SEY of the coatings. Data for both positron and electron beams are presented.

  12. Trim69 regulates zebrafish brain development by ap-1 pathway

    PubMed Central

    Han, Ruiqin; Wang, Renxian; Zhao, Qing; Han, Yongqing; Zong, Shudong; Miao, Shiying; Song, Wei; Wang, Linfang

    2016-01-01

    Proteins belonging to the TRIM family have been implicated in a variety of cellular processes such as apoptosis, differentiation, neurogenesis, muscular physiology and innate immune responses. Trim69, previously identified as a novel gene cloned from a human testis cDNA library, has a homologous gene in zebrafish and this study focused on investigating the function of trim69 in zebrafish neurogenesis. Trim69 was found to be expressed in zebrafish embryo brain at the early stages. Knockdown of trim69 led to deformed brain development, obvious signs of apoptosis present in the head, and decreased expression of neuronal differentiation and stem cell markers. This phenotype was rescued upon co-injection of human mRNA together along with the trim69 knockdown. Results of this study also showed an interaction between TRIM69 and c-Jun in human cells, and upon TRIM69 knock down c-Jun expression subsequently increased, whereas the over-expression of TRIM69 led to the down-regulation of c-Jun. Additionally, knockdown both c-Jun and trim69 can rescue the deformed brain, evident cellular apoptosis in the head and decreased expression of neuronal differentiation and stem cell markers. Overall, our results support a role for trim69 in the development of the zebrafish brain through ap-1 pathway. PMID:27050765

  13. Vacuum chamber thermal protection for the APS (Advanced Photon Source)

    SciTech Connect

    Kramer, S.L.; Crosbie, E.A.; Kim, S.; Wehrle, R.; Yoon, M.

    1989-01-01

    The addition of undulators and wigglers into synchrotron storage rings created new problems in terms of protecting the integrity of the ring vacuum chamber. If the photon beam from these devices were missteered into striking an inadequately cooled section of the storage ring vacuum chamber, the structural strength might be reduced sufficiently that the vacuum envelope could be penetrated, resulting in long downtime of the storage ring. The new generation of high-energy synchrotron light sources will produce photon beams of such high power density that cooling of the vacuum chamber will not prevent a potential penetration of the vacuum envelope, and other methods of preventing this occurrence will be required. Since active methods will be used to ensure that the beams are delivered to beam lines for users during normal operation, there is a need for passive protection methods during non-routine operation, such as turning on new beam lines, injection, etc., when the active systems may be disabled. In addition, the passive methods could prevent the problem from arising and provide the rapid time response necessary for the highest power beams, a property that might not be easily and reliably provided by active methods during the early operation of these machines. This paper summarizes the results of a task group that studied the problem and outlines passive methods of protection for the Advanced Photon Source (APS). 2 refs., 3 figs., 1 tab.

  14. FAST INJECTION SYSTEM R&D FOR THE APS UPGRADE

    SciTech Connect

    Lenkszus, F.; Carwardine, J.; Cours, A.; Decker, G.; Morrison, L.; Sun, X.; Westferro, F.; Yao, C. Y.; Krasnykh, Anatoly

    2015-06-01

    The MBA upgrade for the APS will operate with bunch swap out and on axis injection. The planned 324 bunch fill pattern places difficult demands on the injection and extraction kickers. The present concept uses dual stripline kickers driven by high Voltage pulsers. Minimizing perturbation on adjacent bunches requires very fast rise and fall times with relatively narrow ~20 nsec, 15 kV pulses. To achieve these requirements we have initiated a multifaceted R&D program. The R&D includes the HV pulser, stripline kicker and HV feedthrough. We have purchased a commercial dual channel HV pulser and are evaluating its performance and reliability. In addition, we are investigating the feasibility of using nonlinear ferrite loaded coaxial cables (shockwave transmission line) to sharpen the leading and trailing edges of high voltage pulses. We are also developing a prototype kicker and high voltage feedthrough. The requirements for injection and extraction, progress on prototype development and results of our HV pulser investigations will be reported.

  15. A quantum network with atoms and photons (QNET-AP)

    NASA Astrophysics Data System (ADS)

    Meyers, Ronald E.; Lee, Patricia; Deacon, Keith S.; Tunick, Arnold; Quraishi, Qudsia; Stack, Daniel

    2012-10-01

    Enabling secure communication, unparalleled computing capabilities, and fundamental nonlocality physics exploration, the development of quantum repeaters is the key quantum information processing technology advance needed for implementing real world quantum networks beyond the laboratory environment. Currently, components exist for intra-laboratory quantum networks but no system exists for connecting distant ( 1 km ) quantum memories in the real world. We present a physics analysis of quantum repeater network designs for intracity optical fiber connections between nodes based on atomic memories and linear optics. Long distances will necessitate the use of (1) two-photon Hong-Ou-Mandel style interference between atomic ensembles for entanglement swapping, and (2) photonic qubit wavelength conversion between atomic emissions and photons at telecommunication wavelengths in fiber. We report on our experimental progress towards implementing A Quantum Network with Atoms and Photons (QNET-AP), a quantum repeater network test-bed, between the US Army Research Laboratory (ARL) and the Joint Quantum Institute (JQI) of the National Institute of Standards and Technology (NIST) and the University of Maryland (UMD).

  16. Absolute properties of the eclipsing binary star AP Andromedae

    SciTech Connect

    Sandberg Lacy, Claud H.; Torres, Guillermo; Fekel, Francis C.; Muterspaugh, Matthew W. E-mail: gtorres@cfa.harvard.edu E-mail: matthew1@coe.tsuniv.edu

    2014-06-01

    AP And is a well-detached F5 eclipsing binary star for which only a very limited amount of information was available before this publication. We have obtained very extensive measurements of the light curve (19,097 differential V magnitude observations) and a radial velocity curve (83 spectroscopic observations) which allow us to fit orbits and determine the absolute properties of the components very accurately: masses of 1.277 ± 0.004 and 1.251 ± 0.004 M {sub ☉}, radii of 1.233 ± 0.006 and 1.1953 ± 0.005 R {sub ☉}, and temperatures of 6565 ± 150 K and 6495 ± 150 K. The distance to the system is about 400 ± 30 pc. Comparison with the theoretical properties of the stellar evolutionary models of the Yonsei-Yale series of Yi et al. shows good agreement between the observations and the theory at an age of about 500 Myr and a slightly sub-solar metallicity.

  17. Tandem Differential Mobility Analyzer/Aerodynamic Particle Sizer (APS) Handbook

    SciTech Connect

    Collins, D

    2010-06-18

    The tandem differential mobility analyzer (TDMA) is a single instrument that cycles through a series of complementary measurements of the physical properties of size-resolved submicron particles. In 2008, the TDMA was augmented through the addition of an aerodynamic particle sizer (APS), which extends the upper limit of the measured size distribution into the supermicron range. These two instruments are operated in parallel, but because they are controlled by a common computer and because the size distributions measured by the two are integrated in the produced datastreams, they are described together here. Throughout the day, the TDMA sequentially measures submicron aerosol size distributions and size-resolved hygroscopic growth distributions. More specifically, the instrument is operated as a scanning DMA to measure size distributions and as a TDMA to measure size-resolved hygroscopicity. A typical measurement sequence requires roughly 45 minutes. Each morning additional measurements are made of the relative humidity (RH) dependent hygroscopicity and temperature-dependent volatility of size-resolved particles. When the outside temperature and RH are within acceptable ranges, the hydration state of size-resolved particles is also characterized. The measured aerosol distributions complement the array of aerosol instruments in the Aerosol Observing System (AOS) and provide additional details of the light-scattering and cloud-nucleating characteristics of the aerosol.

  18. Vibration study of the APS magnet support assemblies

    SciTech Connect

    Wambsganss, M.W.; Jendrzejczyk, J.A.; Chen, S.S.

    1990-11-01

    Stability of the positron closed orbit is a requirement for successful operation of the Advanced Photon Source. The fact that vibration of the storage ring quadrupole magnets can lead to distortion of the positron closed orbit and to potentially unacceptable beam emittance growth provides the motivation for the subject studies. Low frequency vibrations can be controlled with steering magnets using feedback systems, provided the vibration amplitudes are within the dynamic range of the controllers. High frequency vibration amplitudes, on the other hand, are out of the range of the controller and, therefore must be limited to ensure the emittance growth will not exceed a prescribed value. Vibration criteria were developed based on the requirement that emittance growth be limited to 10 percent. Recognizing that the quadrupole magnets have the most significant effect, three different scenarios were considered: vibration of a single quadrupole within the storage ring, random vibration of all the quadrupoles in the ring, and the hypothetical case of a plane wave sweeping across the site and the quadrupoles following the motion of the plane wave. The maximum allowable peak vibration amplitudes corresponding to these three vibration scenarios are given. The criteria associated with the passage of a plane wave is dependent on wavelength, or, alternatively, on frequency given the wave speed. The wave speed used is that measured as a part of the geotechnical investigation at the APS site.

  19. CDKN2A/p16 in ependymomas.

    PubMed

    Bortolotto, S; Chiadò-Piat, L; Cavalla, P; Bosone, I; Mauro, A; Schiffer, D

    2001-08-01

    Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.

  20. Beam Stability R&D for the APS MBA Upgrade

    SciTech Connect

    Sereno, Nicholas S.; Arnold, Ned D.; Bui, Hanh D.; Carwardine, J.; Decker, Glenn; Emery, Louis; Farnsworth, Richard; Keane, Robert T.; Lenkszus, F.; Lill, Robert M.; Lipa, Robert A.; Vesseli, S.; Xu, Shifu; Yang, Bingxin

    2015-01-01

    Beam diagnostics required for the APS Multi-bend acromat (MBA) are driven by ambitious beam stability requirements. The major AC stability challenge is to correct rms beam motion to 10% the rms beam size at the insertion device source points from0.01 to 1000 Hz. The vertical plane represents the biggest challenge forAC stability, which is required to be 400 nm rms for a 4-micron vertical beam size. In addition to AC stability, long-term drift over a period of seven days is required to be 1 micron or less. Major diagnostics R&D components include improved rf beam position processing using commercially available FPGA-based BPM processors, new X-ray beam position monitors based on hard X-ray fluorescence from copper and Compton scattering off diamond, mechanical motion sensing to detect and correct long-term vacuum chamber drift, a new feedback system featuring a tenfold increase in sampling rate, and a several-fold increase in the number of fast correctors and BPMs in the feedback algorithm. Feedback system development represents a major effort, and we are pursuing development of a novel algorithm that integrates orbit correction for both slow and fast correctors down to DC simultaneously. Finally, a new data acquisition system (DAQ) is being developed to simultaneously acquire streaming data from all diagnostics as well as the feedback processors for commissioning and fault diagnosis. Results of studies and the design effort are reported.

  1. 75 FR 20774 - Establishment of Class E Airspace; Fort A.P. Hill, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Fort A.P. Hill, VA... Register December 7, 2009 that establishes Class E airspace at Fort A.P. Hill, VA. DATES: Effective Date..., Eastern Service Center, Federal Aviation Administration, P.O. Box 20636, Atlanta, Georgia 30320;...

  2. What I Did Instead of Summer Vacation: A Study of the APS Summer School Program.

    ERIC Educational Resources Information Center

    Albuquerque Public Schools, NM.

    This report summarizes the findings of a 1985 study of the Albuquerque Public Schools (APS) summer school program. Statistics, charts and survey results provide a picture of the student population, school financial situation, course offerings, participant attitudes, etc. The APS summer school is self-supporting, but tuition is rising rapidly and…

  3. Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network.

    PubMed

    de Crozé, Noémie; Maczkowiak, Frédérique; Monsoro-Burq, Anne H

    2011-01-04

    The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.

  4. Development of cotton gin PM2.5 emission factors for EPA’S AP-42

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Compilation of Air Pollution Emission Factors (AP-42) emission factors are assigned ratings, from A (Excellent) to E (Poor), based on the quality of data used to develop them. AP-42 currently contains no PM2.5 cotton gin emission factors. In an effort to develop science-based data for regulating...

  5. APS: 125 Years of Progress of Physiology as a Scientific Discipline and a Profession

    ERIC Educational Resources Information Center

    Carroll, Robert G.; Frank, Martin; Ra'anan, Alice; Matyas, Marsha L.

    2013-01-01

    The Experimental Biology 2012 meeting in San Diego, CA, included events to celebrate the 125th anniversary of the founding of the American Physiological Society (APS) and reflect on the recent accomplishments of the society. Most of the APS activities in the past quarter century were guided by a series of strategic plans. Membership in the APS…

  6. Glutathione peroxidase-1 inhibits UVA-induced AP-2{alpha} expression in human keratinocytes

    SciTech Connect

    Yu Lei; Venkataraman, Sujatha; Coleman, Mitchell C.; Spitz, Douglas R.; Wertz, Philip W.; Domann, Frederick E. . E-mail: frederick-domann@uiowa.edu

    2006-12-29

    In this study, we found a role for H{sub 2}O{sub 2} in UVA-induced AP-2{alpha} expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2{alpha}, but also caused accumulation of H{sub 2}O{sub 2} in the cell culture media, and H{sub 2}O{sub 2} by itself could induce the expression of AP-2{alpha}. By catalyzing the removal of H{sub 2}O{sub 2} from cells through over-expression of GPx-1, induction of AP-2{alpha} expression by UVA was abolished. Induction of transcription factor AP-2{alpha} by UVA had been previously shown to be mediated through the second messenger ceramide. We found that not only UVA irradiation, but also H{sub 2}O{sub 2} by itself caused increases of ceramide in HaCaT cells, and C2-ceramide added to cells induced the AP-2{alpha} signaling pathway. Finally, forced expression of GPx-1 eliminated UVA-induced ceramide accumulation as well as AP-2{alpha} expression. Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2{alpha} expression by suppressing the accumulation of H{sub 2}O{sub 2}.

  7. The Freshman Nine: Helping High School Freshmen Be Successful in AP Human Geography

    ERIC Educational Resources Information Center

    Garner, Jennifer

    2012-01-01

    Teaching AP Human Geography to freshmen seems like a daunting task and while there are many arguments both for and against offering the course to freshmen, for many teachers it is reality. In this article, the author offers nine tips to help high school freshmen be successful in the course and on the AP exam.

  8. 77 FR 8848 - Application for New Awards; Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... Application for New Awards; Advanced Placement (AP) Test Fee Program AGENCY: Office of Elementary and Secondary Education, Department of Education. ACTION: Notice. Overview Information: Advanced Placement Test.... Full Text of Announcement I. Funding Opportunity Description Purpose of Program: The AP Test...

  9. 78 FR 19691 - Applications for New Awards; Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... Applications for New Awards; Advanced Placement (AP) Test Fee Program AGENCY: Office of Elementary and Secondary Education, Department of Education. ACTION: Notice. Overview Information Advanced Placement Test... Announcement I. Funding Opportunity Description Purpose of Program: The AP Test Fee program awards grants...

  10. The History of the APS Shock Compression of Condensed Matter Topical Group

    SciTech Connect

    Forbes, J W

    2001-05-02

    In order to provide broader scientific recognition and to advance the science of shock compressed condensed matter, a group of American Physical Society (APS) members worked within the Society to make this field an active part of the APS. Individual papers were presented at APS meetings starting in the 1940's and shock wave sessions were organized starting with the 1967 Pasadena meeting. Shock wave topical conferences began in 1979 in Pullman, WA. Signatures were obtained on a petition in 1984 from a balanced cross-section of the shock wave community to form an APS Topical Group (TG). The APS Council officially accepted the formation of the Shock Compression of Condensed Matter (SCCM) TG at its October 1984 meeting. This action firmly aligned the shock wave field with a major physical science organization. Most early topical conferences were sanctioned by the APS while those held after 1992 were official APS meetings. The topical group organizes a shock wave topical conference in odd numbered years while participating in shock wave/high pressure sessions at APS general meetings in even numbered years.

  11. History of the APS Topical Group on Shock Compression of Condensed Matter

    SciTech Connect

    Forbes, J W

    2001-10-19

    In order to provide broader scientific recognition and to advance the science of shock compressed condensed matter, a group of American Physical Society (APS) members worked within the Society to make this field an active part of the APS. Individual papers were presented at APS meetings starting in the 1940's and shock wave sessions were organized starting with the 1967 Pasadena meeting. Shock wave topical conferences began in 1979 in Pullman, WA. Signatures were obtained on a petition in 1984 from a balanced cross-section of the shock wave community to form an APS Topical Group (TG). The APS Council officially accepted the formation of the Shock Compression of Condensed Matter (SCCM) TG at its October 1984 meeting. This action firmly aligned the shock wave field with a major physical science organization. Most early topical conferences were sanctioned by the APS while those held after 1992 were official APS meetings. The topical group organizes a shock wave topical conference in odd numbered years while participating in shock wavehigh pressure sessions at APS general meetings in even numbered years.

  12. The 8th Annual AP[R] Report to the Nation

    ERIC Educational Resources Information Center

    College Board, 2012

    2012-01-01

    In classrooms around the country, AP (Advanced Placement) teachers are preparing students for tomorrow by teaching them how to think and learn today. AP students learn to construct solid arguments, test theories, and see many sides of an issue--the kind of thinking that solves tough problems both in and outside the classroom, in college and…

  13. AP-1 family members act with Sox9 to promote chondrocyte hypertrophy.

    PubMed

    He, Xinjun; Ohba, Shinsuke; Hojo, Hironori; McMahon, Andrew P

    2016-08-15

    An analysis of Sox9 binding profiles in developing chondrocytes identified marked enrichment of an AP-1-like motif. Here, we have explored the functional interplay between Sox9 and AP-1 in mammalian chondrocyte development. Among AP-1 family members, Jun and Fosl2 were highly expressed within prehypertrophic and early hypertrophic chondrocytes. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) showed a striking overlap in Jun- and Sox9-bound regions throughout the chondrocyte genome, reflecting direct binding of each factor to the same enhancers and a potential for protein-protein interactions within AP-1- and Sox9-containing complexes. In vitro reporter analysis indicated that direct co-binding of Sox9 and AP-1 at target motifs promoted gene activity. By contrast, where only one factor can engage its DNA target, the presence of the other factor suppresses target activation consistent with protein-protein interactions attenuating transcription. Analysis of prehypertrophic chondrocyte removal of Sox9 confirmed the requirement of Sox9 for hypertrophic chondrocyte development, and in vitro and ex vivo analyses showed that AP-1 promotes chondrocyte hypertrophy. Sox9 and Jun co-bound and co-activated a Col10a1 enhancer in Sox9 and AP-1 motif-dependent manners consistent with their combined action promoting hypertrophic gene expression. Together, the data support a model in which AP-1 family members contribute to Sox9 action in the transition of chondrocytes to the hypertrophic program.

  14. PSAT Component Scores as a Predictor of Success on AP Exam Performance for Diverse Students

    ERIC Educational Resources Information Center

    Richardson, Cristianne C.; Gonzalez, Alejandro; Leal, Lonnie; Castillo, Mary Z.; Carman, Carol A.

    2016-01-01

    While studies have shown the positive effect of the Advanced Placement (AP) program on college readiness, there are still barriers preventing minority and low socioeconomic status (SES) students who possess high academic potential from participating in the opportunity that AP courses offer. One tool that could help identify students for…

  15. Growth and Achievement Trends of Advanced Placement (AP) Exams in American High Schools

    ERIC Educational Resources Information Center

    Judson, Eugene; Hobson, Angela

    2015-01-01

    This exploratory study examined and compared overall trends in growth and student achievement of the Advanced Placement (AP) program. Using data from the past two decades, analyses indicated there has been steady and extensive growth of AP participation, particularly among underclassmen and some minority groups. However, overall achievement, as…

  16. Environmental and Sustainable Technology Evaluation: Mold-Resistant Armacell Insulation--Armacell LLC, AP Armaflex Black

    EPA Science Inventory

    The ESTE test program measured the mold resistance of Armacell AP Armaflex Black insulation. Tests for emissions of VOCs and formaldehyde were also performed. AP Armaflex Roll Insulation is a black flexible closed-cell, fiber-free elastomeric thermal insulation. The expanded clos...

  17. Advanced Placement Strategy: A Framework for Identifying School-Level Barriers to AP Success. Policy Brief

    ERIC Educational Resources Information Center

    Batiwalla, Mary

    2014-01-01

    In 2013, Tennessee counted nearly 7,000 students in the senior cohort whose academic skills when they entered high school suggested they were on track to earn college credits through Advanced Placement (AP) exams. Yet just over half of these students actually graduated with an AP credit, and less than a third of the economically disadvantaged…

  18. WCPSS Advanced Placement (AP) Results, 2010-11. D&A Report No. 11.25

    ERIC Educational Resources Information Center

    Gilleland, Kevin

    2012-01-01

    One method of delivering college-level coursework to high school students is through the Advanced Placement (AP) program. Many colleges and universities provide credit to students who earn a qualifying score on any of the 34 available AP exams offered by the College Board. All qualified comprehensive high schools in the Wake County Public School…

  19. Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

    NASA Technical Reports Server (NTRS)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

    The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

  20. Foundations for College and Beyond: Looking Back on AP Art History

    ERIC Educational Resources Information Center

    Schoenbohm, Laurel

    2013-01-01

    It was years after this author's AP Art History course in high school, and two years after college. She and some friends decided to fill a day during the Thanksgiving visits appreciating fine art. Prior to that AP course her senior year of high school, touring an art museum had seemed like the equivalent of going to the dentist. But after…

  1. Coming Soon: CADRE (Career Advancement and Development Resources and Education) website for all APS members

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Council of the American Phytopathological Society (APS) approved an initiative in February 2013 to create a web resource called CADRE (Career Advancement and Development Resources and Education). CADRE is to provide APS members an archive of articles, videos, and webinars about a variety of prof...

  2. An RbAp48-like gene regulates adult stem cells in planarians.

    PubMed

    Bonuccelli, Lucia; Rossi, Leonardo; Lena, Annalisa; Scarcelli, Vittoria; Rainaldi, Giuseppe; Evangelista, Monica; Iacopetti, Paola; Gremigni, Vittorio; Salvetti, Alessandra

    2010-03-01

    Retinoblastoma-associated proteins 46 and 48 (RbAp46 and RbAp48) are factors that are components of different chromatin-modelling complexes, such as polycomb repressive complex 2, the activity of which is related to epigenetic gene regulation in stem cells. To date, no direct findings are available on the in vivo role of RbAp48 in stem-cell biology. We recently identified DjRbAp48 - a planarian (Dugesia japonica) homologue of human RBAP48 - expression of which is restricted to the neoblasts, the adult stem cells of planarians. In vivo silencing of DjRbAp48 induces lethality and inability to regenerate, even though neoblasts proliferate and accumulate after wounding. Despite a partial reduction in neoblast number, we were always able to detect a significant number of these cells in DjRbAp48 RNAi animals. Parallel to the decrease in neoblasts, a reduction in the number of differentiated cells and the presence of apoptotic-like neoblasts were detectable in RNAi animals. These findings suggest that DjRbAp48 is not involved in neoblast maintenance, but rather in the regulation of differentiation of stem-cell progeny. We discuss our data, taking into account the possibility that DjRbAp48 might control the expression of genes necessary for cell differentiation by influencing chromatin architecture.

  3. Ten Things to Consider When Teaching AP U.S. History

    ERIC Educational Resources Information Center

    Libresco, Andrea S.

    2013-01-01

    This article describes 10 recommendations for creativity, higher-order thinking, and meaningful learning activities that can be used to guide teachers in constructing an engaging AP course: (1) Be on the committee that decides how students will be selected for AP; (2) Maximize time and connections through blocks of time with an English colleague;…

  4. Preparing for the AP Exam: The Dangers of Teaching to the Test.

    ERIC Educational Resources Information Center

    Chu, Jonathan M.

    2000-01-01

    Argues that poor student performance on the Advanced Placement (AP) U.S. history examination is due to poor preparation for the exam and the misuse of the AP examination to measure teacher effectiveness and school quality. States that teaching methods must change to enable students to see the relationships among facts in history. (CMK)

  5. Back to the Future: Merit or Equity in AP Social Studies?

    ERIC Educational Resources Information Center

    Stevens, Robert

    2013-01-01

    In an effort to address severe budget deficits at both the state and local levels, schools and educational programs are being asked to trim budgets. The Advanced Placement Program is one program that will certainly be scrutinized. This article presents a general overview of AP social studies, a brief history of the AP social studies program, and…

  6. α2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction

    PubMed Central

    Kanno, Yosuke; Kawashita, Eri; Kokado, Akiko; Kuretake, Hiromi; Ikeda, Kanako; Okada, Kiyotaka; Seishima, Mariko; Ueshima, Shigeru; Matsuo, Osamu; Matsuno, Hiroyuki

    2014-01-01

    Renal fibrosis is the final common pathway of a wide variety of chronic kidney diseases. Myofibroblast formation via the differentiation of from tissue-resident fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs), and epithelial-to-mesenchymal transition (EMT) is known to play a pivotal role in the development of renal fibrosis. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of alpha 2-antiplasmin (α2AP) in myofibroblast formation and the development of renal fibrosis. We observed the development of renal fibrosis using unilateral ureteral obstruction (UUO). α2AP had accumulated in the UUO-induced obstructed kidneys and α2AP deficiency attenuated UUO-induced renal fibrosis in mice. The degree of myofibroblast formation in the obstructed kidneys of α2AP−/− mice was less than that in α2AP+/+ mice. In vitro, α2AP induced myofibroblast formation in renal tubular epithelial cells (RTECs), renal fibrosblasts, and bone marrow-derived mesenchymal stem cells (MSCs). α2AP also induced the production of TGF-β, which is known to be a key regulator of myofibroblast formation and fibrosis. α2AP-induced the TGF-β production was significantly reduced by SP600125, c-Jun N-terminal kinase (JNK) specific inhibitor. Our findings suggest that α2AP induces myofibroblast formation in the obstructed kidneys, and mediates the development of renal fibrosis. PMID:25095732

  7. Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1.

    PubMed

    Ren, Xuefeng; Farías, Ginny G; Canagarajah, Bertram J; Bonifacino, Juan S; Hurley, James H

    2013-02-14

    AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. AP-1 recruitment to these compartments requires Arf1-GTP. The crystal structure of the tetrameric core of AP-1 in complex with Arf1-GTP, together with biochemical analyses, shows that Arf1 activates cargo binding by unlocking AP-1. Unlocking is driven by two molecules of Arf1 that bridge two copies of AP-1 at two interaction sites. The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the β1 subunit of one AP-1 complex, while the back side of Arf1 binds to the central part of the γ subunit trunk of a second AP-1 complex. A third Arf1 interaction site near the N terminus of the γ subunit is important for recruitment, but not activation. These observations lead to a model for the recruitment and activation of AP-1 by Arf1.

  8. RNF20 promotes the polyubiquitination and proteasome-dependent degradation of AP-2α protein.

    PubMed

    Ren, Peng; Sheng, Zhifeng; Wang, Yijun; Yi, Xin; Zhou, Qiuzhi; Zhou, Jianlin; Xiang, Shuanglin; Hu, Xiang; Zhang, Jian

    2014-02-01

    Transcription factor activator protein 2α (AP-2α) is a negative regulator of adipogenesis by repressing the transcription of CCAAT/enhancer binding protein (C/EBPα) gene. During adipogenesis, AP-2α is degraded, leading to transcriptional up-regulation of C/EBPα. However, the mechanism for AP-2α degradation is not clear. Here, using immunoprecipitation assay and mass spectrometry, we identified ring finger protein 20 (RNF20) as an AP-2α-interacting protein in 3T3-L1 preadipocytes. RNF20 has been proved to be an E3 ubiquitin ligase for both histone H2B and tumor suppressor ErbB3-binding protein 1 (Ebp1). In this study, we demonstrated that RNF20 co-localized and interacted with AP-2α, and promoted its polyubiquitination and proteasome-dependent degradation. Over-expression of RNF20 inhibited the activity of AP-2α and rescued the C/EBPα expression which was inhibited by AP-2α. These results suggested that RNF20 may play roles in adipocyte differentiation by stimulating ubiquitin-proteasome-dependent degradation of AP-2α.

  9. Understanding and Using the New Guided-Inquiry AP Chemistry Laboratory Manual

    ERIC Educational Resources Information Center

    Cacciatore, Kristen L.

    2014-01-01

    To support teaching and learning in the advanced placement (AP) chemistry laboratory, the College Board published a laboratory manual, "AP Chemistry Guided-Inquiry Experiments: Applying the Science Practices," in 2013 as part of the redesigned course. This article provides a discussion of the rationale for the existence of the manual as…

  10. AP-2γ Induces p21 Expression, Arrests Cell Cycle, and Inhibits the Tumor Growth of Human Carcinoma Cells1

    PubMed Central

    Li, Hualei; Goswami, Prabhat C; Domann, Frederick E

    2006-01-01

    Abstract Activating enhancer-binding protein 2γ (AP-2γ) is a member of the developmentally regulated AP-2 transcription factor family that regulates the expression of many downstream genes. Whereas the effects of AP-2α overexpression on cell growth are fairly well established, the cellular effects of AP-2γ overexpression are less well studied. Our new findings show that AP-2γ significantly upregulates p21 mRNA and proteins, inhibits cell growth, and decreases clonogenic survival. Cell cycle analysis revealed that forced AP-2γ expression induced G1-phase arrest, decreased DNA synthesis, and decreased the fraction of cells in S phase. AP-2γ expression also led to cyclin D1 repression, decreased Rb phosphorylation, and decreased E2F activity in breast carcinoma cells. AP-2γ binding to the p21 promoter was observed in vivo, and the absence of growth inhibition in response to AP-2γ expression in p21 (-/-) cells demonstrated that p21 caused, at least in part, AP-2-induced cell cycle arrest. Finally, the tumor growth of human breast carcinoma cells in vivo was inhibited by the expression of AP-2γ relative to empty vector-infected cells, suggesting that AP-2γ acts as a tumor suppressor. In summary, expression of either AP-2γ or AP-2α inhibited breast carcinoma cell growth; thus, these genes may be therapeutic targets for breast cancer. PMID:16867219

  11. Binding of AP-2 adaptor complex to brain membrane is regulated by phosphorylation of proteins

    SciTech Connect

    Alberdi, A. . E-mail: aalberdi@fcm.uncu.edu.ar; Sartor, T.; Sosa, M.A.

    2005-05-13

    Phosphorylation of proteins appears as a key process in early steps of clathrin coated vesicle formation. Here, we report that treatment of post-nuclear fraction with alkaline phosphatase induced redistribution of {alpha} subunits of AP-2 adaptor complex to cytosol and this effect was higher in the {alpha}2 subunit. A high serine phosphorylation status of {alpha} subunits correlated with the higher affinity of AP-2 to membranes. Using a simple binding assay, where membranes were incubated with either purified adaptors or cytosols, we observed an inhibitory effect of tyrphostin, a tyrosine kinase inhibitor, on the binding of AP-2 to membranes, but also an unexpected decrease induced by the phosphatase inhibitor cyclosporine. We also show an inhibitory effect of ATP mediated by cytosolic proteins, although it could not be related to the phosphorylation of AP-2, suggesting an action upstream a cascade of phosphorylations that participate in the regulation of the assembly of AP-2 to membranes.

  12. Glossary for the implementation of Health in All Policies (HiAP).

    PubMed

    Freiler, Alix; Muntaner, Carles; Shankardass, Ketan; Mah, Catherine L; Molnar, Agnes; Renahy, Emilie; O'Campo, Patricia

    2013-12-01

    Health in All Policies (HiAP) is becoming increasingly popular as a governmental strategy to improve population health by coordinating action across health and non-health sectors. A variety of intersectoral initiatives may be used in HiAP that frame health determinants as the bridge between policies and health outcomes. The purpose of this glossary is to present concepts and terms useful in understanding the implementation of HiAP as a cross-sectoral policy. The concepts presented here were applied and elaborated over the course of case studies of HiAP in multiple jurisdictions, which used key informant interviews and the systematic review of literature to study the implementation of specific HiAP initiatives.

  13. The γ/σ1 and α/σ2 Hemicomplexes of Clathrin Adaptors AP-1 and AP-2 Harbor the Dileucine Recognition Site

    PubMed Central

    Doray, Balraj; Lee, Intaek; Knisely, Jane; Bu, Guojun

    2007-01-01

    The clathrin adaptors AP-1 and AP-2 bind cargo proteins via two types of motifs: tyrosine-based Yxxφ and dileucine-based [DE]XXXL[LI]. Although it is well established that Yxxφ motifs bind to the μ subunits of AP-1 or AP-2, dileucine motifs have been reported to bind to either the μ or β subunits of these adaptors as well as the γ/σ1 hemicomplex of AP-1. To clarify this controversy, the various subunits of AP-1 and AP-2 were expressed individually and in hemicomplex form in insect cells, and they were used in glutathione S-transferase pull-down assays to determine their binding properties. We report that the γ/σ1 or α/σ2 hemicomplexes bound the dileucine-based motifs of several proteins quite strongly, whereas binding by the β1/μ1 and β2/μ2 hemicomplexes, and the individual β or μ subunits, was extremely weak or undetectable. The γ/σ1 and α/σ2 hemicomplexes displayed substantial differences in their preference for particular dileucine-based motifs. Most strikingly, an aspartate at position −4 compromised binding to the γ/σ1 hemicomplex, whereas minimally affecting binding to α/σ2. There was an excellent correlation between binding to the α/σ2 hemicomplex and in vivo internalization mediated by the dileucine-based sorting signals. These findings provide new insights into the trafficking mechanisms of D/EXXXL[LI]-mediated sorting signals. PMID:17360967

  14. Soluble TNF Regulates TACE via AP-2α Transcription Factor in Mouse Dendritic Cells.

    PubMed

    Ge, Lisheng; Vujanovic, Nikola L

    2017-01-01

    Dendritic cells (DCs), the essential immunoregulatory and APCs, are major producers of the central mediator of inflammation, soluble TNF-α (sTNF). sTNF is generated by TNF-α converting enzyme (TACE) proteolytic release of the transmembrane TNF (tmTNF) ectodomain. The mechanisms of TACE and sTNF regulation in DCs remain elusive. This study newly defines that sTNF regulates TACE in mouse DCs by engaging the AP-2α transcription factor. We found that the expression of AP-2α was higher, whereas the expression and activity of TACE were lower, in wild-type DCs (wtDCs) than in TNF knockout (TNFko) DCs. Exogenous sTNF rapidly and simultaneously induced increases of AP-2α expression and decreases of TACE expression and activity in wtDCs and TNFko DCs, indicating that AP-2α and TACE are inversely dependent on sTNF and are functionally associated. To define this functional association, we identified an AP-2α binding site in TACE promoter and demonstrated, using EMSAs and chromatin immunoprecipitation assays, that AP-2α could bind to TACE promoter in a TNF-dependent manner. Additionally, sTNF simultaneously enhanced AP-2α expression and decreased TACE promoter luciferase activity in DCs. Similarly, transfection of AP-2α cDNA decreased TACE promoter luciferase activity, TACE expression, and TACE enzymatic activity in wtDCs or TNFko DCs. In contrast, transfection of AP-2α small interfering RNA increased TACE promoter luciferase activity, TACE expression, and TACE enzymatic activity in wtDCs. These results show that TACE is a target of, and is downregulated by, sTNF-induced AP-2α transcription factor in DCs.

  15. Interaction of amphiphysins with AP-1 clathrin adaptors at the membrane.

    PubMed

    Huser, Sonja; Suri, Gregor; Crottet, Pascal; Spiess, Martin

    2013-02-15

    The assembly of clathrin/AP (adaptor protein)-1-coated vesicles on the trans-Golgi network and endosomes is much less studied than that of clathrin/AP-2 vesicles at the plasma membrane for endocytosis. In vitro, the association of AP-1 with protein-free liposomes had been shown to require phosphoinositides, Arf1 (ADP-ribosylation factor 1)-GTP and additional cytosolic factor(s). We have purified an active fraction from brain cytosol and found it to contain amphiphysin 1 and 2 and endophilin A1, three proteins known to be involved in the formation of AP-2/clathrin coats at the plasma membrane. Assays with bacterially expressed and purified proteins showed that AP-1 stabilization on liposomes depends on amphiphysin 2 or the amphiphysin 1/2 heterodimer. Activity is independent of the SH3 (Src homology 3) domain, but requires interaction of the WDLW motif with γ-adaptin. Endogenous amphiphysin in neurons and transfected protein in cell lines co-localize perinuclearly with AP-1 at the trans-Golgi network. This localization depends on interaction of clathrin and the adaptor sequence in the amphiphysins and is sensitive to brefeldin A, which inhibits Arf1-dependent AP-1 recruitment. Interaction between AP-1 and amphiphysin 1/2 in vivo was demonstrated by co-immunoprecipitation after cross-linking. These results suggest an involvement of amphiphysins not only with AP-2 at the plasma membrane, but also in AP-1/clathrin coat formation at the trans-Golgi network.

  16. Foreword: 18th Aps-Sccm and 24th Airapt

    NASA Astrophysics Data System (ADS)

    Collins, Gilbert; Moore, David S.; Yoo, Choong-Shik

    2014-05-01

    This second joint conference between the APS Topical Group on Shock Compression of Condensed Matter and the International Association for the Advancement of High Pressure Science and Technology (AIRAPT) demonstrates that static and dynamic compression of condensed matter continues to be a vibrant field of science and engineering. It is also by its nature an interdisciplinary field, incorporating chemistry, materials science, solid mechanics, plasma physics, and condensed matter physics, and utilizes theoretical, computational, and experimental tools. Recent years have brought about many advances in loading platforms, diagnostics, and computations that are leading to the emergence of many new avenues of research. These advances are also breathing new life into traditional topics such as equations of state, phase transformations, and chemistry at extreme conditions. The plenary lectures by Gennady Kanel, Karl Syassen, David Ceperley, Jon Eggert, Duck Young Kim, and Richard Kraus spanned the disciplines of static and dynamic high pressure physics and illustrated the breadth of the field. They also showed that interesting and important problems remain for researchers of the future to solve. The main guiding principal in the organization of this conference was to intertwine static and dynamical experimental alongside computational and theoretical studies of similar materials. To achieve this goal, we arranged the conference to include static, dynamic, and computational components in the same sessions, quite often taking presenters out of their comfort zone. The three special sessions on Deep Carbon Budget (organized by Giulia Galli and Rus Hemley), High Energy Density Materials (organized by Raymond Jeanloz and Jon Eggert), and Dynamic Response of Materials (organized by Yogendra Gupta and John Sarrao) furthered this guiding principal. We also endeavored to represent the breadth of static and dynamic high pressure science and technology, notably beyond that done at

  17. Authenticated, private, and secured smart cards (APS-SC)

    NASA Astrophysics Data System (ADS)

    Szu, Harold; Mehmood, Amir

    2006-04-01

    From historical perspective, the recent advancements in better antenna designs, low power circuitry integrations and inexpensive fabrication materials have made possible a miniature counter-measure against Radar, a clutter behaving like a fake target return called Digital Reflection Frequency Modulation (DRFM). Such a military counter-measure have found its way in the commerce as a near field communication known as Radio Frequency Identification (RFID), a passive or active item tag T attached to every readable-writable Smart Card (SC): Passports ID, medical patient ID, biometric ID, driver licenses, book ID, library ID, etc. These avalanche phenomena may be due to the 3 rd Gen phones seeking much more versatile & inexpensive interfaces, than the line-of-sight bar-code optical scan. Despite of the popularity of RFID, the lacking of Authenticity, Privacy and Security (APS) protection restricted somewhat the wide spread commercial, financial, medical, legal, and militarily applications. Conventional APS approach can obfuscate a private passkey K of SC with the tag number T or the reader number R, or both, i.e. only T*K or R*K or both will appear on them, where * denotes an invertible operation, e.g. EXOR, but not limited to it. Then, only the authentic owner, knowing all, can inverse the operation, e.g. EXOR*EXOR= I to find K. However, such an encryption could be easily compromised by a hacker seeking exhaustively by comparison based on those frequently used words. Nevertheless, knowing biological wetware lesson for power of pairs sensors and Radar hardware counter-measure history, we can counter the counter-measure DRFM, instead using one RFID tag per SD, we follow the Nature adopting two ears/tags, e.g. each one holding portions of the ID or simply two different ID's readable only by different modes of the interrogating reader, followed by brain central processor in terms of nonlinear invertible shufflers mixing two ID bits. We prefer to adopt such a hardware

  18. Renal effects of atriopeptin (AP) II in conscious SHR

    SciTech Connect

    Smits, J.F.; Debets, J.M.; Struyker-Boudier, H.A.; Daemen, M.J.

    1986-03-05

    Diuresis and natriuresis following APs has been suggested to depend upon increased renal blood flow (RBF). In a previous study, they found that APII infusions in conscious SHR decrease RBF. In this study, they report effects of APII on glomerular filtration rate (GFR) and renal excretory function in conscious SHR. Male SHR were equipped with arterial and venous catheters. Furthermore, a special catheter was implanted into the bladder to allow continuous urine sampling from conscious, freely moving rats. Animals were allowed at least 4 days to recover. In one group of SHR, APII (N=7) or saline (N=7) was infused to quantitate excretion of water, Na/sup +/, and K/sup +/. Two other groups of SHR (N=8 each) were infused with /sup 51/Cr-EDTA and /sup 125/I-PAH. GFR and renal plasma flow (ERPF) were calculated from urine and a mid-time plasma sample during APII or saline infusion. Following changes in infusion rates, urine from the first 5 min was discarded, after which a 10-min collection was made. APII (0.5-4 ..mu..g/kg/min) increased water, Na/sup +/ and K/sup +/ output maximally during 2 ..mu..g/kg/min. ERPF decreased from 10.7 +/- 1.1 ml/min to 7.9 +/- 0.5 ml/min. GFR did not change significantly. Filtration fraction increased from 24 +/- 1% to 33 +/- 2%. Fractional water excretion increased from 0.8 +/- 0.2% to 2.5 +/- 0.7%. Saline infusions did not affect renal function. The results indicate that in conscious SHR, APII causes diuresis and natriuresis which does not depend upon increased GFR, but, rather, upon a primary tubular effect.

  19. Synthesis of specific diastereomers of a DNA methylphosphonate heptamer, d(CpCpApApApCpA), and stability of base pairing with the normal DNA octamer d(TPGPTPTPTPGPGPC).

    PubMed Central

    Vyazovkina, E V; Savchenko, E V; Lokhov, S G; Engels, J W; Wickstrom, E; Lebedev, A V

    1994-01-01

    DNA methylphosphonates are candidate derivatives for use in antisense DNA therapy. Their efficacy is limited by weak hybridization. One hypothesis to explain this phenomenon holds that one configuration of the chiral methylphosphonate linkage, Rp, permits stronger base pairing than the other configuration, Sp. To test this hypothesis, four specific pairs of Rp and Sp diastereomers of the DNA methylphosphonate heptamer d(CpCpApApApCpA) were prepared by block coupling of different combinations of individual diastereomers of d(CpCpApA) and d(ApCpA). Each pair of the diastereomers of the heptamer was separated into individual diastereomes using affinity chromatography on a Lichrosorb-NH2 silica column with a covalently attached complementary normal DNA octamer, d(pTpGpTpTpTpGpGpC). The stabilities of complementary complexes of phosphodiester d(TpGpTpTpTpGpGpC) with 8 individual diastereomers of methylphosphonate d(CpCpApApApCpA) were studied by measuring their melting temperatures (Tm). A direct correlation of Tm values with the number of Rp methylphosphonate centers in the heptamer was found: the more Rp centers, the higher the stability of the complex. Tm values for the diastereomers with 6 all-Rp or all-Sp methylphosphonate centers were found to be 30.5 degrees and 12.5 degrees C, respectively, in 100 mM NaCl, 10 mM Na2HPO4, 1 mM EDTA, pH 7.0 with 15 microM of each oligomer. On the average, each substitution of one Rp-center to an Sp-center in the heptamer decreased the Tm by 3 degrees C. Under the same conditions, the Tm of the normal DNA heptamer with its complement was 21 degrees C. These results are consistent with the model that all-Rp methylphosphonate DNAs hybridize much more tightly to complementary normal DNA than do racemic methylphosphonate DNAs, and may therefore exhibit greater potency as antisense inhibitors. PMID:8036171

  20. AP1000{sup R} licensing and deployment in the United States

    SciTech Connect

    Jordan, R. P.; Russ, P. A.; Filiak, P. P.; Castiglione, L. L.

    2012-07-01

    In recent years, both domestic and foreign utilities have turned to the standardized Westinghouse AP1000 plant design in satisfying their near - and long-term - sustainable energy needs. As direct support to these actions, licensing the AP1000 design has played a significant role by providing one of the fundamental bases in clearing regulatory hurdles leading to the start of new plant construction. Within the U.S. alone, Westinghouse AP1000 licensing activities have reached unprecedented milestones with the approvals of both AP1000 Design Certification and Southern Company's combined construction permit and operating license (COL) application directly supporting the construction of two new nuclear plants in Georgia. Further COL application approvals are immediately pending for an additional two AP1000 plants in South Carolina. And, across the U.S. nuclear industry spectrum, there are 10 other COL applications under regulatory review representing some 16 new plants at 10 sites. In total, these actions represent the first wave of new plant licensing under the regulatory approval process since 1978. Fundamental to the Nuclear Regulatory Commission's AP1000 Design Certification is the formal recognition of the AP1000 passive safety design through regulatory acceptance rulemaking. Through recognition and deployment of the AP1000 Design Certification, the utility licensee / operator of this reactor design are now offered an opportunity to use a simplified 'one-step' combined license process, thereby managing substantial back-end construction schedule risk from regulatory and intervention delays. Application of this regulatory philosophy represents both acceptance and encouragement of standardized reactor designs like the AP1000. With the recent AP1000 Design Certification and utility COL acceptances, the fundamental licensing processes of this philosophy have successfully proven the attainment of significant milestones with the next stage licensing actions directed

  1. In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing.

    PubMed

    Li, Xiaoling; Fan, Rangrang; Tong, Aiping; Yang, Meijia; Deng, Jiaojiao; Zhou, Liangxue; Zhang, Xiaoning; Guo, Gang

    2015-11-10

    In situ gel-forming system as local drug delivery system in dermal traumas has generated a great interest. Accumulating evidence shows that antimicrobial peptides play pivotal roles in the process of wound healing. Here in this study, to explore the potential application of antimicrobial peptide in wound healing, biodegradable poly(L-lactic acid)-Pluronic L35-poly(L-lactic acid) (PLLA-L35-PLLA) was developed at first. Then based on this polymer, an injectable in situ gel-forming system composed of human antimicrobial peptides 57 (AP-57) loaded nanoparticles and thermosensitive hydrogel was prepared and applied for cutaneous wound healing. AP-57 peptides were enclosed with biocompatible nanoparticles (AP-57-NPs) with high drug loading and encapsulation efficiency. AP-57-NPs were further encapsulated in a thermosensitive hydrogel (AP-57-NPs-H) to facilitate its application in cutaneous wound repair. As a result, AP-57-NPs-H released AP-57 in an extended period and exhibited quite low cytotoxicity and high anti-oxidant activity in vitro. Moreover, AP-57-NPs-H was free-flowing liquid at room temperature, and can form non-flowing gel without any crosslink agent upon applied on the wounds. In vivo wound healing assay using full-thickness dermal defect model of SD rats indicated that AP-57-NPs-H could significantly promote wound healing. At day 14 after operation, AP-57-NPs-H treated group showed nearly complete wound closure of 96.78 ± 3.12%, whereas NS, NPs-H and AP-57-NPs group recovered by about 68.78 ± 4.93%, 81.96 ± 3.26% and 87.80 ± 4.62%, respectively. Histopathological examination suggested that AP-57-NPs-H could promote cutaneous wound healing through enhancing granulation tissue formation, increasing collagen deposition and promoting angiogenesis in the wound tissue. Therefore, AP-57-NPs-H might have potential application in wound healing.

  2. PfAP2Tel, harbouring a non-canonical DNA-binding AP2 domain, binds to Plasmodium falciparum telomeres.

    PubMed

    Sierra-Miranda, Miguel; Vembar, Shruthi S; Delgadillo, Dulce María; Ávila-López, P A; Vargas, Miguel; Hernandez-Rivas, Rosaura

    2017-04-04

    The telomeres of the malaria parasite Plasmodium falciparum are essential not only for chromosome end maintenance during blood stage development in humans but also to generate genetic diversity by facilitating homologous recombination of subtelomeric, multigene virulence families such as var and rifin. However, other than the telomerase PfTERT, proteins that act at P. falciparum telomeres are poorly characterized. To isolate components that bind to telomeres, we performed oligonucleotide pulldowns and electromobility shift assays with a telomeric DNA probe and identified a non-canonical member of the ApiAP2 family of transcription factors, PfAP2Tel (encoded by PF3D7_0622900), as a component of the P. falciparum telomere-binding protein complex. PfAP2Tel is expressed throughout the intra-erythrocytic life cycle and localizes to the nuclear periphery, co-localizing with telomeric clusters. Furthermore, EMSAs using the recombinant protein demonstrated direct binding of PfAP2Tel to telomeric repeats in vitro, while genome-wide chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) corroborated the high specificity of this protein to telomeric ends of all 14 chromosomes in vivo. Taken together, our data describe a novel function for ApiAP2 proteins at chromosome ends and open new avenues to study the molecular machinery that regulates telomere function in P. falciparum.

  3. Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha

    PubMed Central

    Tang, Mingyong; Tao, Yan-Bin

    2016-01-01

    Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha. PMID:27168978

  4. Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha.

    PubMed

    Tang, Mingyong; Tao, Yan-Bin; Xu, Zeng-Fu

    2016-01-01

    Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha.

  5. The AP-1 μ adaptin is required for KNOLLE localization at the cell plate to mediate cytokinesis in Arabidopsis.

    PubMed

    Teh, Ooi-Kock; Shimono, Yuki; Shirakawa, Makoto; Fukao, Yoichiro; Tamura, Kentaro; Shimada, Tomoo; Hara-Nishimura, Ikuko

    2013-06-01

    Formation of clathrin-coated vesicles (CCVs) requires the scaffolding adaptor protein (AP) complexes, which are conserved across all eukaryotes. The Arabidopsis genome encodes five AP complexes (AP-1 to AP-5), and each complex consists of four subunits. In this study, we characterized the poorly defined AP-1 complex by using genetics, proteomics and live cell imaging. We showed that the AP-1 µ adaptin subunit (AP1M2) was localized to the trans-Golgi network (TGN) and interacted physically with the AP-1 subunits in Arabidopsis. During treatment with brefeldin A (BFA), the functional fluorophore-tagged AP1M2 relocated to the BFA compartment. The AP1M2 loss-of-function mutant ap1m2 displayed deleterious growth defects, which were particularly evident in the compromised cytokinesis that was revealed by the presence of cell wall stubs in multinucleate cells. Immunolocalization of the cytokinesis-specific syntaxin KNOLLE (KN) in ap1m2 showed that KN was mislocalized and aggregated around the division plane, while a secretory marker targeting to the cell plate remained unaffected. Taken together, we propose that the AP-1 complex is required for cell plate-targeted trafficking of KN in dividing plant cells, and that it has a common role in mediating plant and yeast/animal cytokinesis systems which are fundamentally different.

  6. Altered retinal cell differentiation in the AP-3 delta mutant (Mocha) mouse.

    PubMed

    Baguma-Nibasheka, Mark; Kablar, Boris

    2009-11-01

    Adaptor-related protein complex 3 delta 1 (Ap3d1) encodes the delta 1 subunit of an adaptor protein regulating intracellular vesicle-mediated transport, and the Ap3d-deletion mutant (Mocha) mouse undergoes rapid photoreceptor degeneration leading to blindness soon after birth. Previous microarray analysis revealed Ap3d down-regulation in the retina of mouse embryos specifically lacking cholinergic amacrine cells as a result of the absence of skeletal musculature. To investigate the role of Ap3d in the determination of retinal cell fate, the present study examined retinal morphology in newborn Ap3d-/- mice. The Ap3d-/- retina showed a complete absence of cholinergic amacrine cells and a decrease in parvalbumin-expressing amacrine cells and syntaxin- and VC1.1-expressing amacrine precursor cells, but had a normal number of cell layers and number of cells in each layer with no detectable difference in cell proliferation or apoptosis. These findings indicate that, despite having no apparent effect on the basic spatial organization of the retina at this stage of development, Ap3d could be involved in the regulation of progenitor cell competence and the eventual ratio of resulting differentiated cells. Finding the mouse mutant which phenocopies the eye defect seen in fetuses with no striated muscle was accomplished by the Systematic Subtractive Microarray Analysis Approach (SSMAA), explained in the discussion section.

  7. Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng

    PubMed Central

    Baek, Kwang-Soo; Hong, Yong Deog; Kim, Yong; Sung, Nak Yoon; Yang, Sungjae; Lee, Kyoung Min; Park, Joo Yong; Park, Jun Seong; Rho, Ho Sik; Shin, Song Seok; Cho, Jae Youl

    2014-01-01

    Background Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. Methods The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. Results AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. Conclusion Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy. PMID:26045689

  8. The small G-protein Arf6GTP recruits the AP-2 adaptor complex to membranes.

    PubMed

    Paleotti, Olivia; Macia, Eric; Luton, Frederic; Klein, Stephanie; Partisani, Mariagrazia; Chardin, Pierre; Kirchhausen, Tom; Franco, Michel

    2005-06-03

    The small GTP-binding protein ADP-ribosylation factor 6 (Arf6) is involved in plasma membrane/endosomes trafficking. However, precisely how the activation of Arf6 regulates vesicular transport is still unclear. Here, we show that, in vitro, recombinant Arf6GTP recruits purified clathrin-adaptor complex AP-2 (but not AP-1) onto phospholipid liposomes in the absence of phosphoinositides. We also show that phosphoinositides and Arf6 tightly cooperate to translocate AP-2 to the membrane. In vivo, Arf6GTP (but not Arf6GDP) was found associated to AP-2. The expression of the GTP-locked mutant of Arf6 leads to the plasma membrane redistribution of AP-2 in Arf6GTP-enriched areas. Finally, we demonstrated that the expression of the GTP-locked mutant of Arf6 inhibits transferrin receptor internalization without affecting its recycling. Altogether, our results demonstrated that Arf6GTP interacts specifically with AP-2 and promotes its membrane recruitment. These findings strongly suggest that Arf6 plays a major role in clathrin-mediated endocytosis by directly controlling the assembly of the AP-2/clathrin coat.

  9. Multiple Bcl-2 family immunomodulators from vaccinia virus regulate MAPK/AP-1 activation.

    PubMed

    Torres, Alice A; Albarnaz, Jonas D; Bonjardim, Cláudio A; Smith, Geoffrey L

    2016-09-01

    Vaccinia virus (VACV) is a poxvirus and encodes many proteins that modify the host cell metabolism or inhibit the host response to infection. For instance, it is known that VACV infection can activate the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathway and inhibit activation of the pro-inflammatory transcription factor NF-κB. Since NF-κB and MAPK/AP-1 share common upstream activators we investigated whether six different VACV Bcl-2-like NF-κB inhibitors can also influence MAPK/AP-1 activation. Data presented show that proteins A52, B14 and K7 each contribute to AP-1 activation during VACV infection, and when expressed individually outwith infection. B14 induced the greatest stimulation of AP-1 and further investigation showed B14 activated mainly the MAPKs ERK (extracellular signal-regulated kinase) and JNK (Jun N-terminal kinase), and their substrate c-Jun (a component of AP-1). These data indicate that the same viral protein can have different effects on distinct signalling pathways, in blocking NF-κB activation whilst leading to MAPK/AP-1 activation.

  10. ERK-associated changes of AP-1 proteins during fear extinction.

    PubMed

    Guedea, Anita L; Schrick, Christina; Guzman, Yomayra F; Leaderbrand, Katie; Jovasevic, Vladimir; Corcoran, Kevin A; Tronson, Natalie C; Radulovic, Jelena

    2011-06-01

    Extensive research has unraveled the molecular basis of learning processes underlying contextual fear conditioning, but the mechanisms of fear extinction remain less known. Contextual fear extinction occurs when an aversive stimulus that initially caused fear is no longer present and depends on the activation of the extracellular signal-regulated kinase (ERK), among other molecules. Here we investigated how ERK signaling triggered by extinction affects its downstream targets belonging to the activator protein-1 (AP-1) transcription factor family. We found that extinction, when compared to conditioning of fear, markedly enhanced the interactions of active, phospho-ERK (pERK ) with c-Jun causing alterations of its phosphorylation state. The AP-1 binding of c-Jun was decreased whereas AP-1 binding of JunD, Jun dimerization protein 2 (JDP2) and ERK were significantly enhanced. The increased AP-1 binding of the inhibitory JunD and JDP2 transcription factors was paralleled by decreased levels of the AP-1 regulated proteins c-Fos and GluR2. These changes were specific for extinction and were MEK-dependent. Overall, fear extinction involves ERK/Jun interactions and a decrease of a subset of AP-1-regulated proteins that are typically required for fear conditioning. Facilitating the formation of inhibitory AP-1 complexes may thus facilitate the reduction of fear.

  11. AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.

    PubMed

    Yang, Meijia; Tang, Mei; Ma, Xianjun; Yang, Lijia; He, Jiangpeng; Peng, Xirui; Guo, Gang; Zhou, Liangxue; Luo, Na; Yuan, Zhu; Tong, Aiping

    2015-02-13

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.

  12. AP-1A controls secretory granule biogenesis and trafficking of membrane secretory granule proteins.

    PubMed

    Bonnemaison, Mathilde; Bäck, Nils; Lin, Yimo; Bonifacino, Juan S; Mains, Richard; Eipper, Betty

    2014-10-01

    The adaptor protein 1A complex (AP-1A) transports cargo between the trans-Golgi network (TGN) and endosomes. In professional secretory cells, AP-1A also retrieves material from immature secretory granules (SGs). The role of AP-1A in SG biogenesis was explored using AtT-20 corticotrope tumor cells expressing reduced levels of the AP-1A μ1A subunit. A twofold reduction in μ1A resulted in a decrease in TGN cisternae and immature SGs and the appearance of regulated secretory pathway components in non-condensing SGs. Although basal secretion of endogenous SG proteins was unaffected, secretagogue-stimulated release was halved. The reduced μ1A levels interfered with the normal trafficking of carboxypeptidase D (CPD) and peptidylglycine α-amidating monooxygenase-1 (PAM-1), integral membrane enzymes that enter immature SGs. The non-condensing SGs contained POMC products and PAM-1, but not CPD. Based on metabolic labeling and secretion experiments, the cleavage of newly synthesized PAM-1 into PHM was unaltered, but PHM basal secretion was increased in sh-μ1A PAM-1 cells. Despite lacking a canonical AP-1A binding motif, yeast two-hybrid studies demonstrated an interaction between the PAM-1 cytosolic domain and AP-1A. Coimmunoprecipitation experiments with PAM-1 mutants revealed an influence of the luminal domains of PAM-1 on this interaction. Thus, AP-1A is crucial for normal SG biogenesis, function and composition.

  13. How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.

    PubMed

    Ren, Xuefeng; Park, Sang Yoon; Bonifacino, Juan S; Hurley, James H

    2014-01-01

    The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 Å crystal structure of Nef bound to the α and σ2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef. DOI: http://dx.doi.org/10.7554/eLife.01754.001.

  14. aP2-Cre-Mediated Inactivation of Estrogen Receptor Alpha Causes Hydrometra

    PubMed Central

    Antonson, Per; Matic, Marko; Portwood, Neil; Kuiper, Raoul V.; Bryzgalova, Galyna; Gao, Hui; Windahl, Sara H.; Humire, Patricia; Ohlsson, Claes; Berggren, Per-Olof; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2014-01-01

    In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERαflox/flox mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERαflox/flox mice. Phenotypic analysis revealed that aP2-Cre/ERαflox/flox female mice were infertile. In line with this, aP2-Cre/ERαflox/flox female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERαflox/flox female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERαflox/flox mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERαflox/flox mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction. PMID:24416430

  15. Diamond monochromators for APS undulator-A beamlines

    SciTech Connect

    Blasdell, R.C.; Assoufid, L.A.; Mills, D.M.

    1995-09-01

    There has been considerable interest in the use of diamonds in high heat load monochromators (HHLMs) in the last several years. The superb thermal and mechanical properties of single crystal diamonds serve to minimize distortions caused by a given thermal load, while the low x-ray absorption cross-section reduces both the total power deposited in the crystal as well as the peak (volumetric) power density. The primary obstacle for the widespread use of diamonds at present is a lack of ready availability of perfect single crystals of the desired size and orientation. Although it is possible to obtain near-perfect natural diamonds of the size and orientation required for use on an undulator beamline, the selection process is generally one of trial and error. Near perfect synthetic diamonds can currently be obtained in the minimum necessary size (typically 4-5 mm on a side). A collaborative agreement has been made between the staff of the Advanced Photon Source (APS), the European Synchrotron Radiation Facility (ESRF), and the Super Photon Ring-8 GeV (SPring-8) to explore the use of diamonds as high heat load monochromators and is on-going. One of the avenues of research is to push for improved perfection and size of synthetic diamonds. Sumitomo Electric Corporation of Japan has agreed to work with staff from SPring-8 to grow [100] oriented perfect single crystal diamonds of 10 x 10 x 1 mm{sup 3} size by 1996/1997 (from which one could also cut pieces with the large face parallel to the (111) planes). They have taken the first step in producing an essentially perfect 4 x 4 x 1 mm{sup 3} type II diamond with less than 5 {mu}rad (1 arc second) strain (measured over the entire surface). The authors believe progress in the production of synthetic diamonds, as well as improvement in ties with suppliers of natural diamonds, should make available a relatively large number of high quality diamonds of moderate size within the next several years.

  16. Chromatic Modulator for a High-Resolution CCD or APS

    NASA Technical Reports Server (NTRS)

    Hartley, Frank; Hull, Anthony

    2008-01-01

    A chromatic modulator has been proposed to enable the separate detection of the red, green, and blue (RGB) color components of the same scene by a single charge-coupled device (CCD), active-pixel sensor (APS), or similar electronic image detector. Traditionally, the RGB color-separation problem in an electronic camera has been solved by use of either (1) fixed color filters over three separate image detectors; (2) a filter wheel that repeatedly imposes a red, then a green, then a blue filter over a single image detector; or (3) different fixed color filters over adjacent pixels. The use of separate image detectors necessitates precise registration of the detectors and the use of complicated optics; filter wheels are expensive and add considerably to the bulk of the camera; and fixed pixelated color filters reduce spatial resolution and introduce color-aliasing effects. The proposed chromatic modulator would not exhibit any of these shortcomings. The proposed chromatic modulator would be an electromechanical device fabricated by micromachining. It would include a filter having a spatially periodic pattern of RGB strips at a pitch equal to that of the pixels of the image detector. The filter would be placed in front of the image detector, supported at its periphery by a spring suspension and electrostatic comb drive. The spring suspension would bias the filter toward a middle position in which each filter strip would be registered with a row of pixels of the image detector. Hard stops would limit the excursion of the spring suspension to precisely one pixel row above and one pixel row below the middle position. In operation, the electrostatic comb drive would be actuated to repeatedly snap the filter to the upper extreme, middle, and lower extreme positions. This action would repeatedly place a succession of the differently colored filter strips in front of each pixel of the image detector. To simplify the processing, it would be desirable to encode information on

  17. Separating Non-Linear Deformation And Atmospheric Phase Screen (APS) For INSAR Time Series Analysis Using Least-Square Collocation

    NASA Astrophysics Data System (ADS)

    Liu, S.; Hanssen, R. F.; Samiei-Esfahany, S.; Hooper, A.; Van Leijen, F. J.

    2012-01-01

    We present a new method for separating ground defor- mation from atmospheric phase screen (APS) based on PSInSAR. By stochastic modeling of ground deformation and APS via their variance-covariance functions we can not only estimate the signals with the best accuracy but also assess the estimation accuracy using least-squares collocation[5]. We evaluate the APS estimated by our method and the APS obtained from a commonly used window-based filtering method [6] by comparing them to repeat-pass interferograms over ground surfaces outside the subsiding region of Mexico City. The comparison shows that our method results in a better estimation of APS than the filtering method which ignores the temporal variability of APS variance. Our method is desired when there are temporal gaps in a SAR time series. In such a case, the filtering method needs a large temporal window to suppress APS, which may lead to leakage from ground deformation to APS.

  18. 241-AP Tank Farm Construction Extent of Condition Review for Tank Integrity

    SciTech Connect

    Barnes, Travis J.; Gunter, Jason R.; Reeploeg, Gretchen E.

    2014-04-04

    This report provides the results of an extent of condition construction history review for the 241-AP tank farm. The construction history of the 241-AP tank farm has been reviewed to identify issues similar to those experienced during tank AY-102 construction. Those issues and others impacting integrity are discussed based on information found in available construction records, using tank AY-102 as the comparison benchmark. In the 241-AP tank farm, the sixth double-shell tank farm constructed, tank bottom flatness, refractory material quality, post-weld stress relieving, and primary tank bottom weld rejection were improved.

  19. Panel Discussion : Report of the APS Ad-Hoc Committee on LGBT Issues

    NASA Astrophysics Data System (ADS)

    Atherton, Tim; Barthelemy, Ramon; Garmon, Savannah; Reeves, Kyle; APS Ad-Hoc Committee on LGBT Issues Team

    Following the presentation of the findings and recommendations of the APS Ad-Hoc Committee on LGBT Issues (C-LGBT) by Committee Chair Michael Falk, a panel discussion will be held featuring several members of the committee. The discussion will focus on how APS can best ensure the recommendations of the committee are carried out in a timely fashion and other ideas on future APS efforts toward LGBT inclusion in physics. Discussion topics will also include the research and other input that shaped the committee's findings and recommendations.

  20. Baseline water quality of Long Meadow Lake, Ponds AP-9 and AP-10, and Black Dog Creek, Hennepin and Dakota counties, Minnesota

    USGS Publications Warehouse

    Payne, G.A.

    1977-01-01

    Long Meadow Lake, Black Dog Creek, and Ponds AP-9 and AP-10 which lie in an area designated for a trunk highway bridge crossing the Minnesota River, were sampled for baseline water quality prior to construction of the bridge. Data collected show that dissolved solids fluctuate seasonally. Dissolved oxygen:/ranged from less than 1 milligram per liter under an ice cover to 13-9 milligrams per liter in the September sample at site 4 in Long Meadow Lake. The phytoplankton analyses showed pulses in algae populations, blue-green algae being the dominant type in at least one sample from each of the water courses.

  1. WCPSS Advanced Placement (AP) Test Results, 2009-10. E&R Report No. 10.29

    ERIC Educational Resources Information Center

    McMillen, Brad

    2010-01-01

    Analysis of WCPSS' 2009-10 AP reports from the College Board reveal that the number and proportion of WCPSS students taking AP courses and exams continues to grow. Between 1996-97 and 2009-10, the number of students enrolled in WCPSS grew by approximately 63% and the number taking AP exams increased by 238% with a corresponding increase in exams…

  2. The Development of Multiple-Choice Items Consistent with the AP Chemistry Curriculum Framework to More Accurately Assess Deeper Understanding

    ERIC Educational Resources Information Center

    Domyancich, John M.

    2014-01-01

    Multiple-choice questions are an important part of large-scale summative assessments, such as the advanced placement (AP) chemistry exam. However, past AP chemistry exam items often lacked the ability to test conceptual understanding and higher-order cognitive skills. The redesigned AP chemistry exam shows a distinctive shift in item types toward…

  3. Advanced Placement Chemistry: Project Advance and the Advanced Placement Program: A Comparison of Students' Performance on the AP Chemistry Examination.

    ERIC Educational Resources Information Center

    Mercurio, Joseph; And Others

    1984-01-01

    Compared performance of Syracuse University Project Advance (PA) chemistry students (N=35) with advanced placement (AP) candidates on the AP chemistry examination. PA students scored slightly above the national average on the examination, and students who performed well (B or better) in AP chemistry also did well on the examination. (JN)

  4. APS-Workshop on Characterization of MMIC (Monolithic Microwave Integrated Circuit) Devices for Array Antenna

    NASA Technical Reports Server (NTRS)

    Smetana, Jerry (Editor); Mittra, Raj (Editor); Laprade, Nick; Edward, Bryan; Zaghloul, Amir

    1987-01-01

    The IEEE AP-S ADCOM is attempting to expand its educational, tutorial and information exchange activities as a further benefit to all members. To this end, ADCOM will be forming specialized workshops on topics of interest to its members. The first such workshop on Characterization and Packaging of MMIC Devices for Array Antennas was conceived. The workshop took place on June 13, 1986 as part of the 1986 International Symposium sponsored by IEEE AP-S and URSI in Philadelphia, PA, June 9-13, 1986. The workshop was formed to foster the interchange of ideas among MMIC device users and to provide a forum to collect and focus information among engineers experienced and interested in the topic. After brief presentations by the panelists and comments from attendees on several subtopics, the group was divided into working committees. Each committee evaluated and made recommendations on one of the subtopics.

  5. Determination of Heats of Fusion: Using Differential Scanning Calorimetry for the AP Chemistry Courses.

    ERIC Educational Resources Information Center

    Temme, Susan M.

    1995-01-01

    Describes an exercise designed to be used in an Advanced Placement (AP) chemistry course to accompany the study of thermodynamics. Uses Differential Scanning Calorimetry in teaching the concepts of thermochemistry and thermodynamics. (JRH)

  6. DETAIL VIEW OF AP 93W, ROOF LEVEL, PLATFORM DSOUTH, HB3, ...

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

    DETAIL VIEW OF AP 93W, ROOF LEVEL, PLATFORM D-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  7. Waste compatibility safety issues and final results for Tank 241-AP-103 grab samples

    SciTech Connect

    Nuzum, J.L.

    1997-10-02

    Three grab samples (3AP-97-2, 3AP-97-3, and 3AP-97-4) were taken from Riser 1 of Tank 241-AP-103 on August 21, 1997, and received by 222-S Laboratory on August 22, 1997. These samples were analyzed in accordance with Compatibility Grab Sampling and Analysis Plan for Fiscal Year 1997 (TSAP) (Field, 1997) and Data Quality Objectives for Tank Farms Waste and Compatibility Program (Mulkey et. al., 1995) (DQO) in support of the Waste Compatibility Program. No notifications were required based on sample results. Appearance and Sample Breakdown Attachment 1 illustrates subsamples generated in the laboratory for analyses and identifies their sources. Furthermore, this reference relates tank farm identification numbers to their corresponding 222-S Laboratory Information Management System sample numbers. Table 1 summarizes appearance information and over-the-top (OTR) dose readings performed on each sample. For each sample, two 20 ml subsamples were created for inorganic and radiochemical analyses.

  8. 76 FR 73720 - Knowledge and Abilities Catalog for Nuclear Power Plant Operators: Westinghouse AP1000...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment a draft NUREG, NUREG-2103, Revision 0, ``Knowledge and Abilities Catalog for Nuclear Power Plant Operators: Westinghouse AP1000 Pressurized-Water...

  9. BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

    PubMed

    Bukalo, Olena; Lee, Philip R; Fields, R Douglas

    2016-12-02

    Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation.

  10. Raising the Bar: Historically Disadvantaged Students Can Meet the AP Challenge.

    ERIC Educational Resources Information Center

    Oberjuerge, Mark

    1999-01-01

    Addresses the Advanced Placement (AP) U.S. government and politics course at Jordan High School in Long Beach (California), an inner city school with a diverse student population. Describes the course and discusses its success and benefits. (CMK)

  11. The prediction of AE, ap, and Dst at time lags between 0 and 30 hours

    NASA Technical Reports Server (NTRS)

    Smart, D. F.; Garrett, H. B.; Shea, M. A.

    1979-01-01

    The magnetic activity indexes AE, ap, and Dst are correlated with approximately 35,000 hours of interplanetary plasma and magnetic field measurements acquired near the Earth (assembled by NASA/NSSDC into a composite data sat). Lag times between the indexes and solar wind parameters ranged from 0 to 30 hours. Correlations at lags less than 6 hours yield results in agreement with previous studies. At greater lags, the correlation coefficients between the solar wind parameters and AE and ap approach these parameters' autocorrelation (persistence) values. For Dst the correlation with solar wind parameters is lower than that with AE and ap in the 3 to 4 hour lag range whereas the autocorrelation of Dst is significantly higher over the entire 0 to 30 hour lag range. The implications of these differences between AE, ap, and Dst are discussed in terms of persistence of solar wind structure.

  12. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    SciTech Connect

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang Karam, George

    2006-11-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 Å resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity.

  13. Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative.

    PubMed

    Nagatani, T; Yamamoto, T; Takao, K; Hashimoto, S; Kasahara, K; Sugihara, T; Ueki, S

    1991-01-01

    AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.

  14. [Obstetrical APS: Is there a place for additional treatment to aspirin-heparin combination?

    PubMed

    Mekinian, A; Kayem, G; Cohen, J; Carbillon, L; Abisror, N; Josselin-Mahr, L; Bornes, M; Fain, O

    2017-01-01

    Obstetrical APS is defined by thrombosis and/or obstetrical morbidity associated with persistent antiphospholipid antibodies. The aspirin and low molecular weighted heparin combination dramatically improved obstetrical outcome in APS patients. Several factors could be associated with obstetrical prognosis, as previous history of thrombosis, associated SLE, the presence of lupus anticoagulant and triple positivity of antiphospholipid antibodies. Obstetrical APS with isolated recurrent miscarriages is mostly associated with isolated anticardiolipids antibodies and have better obstetrical outcome. The pregnancy loss despite aspirin and heparin combination define the refractory obstetrical APS, and the prevalence could be estimated to 20-39%. Several other treatments have been used in small and open labeled studies, as steroids, intravenous immunoglobulins, plasma exchanges and hydroxychloroquine to improve the obstetrical outcome. Some other drugs as eculizumab and statins could also have physiopathological rational, but studies are necessary to define the place of these various drugs.

  15. Discharge and Corrosion Performance of AP65 Magnesium Alloy in Simulated Seawater: Effect of Temperature

    NASA Astrophysics Data System (ADS)

    Wang, Naiguang; Wang, Richu; Peng, Chaoqun; Peng, Bing; Feng, Yan; Hu, Chengwang

    2014-12-01

    The discharge and corrosion performance of AP65 magnesium alloy in simulated seawater with different temperatures is investigated by electrochemical techniques and corrosion morphology observation. The results indicate that AP65 alloy can hardly be activated at a large current density in the 0 °C simulated seawater, whereas the activation time is shortened, and the potential exhibits a significantly negative shift in the 35 °C simulated seawater. However, the increase in temperature promotes the localized corrosion and thus is detrimental to the anode efficiency of AP65 alloy. Moreover, the effect of seawater temperature and current density on the surface morphology of AP65 alloy during the discharge process is also analyzed.

  16. Network inference from AP-MS data: computational challenges and solutions.

    PubMed

    Teng, Ben; Zhao, Can; Liu, Xiaoqing; He, Zengyou

    2015-07-01

    Protein-protein interaction is of primary importance to understand protein functions. In recent years, the high-throughput AP-MS experiments have generated a large amount of bait-prey data, posing great challenges on the computational analysis of such data for inferring true interactions and protein complexes. To date, many research efforts have been devoted to developing novel computational methods to analyze these AP-MS data sets. In this article, we review and classify the key computational methods developed for the inference of protein-protein interactions and the detection of protein complexes from the AP-MS experiments. We hope that our review as well as the challenges highlighted in the article will provide valuable insights into driving future research for further advancing the state-of-the-art technologies in computational prediction, characterization and analysis of protein-protein interactions and protein complexes from the AP-MS data.

  17. Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution.

    PubMed

    Martinez, Ronny; Jakob, Felix; Tu, Ran; Siegert, Petra; Maurer, Karl-Heinz; Schwaneberg, Ulrich

    2013-03-01

    Bacillus gibsonii Alkaline Protease (BgAP) is a recently reported subtilisin protease exhibiting activity and stability properties suitable for applications in laundry and dish washing detergents. However, BgAP suffers from a significant decrease of activity at low temperatures. In order to increase BgAP activity at 15°C, a directed evolution campaign based on the SeSaM random mutagenesis method was performed. An optimized microtiter plate expression system in B. subtilis was established and classical proteolytic detection methods were adapted for high throughput screening. In parallel, the libraries were screened for increased residual proteolytic activity after incubation at 58°C. Three iterative rounds of directed BgAP evolution yielded a set of BgAP variants with increased specific activity (K(cat)) at 15°C and increased thermal resistance. Recombination of both sets of amino acid substitutions resulted finally in variant MF1 with a 1.5-fold increased specific activity (15°C) and over 100 times prolonged half-life at 60°C (224 min compared to 2 min of the WT BgAP). None of the introduced amino acid substitutions were close to the active site of BgAP. Activity-altering amino acid substitutions were from non-charged to non-charged or from sterically demanding to less demanding. Thermal stability improvements were achieved by substitutions to negatively charged amino acids in loop areas of the BgAP surface which probably fostered ionic and hydrogen bonds interactions.

  18. AP1 enhances polyomavirus DNA replication by promoting T-antigen-mediated unwinding of DNA.

    PubMed Central

    Guo, W; Tang, W J; Bu, X; Bermudez, V; Martin, M; Folk, W R

    1996-01-01

    An early step in the initiation of polyomavirus DNA replication is viral large-T-antigen-mediated unwinding of the origin. We report that components of the AP1 transcription factor, Fos and Jun, interact with T antigen in vitro to enhance unwinding of the viral origin. This provides a biochemical basis for the capacity of AP1 to activate viral DNA replication in vivo. PMID:8763994

  19. Antiphospholipid syndrome (APS) revisited: Would migraine headaches be included in future classification criteria?

    PubMed

    Noureldine, Mohammad Hassan A; Haydar, Ali A; Berjawi, Ahmad; Elnawar, Rody; Sweid, Ahmad; Khamashta, Munther A; Hughes, Graham R V; Uthman, Imad

    2016-07-16

    Headaches have been extensively reported in Antiphospholipid syndrome (APS)/Antiphospholipid antibodies (aPL)-positive patients. The aim of this study was to highlight the prevalence of headaches among APS/aPL-positive patients and discuss its association with laboratory, clinical and imaging findings. We searched the literature through Google Scholar and PubMed for publications on the epidemiology, pathogenesis, laboratory, imaging and clinical findings, and management of headaches in APS/aPL-positive patients. The following keywords were used: Antiphospholipid, Hughes syndrome, anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I, headache, migraine, tension, and cluster. All reports published between 1969 and 2015 were included. Migraine is the most commonly reported type of headache in APS/aPL-positive patients. Thrombotic and platelet dysfunction hypotheses have been studied to uncover the pathogenic role of aPL in the development of headaches. Several studies are reporting higher levels of aPL in primary and secondary APS migraineurs, but only few reached statistical significance. Migraine patients without clinical signs/symptoms of cerebral infarction rarely show positive imaging findings. Digital subtraction angiography shows promise in demonstrating small vascular lesions otherwise not detected on computed tomography, magnetic resonance imaging, or cerebral angiograms. Although it may be solitary and harmless in many cases, the deleterious effect of migraine on the quality of life of APS patients prompts rapid diagnosis and proper management. An anticoagulation trial is advisable in APS patients with migraine as many cases of severe, refractory migraine resolved with anticoagulation therapy. The profile of migraine headaches discussed in this study permits its candidacy for inclusion in future APS classification criteria.

  20. Discontinuation of Antimicrobial Prophylaxis (AP) in Children With Spina Bifida: A Case Series Analysis

    PubMed Central

    Couloures, Kevin G; Anderson, Michael; Machiorlatti, Michael; Marsenic, Olivera; Opas, Lawrence

    2016-01-01

    Background Spina bifida increases the risk for urinary tract infections (UTI). Antimicrobial prophylaxis (AP) reduces symptomatic UTI’s but selects resistant organisms. Measures to ensure regular and complete emptying of the bladder combined with treatment of constipation reduce the risk for UTI. Objectives Demonstrate that close adherence to a catheterization regimen in children with spina bifida (Selective Treatment - ST) reduces the need for antimicrobial prophylaxis. Methods Case series analysis of pediatric spina bifida clinic patients where routine antimicrobial prophylaxis was replaced by clean-catch catheterization and daily bowel regimen (ST). Retrospective chart review of 67 children (mean entry age: 24 months, median age: 4 months; 32 Males, 35 Females) enrolled between 1986 - 2004. Mean follow-up was 128.6 months (range 3 - 257 months). Asymptomatic and symptomatic UTI incidences were noted on AP and ST protocols. Creatinine clearance at study entry and follow-up was calculated by the age appropriate method. A multivariable regression model with delta Glomerular Filtration Rate (GFR) as the dependent variable, independent sample t-test and Wilcoxon rank sum were performed with SAS v. 9.2. Results The mean number of infections while on AP was 8.7 (95% CI 5.72, 11.68) and was 1.0 on ST (95% CI 0.48, 1.43). 5 infections on the AP protocol required intravenous (IV) antibiotics due to resistance to oral therapy, but none on ST. Comparing change in GFR between both protocols (AP vs. ST) found a significant difference in the change of GFR by treatment protocol. Conclusions AP did not prevent UTIs and resulted in more resistant organisms requiring IV antibiotics. Discontinuing AP allowed the return of susceptibility to oral antimicrobials and significantly improved GFR in those children who had previously been on AP. Adherence to a catheterization regimen with prompt treatment of symptomatic UTI conserved renal function and prevented selection of resistant

  1. Periodic variation in the geomagnetic activity - A study based on the Ap index

    NASA Technical Reports Server (NTRS)

    De Gonzalez, Alicia L. C.; Gonzalez, Walter D.; Dutra, Severino L. G.; Tsurutani, Bruce T.

    1993-01-01

    The monthly and daily samples of the Ap index for the interval from 1932 through 1982 were studied using the power spectrum technique. Results obtained for Bartel's period (about 27 days), the semiannual period, the dual-peak solar cycle distribution of geomagnetic storms, and certain other medium-scale periodicities are examined in detail. In addition, results on the cumulative occurrence number of storms per decade as a function of the Ap and Dst indices for the storm are presented.

  2. Status of the fluorescent screens and image processing for the APS linac

    SciTech Connect

    Berg, W.; Ko, K.

    1993-11-01

    Ten fluorescent screens and cameras determine the relative position and image profile of the beam in both the electron and positron linacs at the Advanced Photon Source (APS). The timing techniques used to capture the beam image allow direct synchronization to the electron gun trigger to minimize timing uncertainties. This paper discusses the design and status of the APS linac fluorescent screen assemblies and imaging system.

  3. Ultrasonic Inspection Results of Double Shell Tank (DST) 241-AP-108 [SEC 1 and 2

    SciTech Connect

    JENSEN, C.E.

    2000-09-11

    This document presents the results and documentation of the non-destructive ultrasonic examination (NDE) of tank 241-AP-107. An NDE contractor was retained to provide and use an ultrasonic inspection system (equipment, procedures, and inspectors) to scan a limited area of the primary tank wall, welds, and lower knuckle of double-shell tank 241-AP-107. The exam found no reportable indications of wall thinning, pits, or crack in excess of the acceptance criteria.

  4. Building a world-class A/P function: how UPMC went paperless.

    PubMed

    DeLuca, Michael; Smith, Corey

    2010-03-01

    UPMC engaged people, processes, and technology to move its A/P function from a highly manual, paper-based operation to a completely automated process. UPMC's CFO hired a chief supply chain officer to develop a strategic plan, and UPMC named a value analysis team to gain clinician buy-in. UPMC automated A/P by enabling receipt of electronic invoices. UPMC streamlined its processes for invoices.

  5. Molecular basis for association of PIPKI gamma-p90 with clathrin adaptor AP-2.

    PubMed

    Kahlfeldt, Nina; Vahedi-Faridi, Ardeschir; Koo, Seong Joo; Schäfer, Johannes G; Krainer, Georg; Keller, Sandro; Saenger, Wolfram; Krauss, Michael; Haucke, Volker

    2010-01-22

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the I gamma-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P(2) metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKI gamma-p90 associates with both the mu and beta2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKI gamma-p90 tail binds to a cognate recognition site on the sandwich subdomain of the beta2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2mu, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKI gamma-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKI gamma tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2 beta and AP-2mu. Our data also suggest that interactions between AP-2 and the tail domain of PIPKI gamma-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKI gamma-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated SV endocytosis.

  6. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease

    PubMed Central

    Tarozzi, Andrea; Bartolini, Manuela; Piazzi, Lorna; Valgimigli, Luca; Amorati, Riccardo; Bolondi, Cecilia; Djemil, Alice; Mancini, Francesca; Andrisano, Vincenza; Rampa, Angela

    2014-01-01

    The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer's disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Aβ42 self-aggregation, Aβ42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease. PMID:25505579

  7. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease.

    PubMed

    Tarozzi, Andrea; Bartolini, Manuela; Piazzi, Lorna; Valgimigli, Luca; Amorati, Riccardo; Bolondi, Cecilia; Djemil, Alice; Mancini, Francesca; Andrisano, Vincenza; Rampa, Angela

    2014-04-01

    The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer's disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Aβ 42 self-aggregation, Aβ 42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ 42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease.

  8. RbAp46/48(LIN-53) Is Required for Holocentromere Assembly in Caenorhabditis elegans.

    PubMed

    Lee, Bernard Chi Hang; Lin, Zhongyang; Yuen, Karen Wing Yee

    2016-03-01

    Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histone H3 variant, CENP-A. To maintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished. The licensing factor M18BP1(KNL-2) is known to recruit CENP-A to holocentromeres. Here, we show that RbAp46/48(LIN-53), a conserved histone chaperone, is required for CENP-A(HCP-3) localization in holocentric Caenorhabditis elegans. Indeed, RbAp46/48(LIN-53) and CENP-A(HCP-3) localizations are interdependent. RbAp46/48(LIN-53) localizes to the centromere during metaphase in a CENP-A(HCP-3)- and M18BP1(KNL-2)-dependent manner, suggesting CENP-A(HCP-3) loading may occur before anaphase. RbAp46/48(LIN-53) does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes. RbAp46/48(LIN-53) may function independently to escort CENP-A(HCP-3) for holocentromere assembly but is dispensable for other kinetochore protein recruitment. Nonetheless, depletion of RbAp46/48(LIN-53) leads to anaphase bridges and chromosome missegregation. This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres.

  9. Loss-of-normal-feedwater sensitivity studies for AP600 behavior characterization

    SciTech Connect

    Saiu, G.; Del Nero, G.; Madonna, A.; Marella, G.; Orazi, A.

    1996-09-01

    Activity concerning the development of a RELAP5/MOD3 model to simulate the Westinghouse Electric Corporation AP600 is summarized. The aim is to gain initial insight into the capability of RELAP5 to simulate the behavior of AP600 safety features. A-loss-of-normal-feedwater event is studied. Of the transients that must be investigated, this transient has been chosen to be one of the most relevant because the response of the AP600 to a loss-of-normal-feedwater event differs significantly from that of current pressurized water reactors in the extensive use of passive safety features peculiar to the AP600. Also, strong interactions among the AP600 safety systems, which should be further analyzed to permit full optimization of the system actuation logic and operation, are shown. Finally, a loss of normal feedwater without reactor scram, performed to investigate short-term plant behavior, shows that the pressure peak is affected by critical discharge flow coefficients applied to the pressurizer safety valves, while a relatively small reduction of the pressure peak is observed when both heat exchangers of the passive heat removal system are operating as opposed to the case in which only one is available. The data used for this study are derived from the Standard Safety Analysis Report configuration of the Westinghouse AP600 as of 1992.

  10. CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection

    PubMed Central

    Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L.; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

    2015-01-01

    African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity. PMID:25915900

  11. Adrenergic inducibility of AP-1 binding in the rat pineal gland depends on prior photoperiod.

    PubMed

    Guillaumond, F; Becquet, D; Bosler, O; François-Bellan, A M

    2002-10-01

    The main known function of the pineal gland in mammals is the temporal synchronization of physiological rhythms to seasonal changes of day length (photoperiod). In rat, the transcription factor activating protein-1 (AP-1) displays a circadian rhythm in its DNA binding in the pineal gland, which results from the rhythmic expression of Fra-2. We postulated that, if AP-1 is an important component of pineal gland functioning, then variations in photoperiodic conditions should lead to an adaptation of the AP-1 binding rhythm. Here we show that AP-1 binding patterns adapt to variations in lighting conditions, in the same way as the rhythm of arylalkylamine-N-acetyltransferase (AA-NAT) activity. This adaptation appeared to result from photoperiodic adaptation of the rhythmic fra-2 gene expression and was reflected by an adapted delay between the onset of night and the acrophase of the nocturnal peak. We further showed that photoperiodic adaptation of both the AP-1 binding and AA-NAT activity rhythms resulted from adapted changes in adrenergic inducibility of both variables at night onset. We finally provided evidence that AP-1 shared with the CREM gene encoding the transcriptional repressor protein inducible cAMP early repressor (ICER) the ability to be hypersensitive or subsensitive to adrenergic stimuli, depending on prior photoperiod.

  12. Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

    PubMed Central

    2010-01-01

    Background The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). Results Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders. PMID:20602773

  13. CsAP3: A Cucumber Homolog to Arabidopsis APETALA3 with Novel Characteristics

    PubMed Central

    Sun, Jin-Jing; Li, Feng; Wang, Dong-Hui; Liu, Xiao-Feng; Li, Xia; Liu, Na; Gu, Hai-Tao; Zou, Cheng; Luo, Jing-Chu; He, Chao-Xing; Huang, San-Wen; Zhang, Xiao-Lan; Xu, Zhi-Hong; Bai, Shu-Nong

    2016-01-01

    In our previous efforts to understand the regulatory mechanisms of cucumber unisexual flower development, we observed a stamen-specific down-regulation of the ethylene receptor CsETR1 in stage 6 female flowers of cucumber (Cucumis sativus L.). This down-regulation is correlated with the primordial anther-specific DNA damage that characterizes inappropriate stamen development in cucumber female flowers. To understand how CsETR1 is down regulated in the stamen, we characterized a cucumber MADS box gene homologous to Arabidopsis AP3, CsAP3. We demonstrated that CsAP3 is functionally equivalent to the Arabidopsis B-class MADS gene AP3. However, three novel characteristics of CsAP3 were found. These include firstly, binding and activating CsETR1 promoter in vitro and in vivo; secondly, containing a GV repeat in its C-terminus, which is conserved in cucurbits and required for the transcription activation; and thirdly, decreased expression as the node number increases, which is similar to that found for CsETR1. These findings revealed not only the conserved function of CsAP3 as a B-class floral identity gene, but also its unique functions in regulation of female flower development in cucumber. PMID:27540391

  14. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study.

    PubMed

    Bouvier, Sylvie; Cochery-Nouvellon, Eva; Lavigne-Lissalde, Géraldine; Mercier, Erick; Marchetti, Tess; Balducchi, Jean-Pierre; Marès, Pierre; Gris, Jean-Christophe

    2014-01-16

    The incidence of pregnancy outcomes for women with the purely obstetric form of antiphospholipid syndrome (APS) treated with prophylactic low-molecular-weight heparin (LMWH) plus low-dose aspirin (LDA) has not been documented. We observed women without a history of thrombosis who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal loss at or beyond the 10th week. We compared the frequencies of complications during new pregnancies between treated women with APS (n = 513; LMWH + LDA) and women negative for antiphospholipid antibodies as controls (n = 791; no treatment). Among APS women, prior fetal loss was a risk factor for fetal loss, preeclampsia (PE), premature birth, and the occurrence of any placenta-mediated complication. Being positive for anticardiolipin immunoglobulin M antibodies was a risk factor for any placenta-mediated complication. Among women with a history of recurrent abortion, APS women were at a higher risk than other women of PE, placenta-mediated complications, and neonatal mortality. Among women with prior fetal loss, LMWH + LDA-treated APS women had lower pregnancy loss rates but higher PE rates than other women. Improved therapies, in particular better prophylaxis of late pregnancy complications, are urgently needed for obstetric APS and should be evaluated according to the type of pregnancy loss.

  15. Retinoids interfere with the AP1 signalling pathway in human breast cancer cells.

    PubMed

    Dedieu, Stephane; Lefebvre, Philippe

    2006-06-01

    Retinoic acid and its synthetic analogs exert major effects on many biological processes including cell proliferation and differentiation and are now considered as promising pharmacological agents for prevention and treatment of various cancers. The capacity of retinoids to inhibit AP1-responsive genes seems to be the basis for the chemopreventive and chemotherapeutic effects of these agents against hyperproliferative diseases. However, the molecular basis of retinoid antiproliferative properties remains to this day largely unknown. Here, we showed that retinoids inhibit phorbol ester-induced MMP-1 and MMP-3 expression in human breast cancer cells. Transcriptional interference was observed for both retinoid agonist and antagonist treatments, revealing separated transactivation and transrepression functions of retinoids. In addition, we examined MAP kinases as potential targets of retinoid signalling in human breast cancer cells and demonstrated that retinoids repress AP1-responsive gene expression by inhibiting MKK6/p38 and mainly MEK/ERK signalling pathways. On the contrary, the JNK-dependent pathway was not identified as a molecular relay for AP1 activity and was insensitive to retinoid treatments. Finally, we established that overexpressed c-fos and c-jun partially abolished the ability of retinoids to inhibit AP1 activity, suggesting that c-jun and/or c-fos containing dimers may constitute one target of retinoids for transrepression of AP1. All together, our data help to improve our understanding of how retinoids antagonize AP1 activity and may regulate tumoral cell proliferation.

  16. CMOS-APS Detectors for Solar Physics: Lessons Learned during the SWAP Preflight Calibration

    NASA Astrophysics Data System (ADS)

    de Groof, A.; Berghmans, D.; Nicula, B.; Halain, J.-P.; Defise, J.-M.; Thibert, T.; Schühle, U.

    2008-05-01

    CMOS-APS imaging detectors open new opportunities for remote sensing in solar physics beyond what classical CCDs can provide, offering far less power consumption, simpler electronics, better radiation hardness, and the possibility of avoiding a mechanical shutter. The SWAP telescope onboard the PROBA2 technology demonstration satellite of the European Space Agency will be the first actual implementation of a CMOS-APS detector for solar physics in orbit. One of the goals of the SWAP project is precisely to acquire experience with the CMOS-APS technology in a real-live space science context. Such a precursor mission is essential in the preparation of missions such as Solar Orbiter where the extra CMOS-APS functionalities will be hard requirements. The current paper concentrates on specific CMOS-APS issues that were identified during the SWAP preflight calibration measurements. We will discuss the different readout possibilities that the CMOS-APS detector of SWAP provides and their associated pros and cons. In particular we describe the “image lag” effect, which results in a contamination of each image with a remnant of the previous image. We have characterised this effect for the specific SWAP implementation and we conclude with a strategy on how to successfully circumvent the problem and actually take benefit of it for solar monitoring.

  17. Protein phosphatase AP2C1 negatively regulates basal resistance and defense responses to Pseudomonas syringae.

    PubMed

    Shubchynskyy, Volodymyr; Boniecka, Justyna; Schweighofer, Alois; Simulis, Justinas; Kvederaviciute, Kotryna; Stumpe, Michael; Mauch, Felix; Balazadeh, Salma; Mueller-Roeber, Bernd; Boutrot, Freddy; Zipfel, Cyril; Meskiene, Irute

    2017-01-06

    Mitogen-activated protein kinases (MAPKs) mediate plant immune responses to pathogenic bacteria. However, less is known about the cell autonomous negative regulatory mechanism controlling basal plant immunity. We report the biological role of Arabidopsis thaliana MAPK phosphatase AP2C1 as a negative regulator of plant basal resistance and defense responses to Pseudomonas syringae AP2C2, a closely related MAPK phosphatase, also negatively controls plant resistance. Loss of AP2C1 leads to enhanced pathogen-induced MAPK activities, increased callose deposition in response to pathogen-associated molecular patterns or to P. syringae pv. tomato (Pto) DC3000, and enhanced resistance to bacterial infection with Pto. We also reveal the impact of AP2C1 on the global transcriptional reprogramming of transcription factors during Pto infection. Importantly, ap2c1 plants show salicylic acid-independent transcriptional reprogramming of several defense genes and enhanced ethylene production in response to Pto This study pinpoints the specificity of MAPK regulation by the different MAPK phosphatases AP2C1 and MKP1, which control the same MAPK substrates, nevertheless leading to different downstream events. We suggest that precise and specific control of defined MAPKs by MAPK phosphatases during plant challenge with pathogenic bacteria can strongly influence plant resistance.

  18. [Investigations of the left ventricular dynamics in stable-angina pectoris (AP)].

    PubMed

    Negoiţă, C I; Marcu, C; Barna, S; Ardeleanu, M

    1982-01-01

    The investigations were carried out in 78 patients with stable AP without myocardiaI infarction in their case history and in 30 controls all distributed in three series: I = 37 patients with AP and marked alterations of ventricular repolarization (ST depression ≥ 52 mm and T negative waves ≥ 2 mm); II = 41 patients with AP and normal ECG and III = 30 controls, clinically and ECG normal, of similar age with the patients in the I and II series. The investigations of the left ventricular systole periods also rendered evident in the patients with AP important alterations of ventricular repolarization (Ist series): prolonged preejection period (PEP) due to the izovolumetric contraction time (IVCT), shortening of the ejection time (LVET) and decrease of PEP/LVET ratio as well as the significant increase of S(IV)/S(I) ratio. Although slightly shortened in this series, the electromechanic systole (QS(II)) does not present statistically significant alterations, the prolonged PEP being partially counter-balaced by the shortened LVET. The most sensitive index seems to be the PEP/LVET ratio. The alterations' of the left ventricular systole periods become evident late in the course of the disease, when significant ischemic lesions are present this the method has no value in determining an early diagnosis. On the other hand this type of investigation is an useful quantitative method for estimating the functional state of the cardiac muscle in the patients with the diagnosis of AP (stage diagnosis of AP) and subsequent evolution (repeated records).

  19. CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

    PubMed

    Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

    2015-01-01

    African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

  20. Expression patterns of LmAP2L1 and LmAP2L2 encoding two-APETALA2 domain proteins during somatic embryogenesis and germination of hybrid larch (Larix x marschlinsii).

    PubMed

    Guillaumot, Damien; Lelu-Walter, Marie-Anne; Germot, Agnès; Meytraud, Fanny; Gastinel, Louis; Riou-Khamlichi, Catherine

    2008-06-16

    Two APETALA2 domain transcription factors were characterized first in angiosperms, and, recently, in several gymnosperms. These proteins are involved in several processes, from flowering to embryogenesis in Arabidopsis thaliana. We extrapolated this result to hybrid larch (Larixxmarschlinsii Coaz) resulting from a cross between European (Larix decidua) and Japanese (Larix kaempferi) larches. Somatic embryogenesis is well described and controlled for this Pinaceae. We characterized two-AP2 domain genes: LmAP2L1 and LmAP2L2. Phylogenetic analysis confirmed that LmAP2L1 and LmAP2L2 were orthologous to Norway spruce PaAP2L1 and PaAP2L2 and that L1 forms appeared to be specific to Pinaceae. RT-PCR analysis showed that larch APETALA2 was differentially expressed during late somatic embryogenesis and during the first steps of germination. Whereas LmAP2L2 was constitutively expressed during this process, LmAP2L1 expression appeared only during late somatic embryogenesis, when embryos were able to germinate. Further, LmAP2L1 appeared to be the preferentially expressed form during embryo germination. Thus, LmAP2L1 seems to be a valuable molecular marker for hybrid larch late somatic embryogenesis and could play a role during post-embryonic development.

  1. Activator protein-1 (AP-1) and response to pathogen infection in the Hong Kong oyster (Crassostrea hongkongensis).

    PubMed

    Xiang, Zhiming; Qu, Fufa; Li, Jun; Qi, Lin; Yang, Zhang; Kong, Xiaoyu; Yu, Ziniu

    2014-01-01

    Growing evidence suggests that the transcription factor activator protein-1 (AP-1), a downstream target of mitogen-activated protein kinase (MAPK) signaling, plays a major role in stimulating the synthesis of immune effector molecules during innate immune responses. We have characterized ChAP-1, an AP-1-like protein in Crassostrea hongkongensis that is a member of the AP-1 family of proteins. ChAP-1 is composed of 290 amino acid residues with a Jun and bZIP domain at the N- and C-termini, respectively, a structure similar to that of known Ap-1 proteins. ChAP-1 mRNA is expressed in several tissues analyzed, with highest expression in the mantle. Expression of ChAP-1 increases in response to Vibrio alginolyticus, Salmo haemolyticus or Salmo cerevisiae infection and, despite the location of GFP-tagged full-length ChAP-1 protein in the cytoplasm, ChAP-1 activates the transcription of an L8G5-luc reporter gene, and its over-expression can also activate the AP-1-Luc reporter gene in HEK293T cells.

  2. Insect Cell Glycosylation and Its Impact on the Functionality of a Recombinant Intracrystalline Nacre Protein, AP24.

    PubMed

    Chang, Eric P; Perovic, Iva; Rao, Ashit; Cölfen, Helmut; Evans, John Spencer

    2016-02-23

    The impacts of glycosylation on biomineralization protein function are largely unknown. This is certainly true for the mollusk shell, where glycosylated intracrystalline proteins such as AP24 (Haliotis rufescens) exist but their functions and the role of glycosylation remain elusive. To assess the effect of glycosylation on protein function, we expressed two recombinant variants of AP24: an unglycosylated bacteria-expressed version (rAP24N) and a glycosylated insect cell-expressed version (rAP24G). Our findings indicate that rAP24G is expressed as a single polypeptide containing variations in glycosylation that create microheterogeneity in rAP24G molecular masses. These post-translational modifications incorporate O- and N-glycans and anionic monosialylated and bisialylated, and monosulfated and bisulfated monosaccharides on the protein molecules. AFM and DLS experiments confirm that both rAP24N and rAP24G aggregate to form protein phases, with rAP24N exhibiting a higher degree of aggregation, compared to rAP24G. With regard to functionality, we observe that both recombinant proteins exhibit similar behavior within in vitro calcium carbonate mineralization assays and potentiometric titrations. However, rAP24G modifies crystal growth directions and is a stronger nucleation inhibitor, whereas rAP24N exhibits higher mineral phase stabilization and nanoparticle containment. We believe that the post-translational addition of anionic groups (via sialylation and sulfation), along with modifications to the protein surface topology, may explain the changes in glycosylated rAP24G aggregation and mineralization behavior, relative to rAP24N.

  3. Coincident 1.3-year Periodicities in the ap Geomagnetic Index and the Solar Wind

    NASA Technical Reports Server (NTRS)

    Paularena, K. I.; Szabo, A.; Richardson, J. D.

    1995-01-01

    Recent observations show an approximately 1.3-year period in the speed of the solar wind detected by the IMP 8 and Voyager 2 spacecraft. A similar period is also seen in the north-south (GSE) component of the magnetic field observed by IMP 8. Since both parameters are commonly used as input to models of geomagnetic activity, the 'ap' index (a measure of geomagnetic disturbance) is examined to look for this periodicity. The Lomb-Scargle periodogram method is used on the ap, plasma, and magnetic field data during the 1973-1994 time range. A dynamic FFT periodogram method is also used to analyze the ap data during this time, as well as to look for periods present between 1932 and 1972. A clear 1.3-year periodicity is present in the post-1986 data when the same period is observed in the plasma and field data. The V(2)B(zsm) and V(2)B(s) proxies for geomagnetic activity also show this periodicity. However, the southward (GSM) component of the magnetic field does not have a 1.3-year period, and neither do solar wind or ap data from 1973-1985. This demonstrates that the ap geomagnetic index can act as a proxy for solar wind periodicities at this time scale. Historic ap data are examined, and show that a similar periodicity in ap exists around 1942. Since auroral data show a 1.4-year periodicity, all these similar periods may result from a common underlying solar mechanism.

  4. Comparison of a CCD and an APS for soft X-ray diffraction

    NASA Astrophysics Data System (ADS)

    Stewart, Graeme; Bates, R.; Blue, A.; Clark, A.; Dhesi, S. S.; Maneuski, D.; Marchal, J.; Steadman, P.; Tartoni, N.; Turchetta, R.

    2011-12-01

    We compare a new CMOS Active Pixel Sensor (APS) to a Princeton Instruments PIXIS-XO: 2048B Charge Coupled Device (CCD) with soft X-rays tested in a synchrotron beam line at the Diamond Light Source (DLS). Despite CCDs being established in the field of scientific imaging, APS are an innovative technology that offers advantages over CCDs. These include faster readout, higher operational temperature, in-pixel electronics for advanced image processing and reduced manufacturing cost. The APS employed was the Vanilla sensor designed by the MI3 collaboration and funded by an RCUK Basic technology grant. This sensor has 520 x 520 square pixels, of size 25 μm on each side. The sensor can operate at a full frame readout of up to 20 Hz. The sensor had been back-thinned, to the epitaxial layer. This was the first time that a back-thinned APS had been demonstrated at a beam line at DLS. In the synchrotron experiment soft X-rays with an energy of approximately 708 eV were used to produce a diffraction pattern from a permalloy sample. The pattern was imaged at a range of integration times with both sensors. The CCD had to be operated at a temperature of -55°C whereas the Vanilla was operated over a temperature range from 20°C to -10°C. We show that the APS detector can operate with frame rates up to two hundred times faster than the CCD, without excessive degradation of image quality. The signal to noise of the APS is shown to be the same as that of the CCD at identical integration times and the response is shown to be linear, with no charge blooming effects. The experiment has allowed a direct comparison of back thinned APS and CCDs in a real soft x-ray synchrotron experiment.

  5. Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

    PubMed Central

    Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

    2015-01-01

    We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

  6. APS kinase from Arabidopsis thaliana: genomic organization, expression, and kinetic analysis of the recombinant enzyme.

    PubMed

    Lee, S; Leustek, T

    1998-06-09

    The gene encoding 5'-adenylylsulfate (APS) kinase (EC 2.7.1.25) (APK) was cloned from Arabidopsis thaliana. There is a single APK locus in A. thaliana. The coding sequence of the gene is composed of 7 exons, interrupted by 6 introns. A transcriptional initiation site was detected 120 bp 5' of the initiation codon. APK mRNA is slightly more abundant in leaves than in roots of A. thaliana and its level does not change in response to sulfur starvation. The APK protein, synthesized in vitro, is able to enter isolated intact chloroplasts. Recombinant APS kinase shows maximal activity at 10 microM APS with 5 mM ATP, but it is inhibited at APS concentrations above 10 microM. The inhibition is alleviated at higher ATP concentrations. Reciprocal plot analysis showed that the theoretical Vmax is approximately 1.2 mumol min-1 mg-1 at 25 degrees C, pH 8.0; the K(m) values are 3.6 microM APS and 1.8 mM ATP.

  7. AP-1 overexpression impairs corticosteroid inhibition of collagen production by fibroblasts isolated from asthmatic subjects.

    PubMed

    Jacques, Eric; Semlali, Abdelhabib; Boulet, Louis Philippe; Chakir, Jamila

    2010-08-01

    Asthma is characterized by airway remodeling associated with an increase in the deposition of ECM proteins such as type I collagen. These components are mainly produced by fibroblasts. Inhaled corticosteroids are considered the cornerstone of asthma therapy. Despite substantial evidence as to the anti-inflammatory action of corticosteroids, their effect on controlling ECM protein deposition in the airways is not completely understood. This study determined the effect of dexamethasone (Dex) on collagen production by bronchial fibroblasts derived from asthmatic and healthy subjects. Expression of procollagen mRNA in fibroblasts from asthmatics and normal controls was determined by quantitative PCR. Regulation of the procollagen-alpha(1)I promoter was evaluated by transient transfections. Transforming growth factor-beta (TGF-beta) protein expression was determined by ELISA. Protein expression of glucocorticoid receptor (GR) and interaction with activator protein-1 (AP-1), a collagen regulatory transcription factor, was assessed by Western blots, coimmunoprecipitations, and EMSA. AP-1 overexpression was performed by transient transfection using c-Fos/c-Jun expression plasmids. Dex significantly downregulated procollagen production and promoter activity in normal fibroblasts but had no effect on asthmatic fibroblasts. AP-1 and GR interaction increased after Dex stimulation in asthmatic fibroblasts. AP-1 overexpression in control fibroblasts abrogated collagen gene response to Dex. These results show that Dex failed to reduce collagen production in fibroblasts from asthmatic subjects. This impaired response may be related to AP-1 overexpression in these cells.

  8. Transcriptional regulation of human novel gene SPATA12 promoter by AP-1 and HSF.

    PubMed

    Li, Dan; Lin, Yiting; Liu, Zhiwen; Zhang, Yunsheng; Rong, Zhuoxian; Liu, Xuanming

    2012-12-10

    Human SPATA12 is a spermatogenesis associated gene and is supposed to function as an inhibitor during male germ cell development. SPATA12 is specifically expressed in spermatocytes, spermatids, and spermatozoa of human testis. In order to understand the regulation mechanism of SPATA12 gene expression, we identified and characterized the SPATA12 gene core promoter region and transcription factor binding sites by using reporter gene assays. AP-1 is founded to be a potential transcriptional activator of SPATA12. The promoter activity of SPATA12 was drastically declined after AP-1 binding site mutation or deletion. We also demonstrated that AP-1 combined with Smad3/4 contributes to the transcriptional regulation of SPATA12 in response to TGF-β1. The expression of SPATA12 could be induced by TGF-β1 in a dose-dependent manner, suggesting that AP-1 as an activator plays a role in the regulation of SPATA12 promoter. We have also shown that heat shock treatment could activate the expression of SPATA12 and transcription factor HSF binding sites in the SPATA12 promoter might be responsible for this heat-induction. These results suggested that AP-1 and HSF may play an important role in regulating SPATA12 promoter activity.

  9. Adaptor Protein 2 (AP-2) complex is essential for functional axogenesis in hippocampal neurons

    PubMed Central

    Kyung, Jae Won; Cho, In Ha; Lee, Sukmook; Song, Woo Keun; Ryan, Timothy A.; Hoppa, Michael B.; Kim, Sung Hyun

    2017-01-01

    The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a failure to establish action potential firing. Consequently, this impairs activity-driven Ca2+ influx and exocytosis at nerve terminals. In contrast, removal of AP-2 from older neurons does not impair axonal growth or signaling and synaptic function. Our data reveal that AP-2 has important roles in functional axogenesis by proper extension of axon as well as the formation of AIS during the early step of neurodevelopment. PMID:28139716

  10. AP-2{alpha} suppresses skeletal myoblast proliferation and represses fibroblast growth factor receptor 1 promoter activity

    SciTech Connect

    Mitchell, Darrion L.; DiMario, Joseph X.

    2010-01-15

    Skeletal muscle development is partly characterized by myoblast proliferation and subsequent differentiation into postmitotic muscle fibers. Developmental regulation of expression of the fibroblast growth factor receptor 1 (FGFR1) gene is required for normal myoblast proliferation and muscle formation. As a result, FGFR1 promoter activity is controlled by multiple transcriptional regulatory proteins during both proliferation and differentiation of myogenic cells. The transcription factor AP-2{alpha} is present in nuclei of skeletal muscle cells and suppresses myoblast proliferation in vitro. Since FGFR1 gene expression is tightly linked to myoblast proliferation versus differentiation, the FGFR1 promoter was examined for candidate AP-2{alpha} binding sites. Mutagenesis studies indicated that a candidate binding site located at - 1035 bp functioned as a repressor cis-regulatory element. Furthermore, mutation of this site alleviated AP-2{alpha}-mediated repression of FGFR1 promoter activity. Chromatin immunoprecipitation studies demonstrated that AP-2{alpha} interacted with the FGFR1 promoter in both proliferating myoblasts and differentiated myotubes. In total, these results indicate that AP-2{alpha} is a transcriptional repressor of FGFR1 gene expression during skeletal myogenesis.

  11. AP-1 transcription factor mediates VEGF-induced endothelial cell migration and proliferation.

    PubMed

    Jia, Jing; Ye, Taiyang; Cui, Pengfei; Hua, Qian; Zeng, Huiyan; Zhao, Dezheng

    2016-05-01

    VEGF, upon binding to its endothelial cell specific receptors VEGF-R1 and VEGF-R2, can induce endothelial cell migration, proliferation and angiogenesis. However, the molecular mechanism of these effects still remains unclear. In this study, we investigated whether VEGF promotes human umbilical vascular endothelial cell (HUVEC) migration and proliferation through activator protein-1 transcription factor (AP-1) family. We first showed that VEGF induces immediate-early genes AP-1 family gene expression differentially with the profound induction of JunB (both mRNA and protein) under various conditions (PBS, DMSO or control adenoviruses). The increase in AP-1 mRNA expression occurs primarily at the transcriptional level. Inhibition of AP-1 DNA binding activity by adenovirus expressing a potent dominant negative form of c-Fos (Afos) significantly attenuated VEGF-induced HUVEC migration and proliferation and cyclin D1 expression. Knockdown of JunB with adenovirus expressing JunB shRNA reduces VEGF-induced JunB expression and attenuated HUVEC migration. However the shJunB-expressing virus has no effect on VEGF-induced cyclin D1 protein expression and proliferation. These results suggest that VEGF-induced endothelial migration is mediated primarily by induction of JunB whereas the promotion of endothelial proliferation by VEGF is mediated by JunB-independent AP-1 family members.

  12. The mTOR/AP-1/VEGF signaling pathway regulates vascular endothelial cell growth.

    PubMed

    Wang, Shuo; Lu, Jiawei; You, Qingsheng; Huang, Hua; Chen, Yingying; Liu, Kun

    2016-08-16

    Vascular restenosis is a common adverse event following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The atypical Ser/Thr protein kinase mammalian target of rapamycin (mTOR) plays an important role in cell differentiation and apoptosis. Vascular restenosis caused by excessive endothelial cell proliferation can be inhibited by local application of the mTOR inhibitor rapamycin (RAPA); however, RAPA can also suppress normal vascular endothelial cell growth by blocking mTOR/VEGF signaling, although the underlying mechanism is still unclear. Here, endogenous mTOR, AP-1, and VEGF were inhibited or overexpressed to investigate the mechanism underlying the effects of RAPA. Inhibition of AP-1 or mTOR with AP-1-siRNA or RAPA treatment respectively, decreased vascular endothelial cell proliferation, upregulation of AP-1 or mTOR increased cell proliferation, and VEGF overexpression increased, while RAPA-induced mTOR inhibition decreased vascular endothelial cell proliferation, the results indicate that combining mTOR downregulation and VEGF upregulation might both inhibit restenosis and maintain normal vascular endothelial cell growth after PCI or CABG, suggest the mTOR/AP-1/VEGF pathway might play a crucial role in regulating vascular endothelial cell growth.

  13. Origination, Expansion, Evolutionary Trajectory, and Expression Bias of AP2/ERF Superfamily in Brassica napus

    PubMed Central

    Song, Xiaoming; Wang, Jinpeng; Ma, Xiao; Li, Yuxian; Lei, Tianyu; Wang, Li; Ge, Weina; Guo, Di; Wang, Zhenyi; Li, Chunjin; Zhao, Jianjun; Wang, Xiyin

    2016-01-01

    The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion. Moreover, a large-scale analysis across plants and alga suggested that this superfamily could have been originated from AP2 family, expanding to form other families (ERF, and RAV). This process was accompanied by duplicating and/or alternative deleting AP2 domain, intragenic domain sequence conversion, and/or by acquiring other domains, resulting in copy number variations, alternatively contributing to functional innovation. We found that significant positive selection occurred at certain critical nodes during the evolution of land plants, possibly responding to changing environment. In conclusion, the present research revealed origination, functional innovation, and evolutionary trajectory of the AP2/ERF superfamily, contributing to understanding their roles in plant stress tolerance. PMID:27570529

  14. Normal dendrite growth in Drosophila motor neurons requires the AP-1 transcription factor.

    PubMed

    Hartwig, Cortnie L; Worrell, Jason; Levine, Richard B; Ramaswami, Mani; Sanyal, Subhabrata

    2008-09-01

    During learning and memory formation, information flow through networks is regulated significantly through structural alterations in neurons. Dendrites, sites of signal integration, are key targets of activity-mediated modifications. Although local mechanisms of dendritic growth ensure synapse-specific changes, global mechanisms linking neural activity to nuclear gene expression may have profound influences on neural function. Fos, being an immediate-early gene, is ideally suited to be an initial transducer of neural activity, but a precise role for the AP-1 transcription factor in dendrite growth remains to be elucidated. Here we measure changes in the dendritic fields of identified Drosophila motor neurons in vivo and in primary culture to investigate the role of the immediate-early transcription factor AP-1 in regulating endogenous and activity-induced dendrite growth. Our data indicate that (a) increased neural excitability or depolarization stimulates dendrite growth, (b) AP-1 (a Fos, Jun hetero-dimer) is required for normal motor neuron dendritic growth during development and in response to activity induction, and (c) neuronal Fos protein levels are rapidly but transiently induced in motor neurons following neural activity. Taken together, these results show that AP-1 mediated transcription is important for dendrite growth, and that neural activity influences global dendritic growth through a gene-expression dependent mechanism gated by AP-1.

  15. ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells.

    PubMed

    Kang, Richard S; Fölsch, Heike

    2011-04-04

    The autosomal recessive hypercholesterolemia protein (ARH) is well known for its role in clathrin-mediated endocytosis of low-density lipoprotein receptors (LDLRs). During uptake, ARH directly binds to the FxNPxY signal in the cytoplasmic tail of LDLR. Interestingly, the same FxNPxY motif is used in basolateral exocytosis of LDLR from recycling endosomes (REs), which is facilitated by the epithelial-specific clathrin adaptor AP-1B. However, AP-1B directly interacts with neither the FxNPxY motif nor the second more distally located YxxØ sorting motif of LDLR. Here, we show that ARH colocalizes and cooperates with AP-1B in REs. Knockdown of ARH in polarized epithelial cells leads to specific apical missorting of truncated LDLR, which encodes only the FxNPxY motif (LDLR-CT27). Moreover, a mutation in ARH designed to disrupt the interaction of ARH with AP-1B specifically abrogates exocytosis of LDLR-CT27. We conclude that in addition to its role in endocytosis, ARH cooperates with AP-1B in basolateral exocytosis of LDLR from REs.

  16. Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated by the AP-4 Complex

    SciTech Connect

    Burgos, Patricia V.; Mardones, Gonzalo A.; Rojas, Adriana L.; daSilva, Luis L.P.; Prabhu, Yogikala; Hurley, James H.; Bonifacino, Juan S.

    2010-08-12

    Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the {micro}4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on 4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances {gamma}-secretase-catalyzed cleavage of APP to the pathogenic amyloid-{beta} peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.

  17. Assimilation and implications of AE-9/AP-9 in the design process of JPL missions

    NASA Astrophysics Data System (ADS)

    de Soria-Santacruz Pich, M.; Jun, I.

    2015-12-01

    The NASA AE-8/AP-8 has been the standard geospace environment specification for decades. This model describes the energetic particle environment around the Earth and is currently the default model used in the design of space missions at the Jet Propulsion Laboratory (JPL). Moreover, the model plays a critical role in the determination of the shielding and survivability of the satellites orbiting our planet. A recent update supported by the Air Force Research Laboratory (AFRL) and the National Reconnaissance Office (NRO), the AE-9/AP-9 model, was released in September 2012 and included many improvements like increased spatial resolution and the specification of the uncertainty due to instrument errors or space weather variability. A current effort at JPL is in place with the objective of making a decision within the Laboratory on the transition from AE-8/AP-8 to the new AE-9/AP-9. In this study we present the results of this effort, which involves the comparison between both versions of the model for different satellite orbits, the comparison between AE-9/AP-9 and in-situ satellite data from the Van Allen Probes and the OSTM/Jason 2 satellite, and the implications of adopting the new model for spacecraft design in terms of survivability, shielding, single event effects, and spacecraft charging.

  18. Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

    PubMed Central

    Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

    2016-01-01

    Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

  19. Accessing, Mining, and Archiving an On-line Database -- The APS Catalog of the POSS I

    NASA Astrophysics Data System (ADS)

    Humphreys, R. M.; Cabanela, J. E.; Kriessler, J.

    2000-12-01

    The APS Catalog of the POSS I is an on-line database of over 100 million stars and galaxies (http://aps.umn.edu). A unique subset of this database with over 218,000 galaxies within 30 degrees of the North Galactic Pole, the MAPS-NGP, is now available at our web site. This diameter--selected catalog (>= 10 arcsec) is the deepest galaxy catalog constructed over such a large area of the sky (3000 sq. degrees). The MAPS-NGP includes many additional parameters for the galaxy images not available in the APS Catalog. Working with members of our computer science department, we have developed a morphological classifier for galaxies that divides our galaxy type into three classes -- early, intermediate, and late. We have applied data mining techniques to identify the most useful image parameters for input into a neural network and decision--tree based classifier pipeline. We are also archiving the APS Catalog for distribution to astronomical data centers including NASA's ADC and SIMBAD at CDS. The extragalactic subset will be integrated into the NASA/IPAC extragalactic database(NED). The MAPS-NGP has already been provided to NED. The APS is supported by NASA's Applied Information Systems Research Program.

  20. Functional interaction between the glucocorticoid receptor and GANP/MCM3AP

    SciTech Connect

    Osman, Waffa; Laine, Sanna; Zilliacus, Johanna . E-mail: johanna.zilliacus@mednut.ki.se

    2006-10-06

    Glucocorticoids are widely used to treat inflammatory diseases but have a number of side effects that partly are connected to inhibition of cell proliferation. Glucocorticoids mediated their action by binding to the glucocorticoid receptor. In the present study, we have identified by two-hybrid screens the germinal center-associated protein (GANP) and MCM3-associated protein (MCM3AP), a splicing variant of GANP, as glucocorticoid receptor interacting proteins. GANP and MCM3AP can bind to the MCM3 protein involved in initiation of DNA replication. Glutathione-S-transferase-pull-down and co-immunoprecipitation assays showed that the C-terminal domain of GANP, encompassing MCM3AP, interacts with the ligand-binding domain of the glucocorticoid receptor. Characterization of the intracellular localization of GANP revealed that GANP is shuttling between the nucleus and the cytoplasm. Furthermore, we show that glucocorticoids are unable to inhibit DNA replication in HeLa cells overexpressing MCM3AP suggesting a role for both glucocorticoid receptor and GANP/MCM3AP in regulating cell proliferation.

  1. HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

    PubMed

    Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

    2015-10-23

    The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat.

  2. A dual AP-1 and SMAD decoy ODN suppresses tissue fibrosis and scarring in mice.

    PubMed

    Yuan, Hong-Feng; Huang, Hong; Li, Xiang-Yun; Guo, Wei; Xing, Wei; Sun, Zhi-Ya; Liang, Hua-Ping; Yu, Jian; Chen, Dong-Feng; Wang, Zheng-Guo; Hao, Jin; Xu, Xiang

    2013-04-01

    The transforming growth factor-β (TGF-β) signaling pathway promotes tissue fibrosis and scarring through SMAD (small mothers against decapentaplegic)-dependent and SMAD-independent mechanisms. However, inhibition of SMAD-mediated signal transduction alone induces an excessive inflammatory response that impairs the antifibrotic effects of TGF-β inhibitors. In this study, we designed and characterized a dual-functional transcription activator protein 1 (AP-1) and SMAD decoy oligodeoxynucleotide, antifibrosis oligodeoxynucleotide 4 (AFODN4) in vitro and in vivo. AFODN4 binds directly to recombinant AP-1 and SMAD with high affinity. AFODN4 significantly inhibited the DNA-binding and transcriptional activities of both AP-1 and SMAD, as well as the production of fibrotic mediators stimulated by TGF-β1 or TGF-β2 in L929 murine fibroblasts. Local administration of AFODN4 significantly inhibited fibrosis associated with acute dermal wounds in mice. Intriguingly, AFODN4 inhibited AP-1-mediated production of proinflammatory mediators, which can be caused by blockage of SMAD alone in vitro and in vivo. Collectively, these findings suggest that dual inhibition of SMAD and AP-1 signaling by AFODN4 is a useful strategy for the development of new antifibrotic agents.

  3. Ectopic Expression of Transcription Factor AP-2δ in Developing Retina: Effect on PSA-NCAM and Axon Routing

    PubMed Central

    Li, Xiaodong; Monckton, Elizabeth A.; Godbout, Roseline

    2015-01-01

    Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the AP-2δ (TFAP2D) transcription factor is expressed in one-third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as GAP43 and PSA-NCAM demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with Endo-N, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina. PMID:24188130

  4. Ectopic expression of transcription factor AP-2δ in developing retina: effect on PSA-NCAM and axon routing.

    PubMed

    Li, Xiaodong; Monckton, Elizabeth A; Godbout, Roseline

    2014-04-01

    Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the activator protein 2 (AP-2)δ (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as growth-associated protein 43 and polysialic acid-neural cell adhesion molecule (PSA-NCAM) demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with endoneuraminidase, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina.

  5. AP-1 is involved in ICOS gene expression downstream of TCR/CD28 and cytokine receptor signaling.

    PubMed

    Watanabe, Masashi; Nakajima, Shinsuke; Ohnuki, Kazunobu; Ogawa, Shuhei; Yamashita, Masakatsu; Nakayama, Toshinori; Murakami, Yasufumi; Tanabe, Kazunari; Abe, Ryo

    2012-07-01

    It has been proposed that sustained ICOS expression in chronic inflammatory immune conditions, such as autoimmunity and allergy, contributes to symptom exacerbation. Therefore modulation of ICOS gene expression could be a potential therapeutic strategy for such immune diseases. However, the precise molecular mechanisms controlling ICOS gene expression remain poorly understood. In this study, we explored transcription factors involving in ICOS gene expression and examined their roles in a physiological situation. Microarray analysis revealed that one AP-1 molecule, Fos-related antigen-2 (Fra2), was highly correlated with ICOS expression. Ectopic expression of Fra2 and other AP-1 molecules upregulated ICOS expression on T cells. We identified an AP-1-responsive site (AP1-RE) within the ICOS promoter region and demonstrated AP-1 actually binds to AP1-RE upon TCR/CD28 stimulation. Meanwhile, we found several cytokines could upregulate ICOS expression on both naïve and effector T cells in a manner independent of TCR/CD28 stimulation. These cytokine stimuli induced AP-1 binding to AP1-RE. Together, our results indicate AP-1 transcription factors are involved in ICOS gene expression downstream of both TCR/CD28 signaling and cytokine receptor signaling, and suggest AP-1 activation via cytokine receptor signaling may be one of the mechanisms maintaining high level ICOS expression in chronic inflammatory immune responses.

  6. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

    PubMed

    Gerő, Domokos; Torregrossa, Roberta; Perry, Alexis; Waters, Alicia; Le-Trionnaire, Sophie; Whatmore, Jacqueline L; Wood, Mark; Whiteman, Matthew

    2016-11-01

    The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications.

  7. Acerca del moho

    EPA Pesticide Factsheets

    El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

  8. Low concentrations of copper in drinking water increase AP-1 binding in the brain.

    PubMed

    Lung, Shyang; Li, Huihui; Bondy, Stephen C; Campbell, Arezoo

    2015-12-01

    Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson's, Menkes', Alzheimer's, and Parkinson's diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-κB, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding.

  9. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome?

    PubMed

    Mekinian, Arsene; Costedoat-Chalumeau, Nathalie; Masseau, Agathe; Tincani, Angela; De Caroli, Sara; Alijotas-Reig, Jaume; Ruffatti, Amelia; Ambrozic, Ales; Botta, Angela; Le Guern, Véronique; Fritsch-Stork, Ruth; Nicaise-Roland, Pascale; Carbonne, Bruno; Carbillon, Lionel; Fain, Olivier

    2015-01-01

    The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.

  10. Report on the value engineering workshop on APS beamline front ends

    SciTech Connect

    Kuzay, T.

    1993-01-01

    A formal value engineering evaluation process was developed to address the front end components of the beamlines for the Advanced Photon Source (APS). This process (described in Section 2) involved an information phase, a creative phase, a judgment phase, a development phase, and a recommendation phase. Technical experts from other national laboratories and industry were invited to a two-day Value Engineering Workshop on November 5-6, 1992. The results of this Workshop are described in Section 4. Following the Workshop, various actions by the APS staff led to the redesign of the front end components, which are presented in Sections 5 and 6. The cost benefit analysis is presented in Section 7. It is important of realize that an added benefit of the Workshop was to obtain numerous design evaluations and enhancements of the front end components by experts in the field. As the design work proceeds to Title II completion, the APS staff is including many of these suggestions.

  11. AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis.

    PubMed

    Delevoye, Cédric; Hurbain, Ilse; Tenza, Danièle; Sibarita, Jean-Baptiste; Uzan-Gafsou, Stéphanie; Ohno, Hiroshi; Geerts, Willie J C; Verkleij, Arie J; Salamero, Jean; Marks, Michael S; Raposo, Graça

    2009-10-19

    Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type-specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1- and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type-specific positioning of endosomes that facilitate endosome-LRO contacts and are required for organelle maturation.

  12. AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis

    PubMed Central

    Delevoye, Cédric; Hurbain, Ilse; Tenza, Danièle; Sibarita, Jean-Baptiste; Uzan-Gafsou, Stéphanie; Ohno, Hiroshi; Geerts, Willie J.C.; Verkleij, Arie J.; Salamero, Jean; Marks, Michael S.

    2009-01-01

    Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type–specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1– and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type–specific positioning of endosomes that facilitate endosome–LRO contacts and are required for organelle maturation. PMID:19841138

  13. AP-1/σ1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory

    PubMed Central

    Glyvuk, Nataliya; Tsytsyura, Yaroslav; Geumann, Constanze; D'Hooge, Rudi; Hüve, Jana; Kratzke, Manuel; Baltes, Jennifer; Böning, Daniel; Klingauf, Jürgen; Schu, Peter

    2010-01-01

    Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1–σ1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1–σ1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three σ1 subunit isoforms: A, B and C. The expressions of σ1A and σ1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from σ1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The σ1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. PMID:20203623

  14. Genome-scale functional profiling of the mammalian AP-1 signaling pathway

    PubMed Central

    Chanda, Sumit K.; White, Suhaila; Orth, Anthony P.; Reisdorph, Richard; Miraglia, Loren; Thomas, Russell S.; DeJesus, Paul; Mason, Daniel E.; Huang, Qihong; Vega, Raquel; Yu, De-Hua; Nelson, Christian G.; Smith, Brendan M.; Terry, Robert; Linford, Alicia S.; Yu, Yang; Chirn, Gung-wei; Song, Chuanzheng; Labow, Mark A.; Cohen, Dalia; King, Frederick J.; Peters, Eric C.; Schultz, Peter G.; Vogt, Peter K.; Hogenesch, John B.; Caldwell, Jeremy S.

    2003-01-01

    Large-scale functional genomics approaches are fundamental to the characterization of mammalian transcriptomes annotated by genome sequencing projects. Although current high-throughput strategies systematically survey either transcriptional or biochemical networks, analogous genome-scale investigations that analyze gene function in mammalian cells have yet to be fully realized. Through transient overexpression analysis, we describe the parallel interrogation of ≈20,000 sequence annotated genes in cancer-related signaling pathways. For experimental validation of these genome data, we apply an integrative strategy to characterize previously unreported effectors of activator protein-1 (AP-1) mediated growth and mitogenic response pathways. These studies identify the ADP-ribosylation factor GTPase-activating protein Centaurin α1 and a Tudor domain-containing hypothetical protein as putative AP-1 regulatory oncogenes. These results provide insight into the composition of the AP-1 signaling machinery and validate this approach as a tractable platform for genome-wide functional analysis. PMID:14514886

  15. LaAP2L1, a heterosis-associated AP2/EREBP transcription factor of Larix, increases organ size and final biomass by affecting cell proliferation in Arabidopsis.

    PubMed

    Li, Ai; Zhou, Yanan; Jin, Chuan; Song, Wenqin; Chen, Chengbin; Wang, Chunguo

    2013-11-01

    In Larix and in some crops, heterosis is prevalent and has been widely used in breeding to produce excellent varieties. However, the molecular basis of heterosis in Larix remains ambiguous. LaAP2L1, a member of the AP2/EREBP transcription factor family, has been suggested to be involved in heterosis in Larix hybrids. Here, the function and regulation of LaAP2L1 were further explored. Overexpression of LaAP2L1 led to markedly enlarged organs and heterosis-like traits in Arabidopsis. Fresh weight of leaves was almost twice as great as in vector controls. Likewise, seed yield of 35S::LaAP2L1 individual plants was >200% greater than that of control plants. The enlarged organs and heterosis-like traits displayed by 35S::LaAP2L1 plants were mainly due to enhanced cell proliferation and prolonged growth duration. At the molecular level, LaAP2L1 upregulated the expression of ANT, EBP1, and CycD3;1 and inhibited the expression of ARGOS in 35S::LaAP2L1 plants, suggesting an important molecular role of LaAP2L1 in regulating plant organ development. These findings provide new insights into the formation of heterosis in woody plants and suggest that LaAP2L1 has potential applications in breeding high-yielding crops and energy plants. In addition, 50 AP2/EREBP transcription factors, including LaAP2L1, in Larix were identified by transcriptome sequencing, and phylogenetic analysis was conducted. This provided information that will be important in further revealing the functions of these transcription factors.

  16. Aps and Tep Chemical Characterization: Link Between The Dom and Pom Pools

    NASA Astrophysics Data System (ADS)

    Gogou, A.; Repeta, D. J.

    The ocean inventory of dissolved organic carbon (DOC) is approximately 750 GT, comprising one of the Earth's largest carbon reservoirs on Earth. Despite its potential significance, the mechanisms that lead to DOM production and to spatial and temporal variations of DOM concentration in the world ocean are poorly understood. Chemical characterization studies show that up to 50% of HMW DOM is a structurally well-defined class of acylated polysaccharides (APS), which exhibits novel molecular-level characteris tics. Although APS synthesis occurs in the euphotic zone, a large fraction of the marine inventory of APS (appr. 10-30 GT C), resides in the deep ocean, and is approximately equal in mass to the total marine inventory of particulate organic carbon. While radiocarbon dating of deep sea DOC yields very old apparent ages (4000-6000 ybp), radiocarbon measurements made by our group on individual APS sugars shows that APS in the deep ocean has a radiocarbon value of +56 per mil, equivalent to surface water POC and DIC. This is the first clear evidence for the presence of "young" DOC in the deep ocean. One mechanism that could be important for the rapid removal of APS from surface seawater is physical removal by macroaggregates. To investigate the significance of this mechanism, we studied the chemical composition of surface-active POM (TEP) produced naturally on surface waters and in laboratory experiments, after bubbling of HMW DOM isolated from algal cultures. 1H-NMR spectral properties and molecular-level distribution of neutral sugars in natural and artificially produced TEP closely resembled those observed for cultured and oceanic HMW DOM, while they are significantly different from those of suspended particulate matter in the ocean (Gogou and Repeta, 2000). The results of these experiments provide evidence that POM with similar chemical characteristics to HMW DOM can be produced from algal-derived DOM in the surface ocean.

  17. Arsenite suppression of involucrin transcription through AP1 promoter sites in cultured human keratinocytes

    SciTech Connect

    Sinitsyna, Nadezda N.; Reznikova, Tatiana V.; Qin Qin; Song, Hyukhwan; Phillips, Marjorie A.; Rice, Robert H.

    2010-03-15

    While preserving keratinocyte proliferative ability, arsenite suppresses cellular differentiation markers by preventing utilization of AP1 transcriptional response elements. In present experiments, arsenite had a dramatic effect in electrophoretic mobility supershift analysis of proteins binding to an involucrin promoter AP1 response element. Without arsenite treatment, binding of JunB and Fra1 was readily detected in nuclear extracts from preconfluent cultures and was not detected a week after confluence, while c-Fos was detected only after confluence. By contrast, band shift of nuclear extracts from arsenite treated cultures showed only JunB and Fra1 binding in postconfluent as well as preconfluent cultures. Immunoblotting of cell extracts showed that arsenite treatment prevented the loss of Fra1 and the increase in c-Fos proteins that occurred after confluence in untreated cultures. Chromatin immunoprecipitation assays demonstrated substantial reduction of c-Fos and acetylated histone H3 at the proximal and distal AP1 response elements in the involucrin promoter and of coactivator p300 at the proximal element. Alteration of AP1 transcription factors was also examined in response to treatment with four metal containing compounds (chromate, vanadate, hemin, divalent cadmium) that also suppress involucrin transcription. These agents all influenced transcription at AP1 elements in a transcriptional reporter assay, but exhibited less effect than arsenite on binding activity assessed by mobility shift and chromatin immunoprecipitation and displayed variable effects on AP1 protein levels. These findings help trace a mechanism by which transcriptional effects of arsenite become manifest and help rationalize the unique action of arsenite, compared to the other agents, to preserve proliferative ability.

  18. The Adaptor Complex AP-4 Regulates Vacuolar Protein Sorting at the trans-Golgi Network by Interacting with VACUOLAR SORTING RECEPTOR1.

    PubMed

    Fuji, Kentaro; Shirakawa, Makoto; Shimono, Yuki; Kunieda, Tadashi; Fukao, Yoichiro; Koumoto, Yasuko; Takahashi, Hideyuki; Hara-Nishimura, Ikuko; Shimada, Tomoo

    2016-01-01

    Adaptor protein (AP) complexes play critical roles in protein sorting among different post-Golgi pathways by recognizing specific cargo protein motifs. Among the five AP complexes (AP-1-AP-5) in plants, AP-4 is one of the most poorly understood; the AP-4 components, AP-4 cargo motifs, and AP-4 functional mechanism are not known. Here, we identify the AP-4 components and show that the AP-4 complex regulates receptor-mediated vacuolar protein sorting by recognizing VACUOLAR SORTING RECEPTOR1 (VSR1), which was originally identified as a sorting receptor for seed storage proteins to target protein storage vacuoles in Arabidopsis (Arabidopsis thaliana). From the vacuolar sorting mutant library GREEN FLUORESCENT SEED (GFS), we isolated three gfs mutants that accumulate abnormally high levels of VSR1 in seeds and designated them as gfs4, gfs5, and gfs6. Their responsible genes encode three (AP4B, AP4M, and AP4S) of the four subunits of the AP-4 complex, respectively, and an Arabidopsis mutant (ap4e) lacking the fourth subunit, AP4E, also had the same phenotype. Mass spectrometry demonstrated that these four proteins form a complex in vivo. The four mutants showed defects in the vacuolar sorting of the major storage protein 12S globulins, indicating a role for the AP-4 complex in vacuolar protein transport. AP4M bound to the tyrosine-based motif of VSR1. AP4M localized at the trans-Golgi network (TGN) subdomain that is distinct from the AP-1-localized TGN subdomain. This study provides a novel function for the AP-4 complex in VSR1-mediated vacuolar protein sorting at the specialized domain of the TGN.

  19. An Analysis of the Relationship between School-Level AP® Professional Development Activity and Subsequent Student AP Performance. Research Report No. 2012-8

    ERIC Educational Resources Information Center

    Laitusis, Vytas

    2012-01-01

    The overarching purpose behind this evaluation was to gauge the impact of AP professional development (PD) on AP student outcomes in a state with a significant rate of PD implementation. The evaluation attempted to predict the level of student AP performance by the number of AP professional development events attended by teachers in that school in…

  20. Characterisation of the nucleic acid binding features of the PRRSV 7ap and its ability to induce antinuclear antibodies.

    PubMed

    Olasz, Ferenc; Dénes, Béla; Bálint, Ádám; Magyar, Tibor; Belák, Sándor; Zádori, Zoltán

    2017-03-01

    A short alternative open reading frame named ORF7a has recently been discovered within the nucleocapsid gene of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. Proteins (7ap) translated from the ORF7a of two divergent strains - a type I and a type II - are able to completely reduce the motility of nucleic acids at relatively high molar charge ratios in gel retardation assays indicating strong dsDNA- and ssRNA-binding capability. Conserved RNA- and DNA-binding properties suggest that nucleic acid binding is a functional property of the divergent 7aps, and not an arbitrary consequence of their net positive charge. Sera from Hu7ap-immunised pigs and mice did not react with Hu7ap or Hu7ap-GFP; however, antinuclear antibodies were detected in the sera of the immunised animals, suggesting an ability of Hu7ap to interact with or mimic autoantigenic macromolecules.

  1. A method of semi-quantifying β-AP in brain PET-CT 11C-PiB images.

    PubMed

    Jiang, Jiehui; Lin, Xiaoman; Wen, Junlin; Huang, Zhemin; Yan, Zhuangzhi

    2014-01-01

    Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-β peptide, β-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi-quantify β-AP. This paper proposes such a standardized value: SVβ-AP. This standardized value measures the mean ratio between the dimension of β-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVβ-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVβ-AP. The experiment results showed that it is technically feasible.

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

    PubMed

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

    2017-01-01

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

  3. The 7BM beamline at the APS: a facility for time-resolved fluid dynamics measurements

    PubMed Central

    Kastengren, Alan; Powell, Christopher F.; Arms, Dohn; Dufresne, Eric M.; Gibson, Harold; Wang, Jin

    2012-01-01

    In recent years, X-ray radiography has been used to probe the internal structure of dense sprays with microsecond time resolution and a spatial resolution of 15 µm even in high-pressure environments. Recently, the 7BM beamline at the Advanced Photon Source (APS) has been commissioned to focus on the needs of X-ray spray radiography measurements. The spatial resolution and X-ray intensity at this beamline represent a significant improvement over previous time-resolved X-ray radiography measurements at the APS. PMID:22713903

  4. A Novel Sequence in AP180 and CALM Promotes Efficient Clathrin Binding and Assembly

    PubMed Central

    Moshkanbaryans, Lia; Xue, Jing; Wark, Jesse Ray; Robinson, Phillip James

    2016-01-01

    The clathrin heavy chain N-terminal domain interacts with endocytic adapter proteins via clathrin binding motifs to assemble clathrin triskelia into cages. However, the precise mechanism of clathrin assembly is not yet known. Clathrin assembly protein AP180 has more clathrin binding motifs than any other endocytic protein and has a major role in the assembly of the clathrin coat during synaptic vesicle biogenesis. We now demonstrate that some of the previously identified binding motifs in AP180 may be non-functional and that a non-conventional clathrin binding sequence has a major influence on AP180 function. The related protein, clathrin assembly lymphoid myeloid leukemia protein (CALM), has fewer clathrin binding motifs and functions ubiquitously in clathrin-mediated endocytosis. The C-terminal ~16 kDa sub-domain in AP180, which has relatively high similarity with CALM, was shown in earlier work to have an unexplained role in clathrin binding. We identified the specific sequences in this sub-domain that bind to clathrin. Evidence for a role for these sequences in promoting clathrin binding was examined using in vitro and ex vivo experiments that compared the clathrin binding ability of site mutants with the wild type sequence. A sequence conserved in both AP180 and CALM (LDSSLA[S/N]LVGNLGI) was found to be the major interaction site and mutation caused a deficit in clathrin assembly, which is the first example of a mutation having this effect. In contrast, single or double mutation of DL(L/F) motifs in full length AP180 had no significant effect on clathrin binding, despite higher clathrin affinity for isolated peptides containing these motifs. We conclude that the novel clathrin interaction sites identified here in CALM and AP180 have a major role in how these proteins interface with clathrin. This work advances the case that AP180 and CALM are required to use a combination of standard clathrin N-terminal domain binding motifs and the sequence identified here

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

    PubMed Central

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

    2017-01-01

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

  6. Tank 241-AP-103 08/1999 Compatibility Grab Samples and Analytical Results for the Final Report

    SciTech Connect

    BELL, K.E.

    1999-12-09

    This document is the format IV, final report for the tank 241-AP-103 (AP-103) grab samples taken in August 1999 to address waste compatibility concerns. Chemical, radiochemical, and physical analyses on the tank AP-103 samples were performed as directed in ''Compatibility Grub Sampling and Analysis Plan for Fiscal Year 1999'' (Sasaki 1999a). Any deviations from the instructions provided in the tank sampling and analysis plan (TSAP) were discussed in this narrative. No notification limits were exceeded.

  7. Molecular characterization of a variant of Bacillus anthracis-specific phage AP50 with improved bacteriolytic activity.

    PubMed

    Sozhamannan, Shanmuga; McKinstry, Michael; Lentz, Shannon M; Jalasvuori, Matti; McAfee, Farrell; Smith, Angela; Dabbs, Jason; Ackermann, Hans-W; Bamford, Jaana K H; Mateczun, Alfred; Read, Timothy D

    2008-11-01

    The genome sequence of a Bacillus anthracis-specific clear plaque mutant phage, AP50c, contains 31 open reading frames spanning 14,398 bp, has two mutations compared to wild-type AP50t, and has a colinear genome architecture highly similar to that of gram-positive Tectiviridae phages. Spontaneous AP50c-resistant B. anthracis mutants exhibit a mucoid colony phenotype.

  8. Genome-wide investigation and expression analysis of AP2-ERF gene family in salt tolerant common bean

    PubMed Central

    Kavas, Musa; Kizildogan, Aslihan; Gökdemir, Gökhan; Baloglu, Mehmet Cengiz

    2015-01-01

    Apetala2-ethylene-responsive element binding factor (AP2-ERF) superfamily with common AP2-DNA binding domain have developmentally and physiologically important roles in plants. Since common bean genome project has been completed recently, it is possible to identify all of the AP2-ERF genes in the common bean genome. In this study, a comprehensive genome-wide in silico analysis identified 180 AP2-ERF superfamily genes in common bean (Phaseolus vulgaris). Based on the amino acid alignment and phylogenetic analyses, superfamily members were classified into four subfamilies: DREB (54), ERF (95), AP2 (27) and RAV (3), as well as one soloist. The physical and chemical characteristics of amino acids, interaction between AP2-ERF proteins, cis elements of promoter region of AP2-ERF genes and phylogenetic trees were predicted and analyzed. Additionally, expression levels of AP2-ERF genes were evaluated by in silico and qRT-PCR analyses. In silico micro-RNA target transcript analyses identified nearly all PvAP2-ERF genes as targets of by 44 different plant species' miRNAs were identified in this study. The most abundant target genes were PvAP2/ERF-20-25-62-78-113-173. miR156, miR172 and miR838 were the most important miRNAs found in targeting and BLAST analyses. Interactome analysis revealed that the transcription factor PvAP2-ERF78, an ortholog of Arabidopsis At2G28550, was potentially interacted with at least 15 proteins, indicating that it was very important in transcriptional regulation. Here we present the first study to identify and characterize the AP2-ERF transcription factors in common bean using whole-genome analysis, and the findings may serve as a references for future functional research on the transcription factors in common bean. PMID:27152109

  9. Supplementation of 2-Ap, Zn and La Improves 2-Acetyl-1-Pyrroline Concentrations in Detached Aromatic Rice Panicles In Vitro.

    PubMed

    Mo, Zhaowen; Huang, Jinxia; Xiao, Di; Ashraf, Umair; Duan, Meiyang; Pan, Shenggang; Tian, Hua; Xiao, Lizhong; Zhong, Keyou; Tang, Xiangru

    2016-01-01

    Aromatic rice is highly prized by consumers worldwide due to its special aromatic character. 2-acetyl-1-pyrroline (2-AP) is considered to be the single most important volatile compound responsible for aroma in aromatic rice. The present study demonstrated the effects of 2-AP, zinc (Zn) and lanthanum (La) on the 2-AP concentration of detached aromatic rice panicles in vitro. Detached panicles from three well-known aromatic cultivars, Guixiangzhan, Pin14, and Pin 15, were cultured separately in basic culture medium supplemented with 2-AP, Zn and La, and 2-AP concentrations were assessed at 7 and 14 days after culture (DAC). The results show that supplementation of 2-AP, Zn and La in the basic culture medium significantly increases the accumulation of proline. 2-AP concentration and the activity of proline dehydrogenase (ProDH) were also increased in rice grains. Zn concentrations were also found to be higher when Zn was added to the basic culture medium, and La concentrations in grains were too low to be measured. Additionally, grain 2-AP concentrations were significantly and positively correlated with proline concentrations, ProDH activities in grains and 2-AP in culture medium. In summary, higher grain 2-AP concentrations might be due to Zn- and La-induced increases in proline concentrations and ProDH activities, as well as the direct uptake and transportation of 2-AP from the culture medium. Furthermore, application of both Zn and La might be helpful for improving aroma formation in rice. However, interactions of both these elements with the complex process of 2-AP formation remain to be explored.

  10. Dyslipidemia and its relationship with antiphospholipid antibodies in APS patients in North Kerala

    PubMed Central

    Sadanand, Shajit; Paul, Binoy J; Thachil, Emil J; Meletath, Rejadheesh

    2016-01-01

    Objective Antiphospholipid antibody syndrome (APS) is one of the most common acquired thrombophilic disorders resulting in arterial and venous thromboses. APS is a major cause for cerebrovascular accidents or stokes, myocardial infarction, venous thromboembolism and recurrent abortions/pregnancy losses especially in young patients. APS patients have an increased risk of atherosclerotic cardiovascular events. There are only two studies on lipid abnormalities in APS patients. None of them have studied the relationship between individual laboratory tests for APS and lipid profile abnormalities. Here we describe the significance of the relationship between various APS tests and lipid profile abnormalities in a subset of APS patients who presented with arterial thrombosis in a tertiary care hospital. Material and Methods The study was conducted at Government Medical College, which is a tertiary care referral hospital. All patients who presented to the medicine department with APS during a two-year period were studied. A patient was considered to be positive for anticardiolipin (aCL) antibody or anti-β2 glycoprotein (anti-β2G) if the titer was more than 15 IU/mL, and a high titer was considered to be more than 40 IU/mL for Immunoglobulin (lg) IgG and IgM isotypes. The fasting lipid profile was measured in all patients, and lipid profile abnormalities were defined with cutoffs of low-density lipoprotein (LDL) levels of >150 mg/dL, triglyceride (TG) levels of >150 mg/dL, and high-density lipoprotein (HDL) levels of <40 mg/dL. The relationship between lipid abnormalities and individual tests for APS, aCL IgG and IgM and anti-β2G IgG and IgM, were determined by statistical analysis. Results The study population included 77 APS patients, with 53% of patients between 20 and 40 years. The commonest abnormality in the lipid profile test was elevated TG levels of >150 mg/dL in 51.9% of the patients, followed by low HDL levels (<40 mg/dL) in 38.9% of the patients and high LDL

  11. A novel nucleolar transcriptional activator ApLLP for long-term memory formation is intrinsically unstructured but functionally active.

    PubMed

    Liu, Jingxian; Song, Jianxing

    2008-02-08

    A novel Aplysia nucleolar protein ApLLP has been recently characterized to be a transcriptional activator that binds to the cAMP-response element (CRE) and thus induces ApC/EBP expression required for establishing long-term memory. So far, no structural information is available for both ApLLP and its homologs. Here, we expressed the entire ApLLP and its two dissected fragments, followed by structural and binding studies using CD and NMR spectroscopy. The study leads to two interesting findings: (1) all three ApLLP proteins are highly disordered, owning no predominant secondary and tertiary structures; (2) ApLLP is capable of binding the CRE DNA element but this induces no significant change in its secondary and tertiary structures. Intriguingly, it appears that the DNA-binding residues are mainly located on the C-half of the ApLLP molecule. Taken together, our results define ApLLP as an intrinsically unstructured protein and may bear important implications in understanding the molecular mechanism underlying ApLLP functions.

  12. Impaired dynamin 2 function leads to increased AP-1 transcriptional activity through the JNK/c-Jun pathway.

    PubMed

    Szymanska, Ewelina; Skowronek, Agnieszka; Miaczynska, Marta

    2016-01-01

    Activation of AP-1 transcription factors, composed of the Jun and Fos proteins, regulates cellular fates, such as proliferation, differentiation or apoptosis. Among other stimuli, the AP-1 pathway can be initiated by extracellular ligands, such as growth factors or cytokines, which undergo internalization in complex with their receptors. Endocytosis has been implicated in the regulation of several signaling pathways; however its possible impact on AP-1 signaling remains unknown. Here we show that inhibition of dynamin 2 (Dyn2), a major regulator of endocytic internalization, strongly stimulates the AP-1 pathway. Specifically, expression of a dominant-negative Dyn2 K44A mutant increases the total levels of c-Jun, its phosphorylation on Ser63/73 and transcription of AP-1 target genes. Interestingly, DNM2 mutations implicated in human neurological disorders exhibit similar effects on AP-1 signaling. Mechanistically, Dyn2 K44A induces AP-1 by increasing phosphorylation of several receptor tyrosine kinases. Their activation is required to initiate a Src- and JNK-dependent signaling cascade converging on c-Jun and stimulating expression of AP-1 target genes. Cumulatively, our data uncover a link between the Dyn2 function and JNK signaling which leads to AP-1 induction.

  13. Inactivation of AP1 proteins by a nuclear serine protease precedes the onset of radiation-induced fibrosing alveolitis.

    PubMed

    Haase, Michael G; Klawitter, Anke; Bierhaus, Angelika; Yokoyama, Kazunari K; Kasper, Michael; Geyer, Peter; Baumann, Michael; Baretton, Gustavo B

    2008-05-01

    Radiation-induced lung damage comprises inflammation (alveolitis) as well as disturbed regulation of cell differentiation and proliferation (fibrosis). The transcriptional regulation of this process is poorly understood. One key transcription factor involved in the regulation of proliferation and differentiation is AP1 (activator protein 1). The present study examined changes in the DNA-binding activity of AP1 after irradiation and defined the underlying molecular mechanisms in an animal model. The right lungs of Fischer rats received a single radiation dose of 20 Gy. Lung tissue was tested for AP1 DNA-binding activity, AP1 mRNA, and levels of AP1 proteins as well as for c-Jun specific proteolytic activity. After an initial increase, the AP1 DNA-binding activity was completely lost starting at 5.5 weeks after irradiation, which is 2.5 weeks before the onset of fibrosing alveolitis. This was not caused by reduction of mRNA levels or size. Instead, a selective nuclear cleavage of c-Jun by a serine protease caused the loss of AP1 activity. Considering the central role of AP1 in cell proliferation and differentiation and the strict timely correlation to the onset of the disease, the complete loss of AP1 function is likely to play a critical role in radiation-induced fibrosing alveolitis.

  14. AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

    PubMed Central

    Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

    2014-01-01

    Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

  15. Structural Basis for the Recognition of Histone H4 by the Histone-Chaperone RbAp46

    PubMed Central

    Murzina, Natalia V.; Pei, Xue-Yuan; Zhang, Wei; Sparkes, Mike; Vicente-Garcia, Jose; Pratap, J. Venkatesh; McLaughlin, Stephen H.; Ben-Shahar, Tom Rolef; Verreault, Alain; Luisi, Ben F.; Laue, Ernest D.

    2008-01-01

    Summary RbAp46 and RbAp48 (pRB-associated proteins p46 and p48, also known as RBBP7 and RBBP4, respectively) are highly homologous histone chaperones that play key roles in establishing and maintaining chromatin structure. We report here the crystal structure of human RbAp46 bound to histone H4. RbAp46 folds into a seven-bladed β propeller structure and binds histone H4 in a groove formed between an N-terminal α helix and an extended loop inserted into blade six. Surprisingly, histone H4 adopts a different conformation when interacting with RbAp46 than it does in either the nucleosome or in the complex with ASF1, another histone chaperone. Our structural and biochemical results suggest that when a histone H3/H4 dimer (or tetramer) binds to RbAp46 or RbAp48, helix 1 of histone H4 unfolds to interact with the histone chaperone. We discuss the implications of our findings for the assembly and function of RbAp46 and RbAp48 complexes. PMID:18571423

  16. 75 FR 1831 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP1000...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... Evaluation Report associated with the amendment to the Westinghouse AP1000 Design Certification Document and... discussions with Westinghouse, Southern Nuclear Operating Company (SNC), and NRC staff...

  17. Disruption of AP1S1, Causing a Novel Neurocutaneous Syndrome, Perturbs Development of the Skin and Spinal Cord

    PubMed Central

    Drouin, Christian A.; Lapointe, Line; Boudreau, Michèle; Meloche, Caroline; Drouin, Régen; Hudson, Thomas J.; Drapeau, Pierre; Cossette, Patrick

    2008-01-01

    Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit σ1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord. PMID:19057675

  18. EjAP2-1, an AP2/ERF gene, is a novel regulator of fruit lignification induced by chilling injury, via interaction with EjMYB transcription factors.

    PubMed

    Zeng, Jiao-Ke; Li, Xian; Xu, Qian; Chen, Jian-Ye; Yin, Xue-Ren; Ferguson, Ian B; Chen, Kun-Song

    2015-12-01

    Lignin biosynthesis is regulated by many transcription factors, such as those of the MYB and NAC families. However, the roles of AP2/ERF transcription factors in lignin biosynthesis have been rarely investigated. Eighteen EjAP2/ERF genes were isolated from loquat fruit (Eriobotrya japonica), which undergoes postharvest lignification during low temperature storage. Among these, expression of EjAP2-1, a transcriptional repressor, was negatively correlated with fruit lignification. The dual-luciferase assay indicated that EjAP2-1 could trans-repress activities of promoters of lignin biosynthesis genes from both Arabidopsis and loquat. However, EjAP2-1 did not interact with the target promoters (Ej4CL1). Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated protein-protein interactions between EjAP2-1 and lignin biosynthesis-related EjMYB1 and EjMYB2. Furthermore, repression effects on the Ej4CL1 promoter were observed with the combination of EjAP2-1 and EjMYB1 or EjMYB2, while EjAP2-1 with the EAR motif mutated (mEjAP2-1) lost such repression, although mEjAP2-1 still interacted with EjMYB protein. Based on these results, it is proposed that EjAP2-1 is an indirect transcriptional repressor on lignin biosynthesis, and the repression effects were manifested by EAR motifs and were conducted via protein-protein interaction with EjMYBs.

  19. EVALUATION OF THE TEMPORARY TENT COVER TRUSS SYSTEM AP PRIMARY VENT SYSTEM

    SciTech Connect

    HAQ MA

    2009-12-31

    The purpose of this calculation is to evaluate a temporary ten cover truss system. This system will be used to provide weather protection to the workers during replacement of the filter for the Primary Ventilation System in AP Tank Farm. The truss system has been fabricated utilizing tubes and couplers, which are normally used for scaffoldings.

  20. Thermodynamics of Damaged DNA Binding and Catalysis by Human AP Endonuclease 1.

    PubMed

    Miroshnikova, A D; Kuznetsova, A A; Kuznetsov, N A; Fedorova, O S

    2016-01-01

    Apurinic/apyrimidinic (AP) endonucleases play an important role in DNA repair and initiation of AP site elimination. One of the most topical problems in the field of DNA repair is to understand the mechanism of the enzymatic process involving the human enzyme APE1 that provides recognition of AP sites and efficient cleavage of the 5'-phosphodiester bond. In this study, a thermodynamic analysis of the interaction between APE1 and a DNA substrate containing a stable AP site analog lacking the C1' hydroxyl group (F site) was performed. Based on stopped-flow kinetic data at different temperatures, the steps of DNA binding, catalysis, and DNA product release were characterized. The changes in the standard Gibbs energy, enthalpy, and entropy of sequential specific steps of the repair process were determined. The thermodynamic analysis of the data suggests that the initial step of the DNA substrate binding includes formation of non-specific contacts between the enzyme binding surface and DNA, as well as insertion of the amino acid residues Arg177 and Met270 into the duplex, which results in the removal of "crystalline" water molecules from DNA grooves. The second binding step involves the F site flipping-out process and formation of specific contacts between the enzyme active site and the everted 5'-phosphate-2'-deoxyribose residue. It was shown that non-specific interactions between the binding surfaces of the enzyme and DNA provide the main contribution into the thermodynamic parameters of the DNA product release step.

  1. Testing the presence of lithium on the surfaces of cool Ap stars

    NASA Astrophysics Data System (ADS)

    Nesvacil, N.; Hubrig, S.; Mathys, G.

    2004-12-01

    The possibility of a quite high Li abundance in the Ap stars was first raised by Wallerstein & Merchant (1965). Since then many studies investigated the problem of Li. The more recent observations in the lithium region indicate that in some Ap stars the λ 6708 feature is variable and this variability can be explained by the existence of Li rich spots on the stellar surface. Atomic data for the Ce II λ 6708.099 were released by the D.R.E.A.M. database in 2002. The line was used to identify the prominent suspected Li-feature in post AGB stars and might as well be responsible for the absorption feature in Ap stars. Recent studies have mentioned this possibility, but it has yet to be investigated in more detail. Other physical phenomena, such as the occurrence of a partial Paschen-Back effect in the presence of magnetic fields, as well as possible hyperfine structure splitting of some Rare Earth transitions, must be taken into account to provide correct line identifications in the wavelength region around the Li-doublet at λ 6708. We discuss a possible strategy to clarify the presence of Li in Ap stars.

  2. AP-IO: asynchronous pipeline I/O for hiding periodic output cost in CFD simulation.

    PubMed

    Xiaoguang, Ren; Xinhai, Xu

    2014-01-01

    Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%.

  3. Structure of AP205 Coat Protein Reveals Circular Permutation in ssRNA Bacteriophages.

    PubMed

    Shishovs, Mihails; Rumnieks, Janis; Diebolder, Christoph; Jaudzems, Kristaps; Andreas, Loren B; Stanek, Jan; Kazaks, Andris; Kotelovica, Svetlana; Akopjana, Inara; Pintacuda, Guido; Koning, Roman I; Tars, Kaspars

    2016-10-23

    AP205 is a single-stranded RNA bacteriophage that has a coat protein sequence not similar to any other known single-stranded RNA phage. Here, we report an atomic-resolution model of the AP205 virus-like particle based on a crystal structure of an unassembled coat protein dimer and a cryo-electron microscopy reconstruction of the assembled particle, together with secondary structure information from site-specific solid-state NMR data. The AP205 coat protein dimer adopts the conserved Leviviridae coat protein fold except for the N-terminal region, which forms a beta-hairpin in the other known single-stranded RNA phages. AP205 has a similar structure at the same location formed by N- and C-terminal beta-strands, making it a circular permutant compared to the other coat proteins. The permutation moves the coat protein termini to the most surface-exposed part of the assembled particle, which explains its increased tolerance to long N- and C-terminal fusions.

  4. Supporting document for the historical tank content estimate for AP-tank farm

    SciTech Connect

    Brevick, C.H.; Stroup, J.L.; Funk, J.W., Fluor Daniel Hanford

    1997-03-06

    This Supporting Document provides historical in-depth characterization information on AP-Tank Farm, such as historical waste transfer and level data, tank physical information, temperature plots, liquid observation well plots, chemical analyte and radionuclide inventories for the Historical Tank Content Estimate Report for the Southeast Quadrant of the Hanford 200 Areas.

  5. Specific activation of human interleukin-5 depends on de novo synthesis of an AP-1 complex.

    PubMed

    Schwenger, Gretchen T F; Kok, Chee Choy; Arthaningtyas, Estri; Thomas, Marc A; Sanderson, Colin J; Mordvinov, Viatcheslav A

    2002-12-06

    It is clear from the biology of eosinophilia that a specific regulatory mechanism must exist. Because interleukin-5 (IL5) is the key regulatory cytokine, it follows that a gene-specific control of IL5 expression must exist that differs even from closely related cytokines such as IL4. Two features of IL5 induction make it unique compared with other cytokines; first, induction by cyclic adenosine monophosphate (cAMP), which inhibits other T-cell-derived cytokines, and second, sensitivity to protein synthesis inhibitors, which have no effect on other cytokines. This study has utilized the activation of different transcription factors by different stimuli in a human T-cell line to study the role of conserved lymphokine element 0 (CLE0) in the specific induction of IL5. In unstimulated cells the ubiquitous Oct-1 binds to CLE0. Stimulation induces de novo synthesis of the AP-1 members JunD and Fra-2, which bind to CLE0. The amount of IL5 produced correlates with the production of the AP-1 complex, suggesting a key role in IL5 expression. The formation of the AP-1 complex is essential, but the rate-limiting step is the synthesis of AP-1, especially Fra-2. This provides an explanation for the sensitivity of IL5 to protein synthesis inhibitors and a mechanism for the specific induction of IL5 compared with other cytokines.

  6. Development of cotton gin PM10 emission factors for EPA’s AP-42

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Compilation of Air Pollution Emission Factors (AP-42) emission factors are assigned ratings, from A (Excellent) to E (Poor), based on the quality of data used to develop them. All current PM10 cotton gin emission factors received quality ratings of D or lower. In an effort to improve these ratin...

  7. Update on the development of cotton gin PM10 emission factors for EPA's AP-42

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A cotton ginning industry-supported project was initiated in 2008 to update the U.S. Environmental Protection Agency’s (EPA) Compilation of Air Pollution Emission Factors (AP-42) to include PM10 emission factors. This study develops emission factors from the PM10 emission factor data collected from ...

  8. Evaluating EPA’s AP-42 development methodology using a cotton gin total PM dataset

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” has yet to be widely used. These ...

  9. Westinghouse AP1000 Advanced Plant Simplification Results,Measures,and Benefits

    SciTech Connect

    Paulson, C.K.

    2002-07-01

    A clear distinction between advanced plants, such as the Westinghouse AP1000 and AP600, and evolutionary plants is the policy in the latter to use current systems' and buildings' configurations. This approach does not promote simplification or streamlining, especially in the mechanical systems of the plant. The most significant simplification in evolutionary designs has arguably been in the plant electronics where compact digital components and multiplexing have led to improvements, especially in the areas of information display, installation, and testing. The Westinghouse advanced, passive plants take a different approach. Their design engineers presume that if regulatory requirements can be satisfied by using passive systems, then active plant systems that are only designed to meet plant control functions and not burdened with meeting a safety pedigree can be implemented. This separation of safety and control allows the plant designer to focus on systems' optimization and reliability by reducing complexity and its associated cost. This design policy has led Westinghouse to the AP600 and AP1000 plant configurations, both of which incorporate significant improvements in areas of plant simplification and enhanced safety. (authors)

  10. The 7th Annual AP[R] Report to the Nation

    ERIC Educational Resources Information Center

    College Board, 2011

    2011-01-01

    This report shows how well educators across the United States have increased access to the types of rich academic experiences that prepare students for success in college. By combining national, state and AP (Advanced Placement) data, this report provides educators and policymakers with information they can use to celebrate their successes,…

  11. Ultrasonic Examination of Double-Shell Tank 241-AP-103. Examination Completed April 2003.

    SciTech Connect

    Pardini, Allan F.; Posakony, Gerald J.

    2003-06-30

    COGEMA Engineering Corporation (COGEMA), under contract from CH2M Hill Hanford Group (CH2M Hill), has performed an ultrasonic examination of selected portions of Double-Shell Tank 241-AP-103. PNNL is responsible for preparing a report(s)that describes the results of the COGEMA ultrasonic examinations.

  12. Ultraviolet photometry from the orbiting astronomical observatory. 8: The blue Ap stars

    NASA Technical Reports Server (NTRS)

    Leckrone, D. S.

    1973-01-01

    The filter photometers in the Wisconsin Experiment Package on OAO-2 were used to obtain data for a carefully selected set of 24 blue Ap stars and 31 comparison standard B and A dwarfs and giants for a program of relative photometry. Observations were made in seven bandpasses over the effective wavelength range 1430A-4250A. The Ap stars observed include members of the Si, Hg-Mn and Sr-Cr-Eu peculiarity classes. Most of them are too blue in B-V for their published MK spectral classes. The blue Ap stars are markedly deficient in emitted ultraviolet flux and are underluminous as compared to normal stars with the same UBV colors. The Hg-Mn stars appear less flux deficient in the ultraviolet for their UBV colors than do Si or Sr-cr-Eu stars. Most of the Ap stars observed possess ultraviolet flux distributions, or ultraviolet color temperatures, consistent with their published MK spectral classes to well within the classification uncertainties.

  13. Retinoic acid is a negative regulator of AP-1-responsive genes.

    PubMed Central

    Schüle, R; Rangarajan, P; Yang, N; Kliewer, S; Ransone, L J; Bolado, J; Verma, I M; Evans, R M

    1991-01-01

    We present evidence that retinoic acid can down-regulate transcriptional activation by the nuclear protooncogene c-jun. All three members of the retinoic acid receptor (RAR) subfamily (RAR alpha, RAR beta, and RAR gamma) can repress transcriptional induction of the human collagenase gene or a heterologous promoter that contains the collagenase promoter AP-1-binding site. In contrast, the retinoid X receptor fails to repress Jun/AP-1 activity, demonstrating a significant difference between the two regulatory systems through which retinoids exert their transcriptional control. Analysis of RAR alpha mutants in transfection studies reveals that the DNA-binding domain is important for the inhibition of Jun/AP-1 activity, even though the RAR does not bind the collagenase AP-1 site. Rather, gel-retardation assays reveal that bacterially expressed full-length RAR alpha inhibits binding of Jun protein to target DNA. These data suggest that the RAR alpha may form a nonproductive complex with c-Jun and provides a simple mechanisms by which retinoic acid may limit cell growth and possibly malignant progression. Images PMID:1648728

  14. Monitoring Physiology Trainee Needs to Focus Professional Society Responses: The APS Trainee Needs Surveys

    ERIC Educational Resources Information Center

    Matyas, Marsha L.; Lowy, Melinda E.; Sweazea, Karen L.; Alvarez, Diego F.

    2011-01-01

    In 2004 and 2007, the American Physiological Society (APS) Trainee Advisory Committee (TAC) conducted surveys of graduate students, postdoctoral fellows, and new investigators in physiology to identify topics and issues important to those trainees. Two major trends emerged from the data. First, trainees in 2007 expressed somewhat greater interest…

  15. DETAIL VIEW OF AP 47E AND ITS WINCH, MAIN FLOOR ...

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

    DETAIL VIEW OF AP 47E AND ITS WINCH, MAIN FLOOR LEVEL, PLATFORM E-SOUTH, HB-3, FACING NORTHEAST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  16. DETAIL VIEW OF AP 47W AND ITS WINCH, MAIN FLOOR ...

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

    DETAIL VIEW OF AP 47W AND ITS WINCH, MAIN FLOOR LEVEL, PLATFORM E-SOUTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  17. The long life of an endocytic patch that misses AP-2.

    PubMed

    de León, Nagore; Valdivieso, M-Henar

    2016-11-01

    Endocytosis is the process by which cells regulate extracellular fluid uptake and internalize molecules bound to their plasma membrane. This process requires the generation of protein-coated vesicles. In clathrin-mediated endocytosis (CME) the assembly polypeptide 2 (AP-2) adaptor facilitates rapid endocytosis of some plasma membrane receptors by mediating clathrin recruitment to the endocytic site and by connecting cargoes to the clathrin coat. While this adaptor is essential for early embryonic development in mammals, initial results suggested that it is dispensable for endocytosis in unicellular eukaryotes. The drastic effect of depleting AP-2 in metazoa and the mild effect of deleting AP-2 subunits in Saccharomyces cerevisiae have prevented a detailed analysis of the dynamics of endocytic patches in the absence of this adaptor. Using live-cell imaging of Schizosaccharomyces pombe endocytic sites we have shown that eliminating AP-2 perturbs the dynamics of endocytic patches beyond the moment of coat assembly. These perturbations affect the cell growth pattern and cell wall synthesis. Our results highlight the importance of using different model organisms to address the study of conserved aspects of CME.

  18. Purification and characterization of the Streptococcus salivarius methionine aminopeptidase (MetAP).

    PubMed

    Boufous, El Houssine; Vadeboncoeur, Christian

    2003-10-01

    Streptococcus salivarius methionine aminopeptidase (MetAP) was purified from a recombinant Escherichia coli strain containing the S. salivarius map gene, which codes for MetAP. S. salivarius map coded for a protein of 286 amino acids with a calculated molecular mass of 31,723 Da and a pI of 4.6. The native enzyme eluted from a Superdex column as a protein with a molecular mass of 30.6 kDa and cleaved N-terminal Met of peptide only when the penultimate amino acid was Gly, Ala, Ser, Val, Pro, or Thr. The enzyme was more active against tetrapeptides than tripeptides and did not recognize dipeptides. It required the presence of a metal cation for activity, with a preference for Co(2+) over Mn(2+). S. salivarius MetAP has a pH optimum of 8.0 and an optimal temperature at 50 degrees C. The S. salivarius protein had an extra sequence of 24 amino acids between two conserved aspartate residues involved in the coordination of the metal ion. A similar extra sequence is present in MetAP from other streptococci and from Lactococcus lactis, but not from other bacteria or eukaryotes.

  19. Understanding Predictors of Enrollment in Advanced Placement (AP) Coursework among Latina/o Students

    ERIC Educational Resources Information Center

    Cavazos, Lionel Javier, Jr.

    2012-01-01

    The purpose of this study was to (a) determine the extent to which Latina/o students' perceptions of support from high school teachers and counselors, as well as acculturation, predict enrollment in AP coursework; (b) examine Latina/o students' perceptions of different forms of support that appear to play a role in academic success (Hassinger…

  20. Aviation Safety Program: Weather Accident Prevention (WxAP) Project Overview and Status

    NASA Technical Reports Server (NTRS)

    Nadell, Shari-Beth

    2003-01-01

    This paper presents a project overview and status for the Weather Accident Prevention (WxAP) aviation safety program. The topics include: 1) Weather Accident Prevention Project Background/History; 2) Project Modifications; 3) Project Accomplishments; and 4) Project's Next Steps.

  1. Comparing Recent Organizing Templates for Test Content between ACS Exams in General Chemistry and AP Chemistry

    ERIC Educational Resources Information Center

    Holme, Thomas

    2014-01-01

    Two different versions of "big ideas" rooted content maps have recently been published for general chemistry. As embodied in the content outline from the College Board, one of these maps is designed to guide curriculum development and testing for advanced placement (AP) chemistry. The Anchoring Concepts Content Map for general chemistry…

  2. Clathrin assembly proteins AP180 and CALM in the embryonic rat brain

    PubMed Central

    Schwartz, Catherine M.; Cheng, Aiwu; Mughal, Mohamed R.; Mattson, Mark P.; Yao, Pamela J.

    2010-01-01

    Clathrin-coated vesicles are known to play diverse and pivotal roles in cells. The proper formation of clathrin-coated vesicles is dependent on, and highly regulated by, a large number of clathrin assembly proteins. These assembly proteins likely determine the functional specificity of clathrin-coated vesicles, and together they control a multitude of intracellular trafficking pathways—including those involved in embryonic development. In this study, we focus on two closely related clathrin assembly proteins, AP180 and CALM (clathrin assembly lymphoid myeloid leukemia protein), in the developing embryonic rat brain. We find that AP180 begins to be expressed at embryonic day 14 (E14), but only in postmitotic cells that have acquired a neuronal fate. CALM, on the other hand, is expressed as early as E12, by both neural stem cells and postmitotic neurons. In vitro loss-of-function studies using RNA interference (RNAi) indicate that AP180 and CALM are dispensable for some aspects of embryonic neurogenesis but are required for the growth of postmitotic neurons. These results identify the developmental staging of AP180 and CALM expression and suggest that each protein has distinct functions in neural development. PMID:20653035

  3. Sample Selection Effect on AP Multiple-Choice Score to Composite Score Scaling.

    ERIC Educational Resources Information Center

    Yang, Wen-Ling; Dorans, Neil J.; Tateneni, Krishna

    Scores on the multiple-choice sections of alternate forms are equated through anchor-test equating for the Advanced Placement Program (AP) examinations. There is no linkage of free-response sections since different free-response items are given yearly. However, the free-response and multiple-choice sections are combined to produce a composite.…

  4. Tank characterization report for double-shell Tank 241-AP-107

    SciTech Connect

    DeLorenzo, D.S.; Simpson, B.C.

    1994-09-06

    The purpose of this tank characterization report is to describe and characterize the waste in Double-Shell Tank 241-AP-107 based on information gathered from various sources. This report summarizes the available information regarding the waste in Tank 241-AP-107, and arranges it in a useful format for making management and technical decisions concerning this particular waste tank. In addition, conclusion and recommendations based on safety and further characterization needs are given. Specific objectives reached by the sampling and characterization of the waste in Tank 241-AP-107 are: Contribute toward the fulfillment of the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) Milestone M-44-05 concerning the characterization of Hanford Site high-level radioactive waste tanks; Complete safety screening of the contents of Tank 241-AP-107 to meet the characterization requirements of the Defense Nuclear Facilities Safety board (DNFSB) Recommendation 93-5; and Provide tank waste characterization to the Tank Waste Remediation System (TWRS) Program Elements in accordance with the TWRS Tank Waste Analysis Plan.

  5. First photometric study of two southern eclipsing binaries IS Tel and DW Aps

    NASA Astrophysics Data System (ADS)

    Özer, S.; Sürgit, D.; Erdem, A.; Öztürk, O.

    2017-02-01

    The paper presents the first photometric analysis of two southern eclipsing binary stars, IS Tel and DW Aps. Their V light curves from the All Sky Automated Survey were modelled by using Wilson-Devinney method. The final models give these two Algol-like binary stars as having detached configurations. Absolute parameters of the components of the systems were also estimated.

  6. Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

    PubMed

    Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

  7. Another Strategy for Teaching Histology to A&P Students: Classification versus Memorization.

    ERIC Educational Resources Information Center

    Bavis, Ryan W.; Seveyka, Jerred; Shigeoka, Cassie A.

    2000-01-01

    Defines dichotomous keys as common learning tools based on identification rather than memorization. Provides an example of a dichotomous key developed for introducing histology in human anatomy and physiology (A&P) courses and explains how students can use the dichotomous key. Discusses the goals of the exercises and the process of…

  8. AP1000{sup R} severe accident features and post-Fukushima considerations

    SciTech Connect

    Scobel, J. H.; Schulz, T. L.; Williams, M. G.

    2012-07-01

    The AP1000{sup R} passive nuclear power plant is uniquely equipped to withstand an extended station blackout scenario such as the events following the earthquake and tsunami at Fukushima without compromising core and containment integrity. The AP1000 plant shuts down the reactor, cools the core, containment and spent fuel pool for more than 3 days using passive systems that do not require AC or DC power or operator actions. Following this passive coping period, minimal operator actions are needed to extend the operation of the passive features to 7 days using installed equipment. To provide defense-in-depth for design extension conditions, the AP1000 plant has engineered features that mitigate the effects of core damage. Engineered features retain damaged core debris within the reactor vessel as a key feature. Other aspects of the design protect containment integrity during severe accidents, including unique features of the AP1000 design relative to passive containment cooling with water and air, and hydrogen management. (authors)

  9. Automated Procurement System (APS): Project management plan (DS-03), version 1.2

    NASA Technical Reports Server (NTRS)

    Murphy, Diane R.

    1994-01-01

    The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) is implementing an Automated Procurement System (APS) to streamline its business activities that are used to procure goods and services. This Project Management Plan (PMP) is the governing document throughout the implementation process and is identified as the APS Project Management Plan (DS-03). At this point in time, the project plan includes the schedules and tasks necessary to proceed through implementation. Since the basis of APS is an existing COTS system, the implementation process is revised from the standard SDLC. The purpose of the PMP is to provide the framework for the implementation process. It discusses the roles and responsibilities of the NASA project staff, the functions to be performed by the APS Development Contractor (PAI), and the support required of the NASA computer support contractor (CSC). To be successful, these three organizations must work together as a team, working towards the goals established in this Project Plan. The Project Plan includes a description of the proposed system, describes the work to be done, establishes a schedule of deliverables, and discusses the major standards and procedures to be followed.

  10. DIFFERENTIAL ACTIVATION OF AP-1 IN HUMAN BLADDER EPITHELIAL CELLS BY INORGANIC AND METHYLATED ARSENICALS

    EPA Science Inventory

    Differential Activation of AP-1 in Human Bladder Epithelial Cells by Inorganic and Methylated Arsenicals

    Zuzana Drobna, Ilona Jaspers, David J. Thomas, and Miroslav Styblo

    ABSTRACT

    Epidemiological studies have linked chronic ingestion of drinking water contai...

  11. 10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11 of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1...,” (FSER), then the generic DCD controls. E. Design activities for structures, systems, and components that... Commission has determined that the structures, systems, components, and design features of the AP600...

  12. 10 CFR Appendix D to Part 52 - Design Certification Rule for the AP1000 Design

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1, Tier...,” Supplement No. 2, then the generic DCD controls. E. Design activities for structures, systems, and components... the structures, systems, components, and design features of the AP1000 design comply with...

  13. 10 CFR Appendix D to Part 52 - Design Certification Rule for the AP1000 Design

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1, Tier... structures, systems, and components that are wholly outside the scope of this appendix may be performed using... the structures, systems, components, and design features of the AP1000 design comply with...

  14. 10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 11 of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1...,” (FSER), then the generic DCD controls. E. Design activities for structures, systems, and components that... Commission has determined that the structures, systems, components, and design features of the AP600...

  15. 10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1...,” (FSER), then the generic DCD controls. E. Design activities for structures, systems, and components that... Commission has determined that the structures, systems, components, and design features of the AP600...

  16. 10 CFR Appendix D to Part 52 - Design Certification Rule for the AP1000 Design

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1, Tier...,” Supplement No. 2, then the generic DCD controls. E. Design activities for structures, systems, and components... the structures, systems, components, and design features of the AP1000 design comply with...

  17. 10 CFR Appendix D to Part 52 - Design Certification Rule for the AP1000 Design

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1, Tier... structures, systems, and components that are wholly outside the scope of this appendix may be performed using... the structures, systems, components, and design features of the AP1000 design comply with...

  18. 10 CFR Appendix D to Part 52 - Design Certification Rule for the AP1000 Design

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1, Tier...,” Supplement No. 2, then the generic DCD controls. E. Design activities for structures, systems, and components... the structures, systems, components, and design features of the AP1000 design comply with...

  19. 10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 11 of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1...,” (FSER), then the generic DCD controls. E. Design activities for structures, systems, and components that... Commission has determined that the structures, systems, components, and design features of the AP600...

  20. 10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 11 of the Atomic Energy Act of 1954, as amended, as applicable. III. Scope and Contents A. Tier 1...,” (FSER), then the generic DCD controls. E. Design activities for structures, systems, and components that... Commission has determined that the structures, systems, components, and design features of the AP600...

  1. Developing an Understanding of Variation: AP Statistics Teachers' Perceptions and Recollections of Critical Moments

    ERIC Educational Resources Information Center

    Peters, Susan A.

    2009-01-01

    This phenomenological study investigates conceptions of statistical variation that secondary mathematics teachers who are recognized leaders in AP Statistics exhibit. This study also investigates perceptions and recollections of activities and actions that teachers who exhibited robust understandings of variation suggest contributed to their…

  2. U.S. Government Assistance to AP's World-Wide Expansion.

    ERIC Educational Resources Information Center

    Renaud, Jean-Luc

    1985-01-01

    Examines the activities of K. Cooper, an early general manager of the Associated Press, and explores what appears to be a contradiction between his insistance on unhampered international news flow and his desire to receive government aid in order to expand AP's operations abroad. (FL)

  3. Ultrasonic Examination of Double-Shell Tank 241-AP-107 Examination Completed February 2008.

    SciTech Connect

    Pardini, Allan F.; Weier, Dennis R.; Anderson, Kevin K.

    2008-04-28

    AREVA NC Inc. (AREVA), under a contract from CH2M Hill Hanford Group (CH2M Hill), has performed an ultrasonic examination of selected portions of Double-Shell Tank 241-AP-107. PNNL is responsible for preparing a report(s) that describes the results of the AREVA ultrasonic examinations.

  4. Using the Theory of Successful Intelligence as a Framework for Developing Assessments in AP Physics

    ERIC Educational Resources Information Center

    Stemler, Steven E.; Sternberg, Robert J.; Grigorenko, Elena L.; Jarvin, Linda; Sharpes, Kirsten

    2009-01-01

    A new test of Advanced Placement Physics, explicitly designed to balance both content and cognitive-processing skills, was developed using Sternberg's theory of successful intelligence. The test was administered to 281 AP Physics students from 10 schools during the 2006-2007 school year. Six empirically distinguishable profiles of strengths and…

  5. The Impact of AP and IB Programs on High Stakes College Admissions

    ERIC Educational Resources Information Center

    Chodl, Joseph

    2012-01-01

    The purpose of this study was to examine the impact on undergraduate college admissions decisions at selective U.S. colleges and universities of student enrolment in the Advanced Placement (AP) or International Baccalaureate (IB) programs of international schools. A total of 30 interviews were conducted by the researcher with admissions personnel…

  6. AP-3 and Rabip4’ Coordinately Regulate Spatial Distribution of Lysosomes

    PubMed Central

    Ivan, Viorica; Martinez-Sanchez, Emma; Sima, Livia E.; Oorschot, Viola; Klumperman, Judith; Petrescu, Stefana M.; van der Sluijs, Peter

    2012-01-01

    The RUN and FYVE domain proteins rabip4 and rabip4’ are encoded by RUFY1 and differ in a 108 amino acid N-terminal extension in rabip4’. Their identical C terminus binds rab5 and rab4, but the function of rabip4s is incompletely understood. We here found that silencing RUFY1 gene products promoted outgrowth of plasma membrane protrusions, and polarized distribution and clustering of lysosomes at their tips. An interactor screen for proteins that function together with rabip4’ yielded the adaptor protein complex AP-3, of which the hinge region in the β3 subunit bound directly to the FYVE domain of rabip4’. Rabip4’ colocalized with AP-3 on a tubular subdomain of early endosomes and the extent of colocalization was increased by a dominant negative rab4 mutant. Knock-down of AP-3 had an ever more dramatic effect and caused accumulation of lysosomes in protrusions at the plasma membrane. The most peripheral lysosomes were localized beyond microtubules, within the cortical actin network. Our results uncover a novel function for AP-3 and rabip4’ in regulating lysosome positioning through an interorganellar pathway. PMID:23144738

  7. Displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor

    SciTech Connect

    Wang, Zujun Huang, Shaoyan; Liu, Minbo; Xiao, Zhigang; He, Baoping; Yao, Zhibin; Sheng, Jiangkun

    2014-07-15

    The experiments of displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor are presented. The CMOS APS image sensors are manufactured in the standard 0.35 μm CMOS technology. The flux of neutron beams was about 1.33 × 10{sup 8} n/cm{sup 2}s. The three samples were exposed by 1 MeV neutron equivalent-fluence of 1 × 10{sup 11}, 5 × 10{sup 11}, and 1 × 10{sup 12} n/cm{sup 2}, respectively. The mean dark signal (K{sub D}), dark signal spike, dark signal non-uniformity (DSNU), noise (V{sub N}), saturation output signal voltage (V{sub S}), and dynamic range (DR) versus neutron fluence are investigated. The degradation mechanisms of CMOS APS image sensors are analyzed. The mean dark signal increase due to neutron displacement damage appears to be proportional to displacement damage dose. The dark images from CMOS APS image sensors irradiated by neutrons are presented to investigate the generation of dark signal spike.

  8. Student Access to Advanced Placement[R] (AP[R]) Coursework: Principals' Beliefs and Practices

    ERIC Educational Resources Information Center

    Wood, Steven M.

    2010-01-01

    Advanced Placement[R] (AP[R]) courses provide high school students an opportunity to be exposed to the rigors of college while they are still in high school. Since school policies play a role in the opportunities for students to pursue these courses, educational leaders must be aware of the ways in which their personal beliefs and school practices…

  9. A Test of Strategies for Enhanced Learning of AP Descriptive Chemistry

    ERIC Educational Resources Information Center

    Kotcherlakota, Suhasini; Brooks, David W.

    2008-01-01

    The Advanced Placement (AP) Descriptive Chemistry Website allows users to practice chemistry problems. This study involved the redesign of the Website using worked examples to enhance learner performance. The population sample for the study includes users (students and teachers) interested in learning descriptive chemistry materials. The users…

  10. RAS/ERK pathway transcriptional regulation through ETS/AP-1 binding sites.

    PubMed

    Hollenhorst, Peter C

    2012-01-01

    The RAS/RAF/MEK/ERK signaling pathway is activated by mutation in many cancers. Neighboring ETS and AP-1 DNA binding sequences can act as response elements for transcriptional activation by this pathway. ERK phosphorylation of an ETS transcription factor is one mechanism of activating the RAS/ERK gene expression program that can promote cancer cell phenotypes such as proliferation, invasion, and metastasis. Recent genome-wide mapping of ETS proteins over-expressed by chromosomal rearrangement in prostate cancer reveals a second mechanism for activation of this gene expression program. An oncogenic subset of ETS transcription factors can activate RAS/ERK target genes even in the absence of RAS/ERK pathway activation by binding ETS/AP-1 sequences. Thus, regulation of cancer cell invasion and metastasis via ETS/AP-1 sequence elements depends on which ETS protein is bound, and the status of the RAS/ERK pathway. This commentary will focus on what is known about the selectivity of ETS/AP-1 sequences for different ETS transcription factors and the transcriptional consequences of ETS protein selection.

  11. Professional Development Aligned with AP Chemistry Curriculum: Promoting Science Practices and Facilitating Enduring Conceptual Understanding

    ERIC Educational Resources Information Center

    Herrington, Deborah G.; Yezierski, Ellen J.

    2014-01-01

    The recent revisions to the advanced placement (AP) chemistry curriculum promote deep conceptual understanding of chemistry content over more rote memorization of facts and algorithmic problem solving. For many teachers, this will mean moving away from traditional worksheets and verification lab activities that they have used to address the vast…

  12. AP1000{sup R} design robustness against extreme external events - Seismic, flooding, and aircraft crash

    SciTech Connect

    Pfister, A.; Goossen, C.; Coogler, K.; Gorgemans, J.

    2012-07-01

    Both the International Atomic Energy Agency (IAEA) and the U.S. Nuclear Regulatory Commission (NRC) require existing and new nuclear power plants to conduct plant assessments to demonstrate the unit's ability to withstand external hazards. The events that occurred at the Fukushima-Dai-ichi nuclear power station demonstrated the importance of designing a nuclear power plant with the ability to protect the plant against extreme external hazards. The innovative design of the AP1000{sup R} nuclear power plant provides unparalleled protection against catastrophic external events which can lead to extensive infrastructure damage and place the plant in an extended abnormal situation. The AP1000 plant is an 1100-MWe pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance and safety. The plant's compact safety related footprint and protection provided by its robust nuclear island structures prevent significant damage to systems, structures, and components required to safely shutdown the plant and maintain core and spent fuel pool cooling and containment integrity following extreme external events. The AP1000 nuclear power plant has been extensively analyzed and reviewed to demonstrate that it's nuclear island design and plant layout provide protection against both design basis and extreme beyond design basis external hazards such as extreme seismic events, external flooding that exceeds the maximum probable flood limit, and malicious aircraft impact. The AP1000 nuclear power plant uses fail safe passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems (such as AC power, component cooling water, service water, compressed air or HVAC). The plant has been designed to protect systems, structures, and components critical to placing the reactor in a safe shutdown condition within the steel containment vessel

  13. AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

    SciTech Connect

    Gorgemans, J.; Mulhollem, L.; Glavin, J.; Pfister, A.; Conway, L.; Schulz, T.; Oriani, L.; Cummins, E.; Winters, J.

    2012-07-01

    The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first level of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all possible pool

  14. Atmospheric delay analysis from GPS meteorology and InSAR APS

    NASA Astrophysics Data System (ADS)

    Cheng, Shilai; Perissin, Daniele; Lin, Hui; Chen, Fulong

    2012-09-01

    Radar atmospheric decorrelation due to inhomogeneity of atmospheric refractivity is a critical limitation of satellite SAR interferometry (InSAR) in the high accuracy retrieving of geophysical parameters. With mm precision, a water vapor tracing technique based on GPS meteorology was widely employed to mitigate InSAR atmospheric errors. However, a reliable comparison of atmospheric delay between GPS and InSAR is rarely touched, mainly due to the scarcity of stable and accurate InSAR atmospheric phases. In the paper we propose a comparison methodology between GPS Zenith Tropospheric Delay (ZTD) and SAR Atmospheric Phase Screen (APS) in both differential and pseudo-absolute modes. In the experiment, ENVISAT ASAR APS maps and synchronous GPS campaign measurements in Como, Italy were collected for consistency analysis. Furthermore, the stratification effect of atmospheric delay, in a form of delay-to-elevation ratios, was particularly analyzed for the purpose of separating different components within APSs. Finally, with the above stratification analysis, terms of stratification and assumed turbulence from SAR APS and GPS were compared in differential mode. Presented results show that the stratified ratios from GPS delays and SAR APS maps are in agreement with a std of 7.7 mm/km and a bias of 3.4 mm/km. Correlation coefficients of stratified ratios are higher than 0.7 in ascending case. In differential mode, the atmospheric total delays coincide with STandard Deviations (STDs) smaller than 4 mm (∼0.65 mm PWV) and with correlation coefficients higher than 0.6. The comparison of total delays in ‘pseudo-absolute’ mode is provided as an alternative vision of the agreement between GPS and InSAR. The agreement in this mode was slightly worse than that in differential mode. STDs of the difference are smaller than 6 mm (∼1 mm PWV), and the correlation coefficients are about 0.5 for different implementation approaches. Above comparison results in the work provide a

  15. A Comparison of Van Allen Belt Radiation Environment Modeling Programs: AE8/AP8 Legacy, AE9/AP9, and SPENVIS

    NASA Technical Reports Server (NTRS)

    Reed, Evan; Pellish, Jonathan

    2016-01-01

    In the space surrounding Earth there exists an active radiation environment consisting mostly of electrons and protons that have been trapped by Earths magnetic field. This radiation, also known as the Van Allen Belts, has the potential to damage man-made satellites in orbit; thus, proper precautions must be taken to shield NASA assets from this phenomenon. Data on the Van Allen Belts has been collected continuously by a multitude of space-based instruments since the beginning of space exploration. Subsequently, using theory to fill in the gaps in the collected data, computer models have been developed that take in the orbital information of a hypothetical mission and output the expected particle fluence and flux for that orbit. However, as new versions of the modeling system are released, users are left wondering how the new version differs from the old. Therefore, we performed a comparison of three different editions of the modeling system: AE8/AP8 (legacy), which is included in the model 9 graphical user interface as an option for ones calculations, AE9/AP9, and the Space Environment Information System (SPENVIS), which is an online-based form of AE8/AP8 developed by NASA and the European Space Agency that changed the code to allow the program to extrapolate data to predict fluence and flux at higher energies. Although this evaluation is still ongoing, it is predicted that the model 8 (legacy) and SPENVIS version will have identical outputs with the exception of the extended energy levels from SPENVIS, while model 9 will provide different fluences than model 8 based on additional magnetic field descriptions and on-orbit data.

  16. An Insider's History of Some of the Significant Changes In the APS from the 1960s to Today

    NASA Astrophysics Data System (ADS)

    Schwartz, Brian

    2014-03-01

    It has been over 50 years since I first joined the American Physical Society. A lot has changed. The APS in the 60s did not have a single Forum and all divisions were related to sub-field of physics research plus the History of Physics Division. The APS governance and meeting's structure did not provide for issues relate to physics and society, undergraduate and graduate education, minorities, women, industrial physics, international physics, communication of science, and many more subjects quite typical of APS in 2014. From the start, I was a very active member of APS and one of the original petitioners for the Division on Physics and Society. Ultimately this led to the APS Forum structure, the Panel on Public Affairs and many APS formal committees. Two of the major impetuses for change in the late 60s were the need to debate the role of science in the unpopular war in Vietnam and the overproduction and poor employment prospects for new Ph.D.s. I, and colleagues, (with little original encouragement from the APS leadership), arranged for the discussion on many new topics at the meeting and proposed changes within the governance of the Society. In the late 1980s I joined the APS and was involved in many changes over the next 20 years. ultimately as Associate Executive Officer and Director of the APS Centennial in 1999. As indicated earlier, I've been with the APS for over 50 years and will present its history as a participant-insider. Topic covered include my surprise election to the APS governance in 1972, the establishment of the Forum on Physics and Society (and the restrictions imposed on its governance), my role as the father (or mother) of the women's movement at APS, the complexities and politics of the move of APS headquarters from New York to College Park, the establishment of the tabloid APS News and many more subjects. Currently I am producing staged-readings of science-based plays at the March and April 2014 APS meetings for the Forum on History of

  17. Isoform-specific degradation of PR-B by E6-AP is critical for normal mammary gland development.

    PubMed

    Ramamoorthy, Sivapriya; Dhananjayan, Sarath C; Demayo, Francesco J; Nawaz, Zafar

    2010-11-01

    E6-associated protein (E6-AP), which was originally identified as an ubiquitin-protein ligase, also functions as a coactivator of estrogen (ER-α) and progesterone (PR) receptors. To investigate the in vivo role of E6-AP in mammary gland development, we generated transgenic mouse lines that either overexpress wild-type (WT) human E6-AP (E6-AP(WT)) or ubiquitin-protein ligase-defective E6-AP (E6-AP(C833S)) in the mammary gland. Here we show that overexpression of E6-AP(WT) results in impaired mammary gland development. In contrast, overexpression of E6-AP(C833S) or loss of E6-AP (E6-AP(KO)) increases lateral branching and alveolus-like protuberances in the mammary gland. We also show that the mammary phenotypes observed in the E6-AP transgenic and knockout mice are due, in large part, to the alteration of PR-B protein levels. We also observed alteration in ER-α protein level, which might contribute to the observed mammary phenotype by regulating PR expression. Furthermore, E6-AP regulates PR-B protein levels via the ubiquitin-proteasome pathway. Additionally, we also show that E6-AP impairs progesterone-induced Wnt-4 expression by decreasing the steady state level of PR-B in both mice and in human breast cancer cells. In conclusion, we present the novel observation that E6-AP controls mammary gland development by regulating PR-B protein turnover via the ubiquitin proteasome pathway. For the first time, we show that the E3-ligase activity rather than the coactivation function of E6-AP plays an important role in the mammary gland development, and the ubiquitin-dependent PR-B degradation is not required for its transactivation functions. This mechanism appears to regulate normal mammogenesis, and dysregulation of this process may be an important contributor to mammary cancer development and progression.

  18. The RNA-binding protein RBPMS1 represses AP-1 signaling and regulates breast cancer cell proliferation and migration.

    PubMed

    Fu, Jie; Cheng, Long; Wang, Yu; Yuan, Ping; Xu, Xiaojie; Ding, Lihua; Zhang, Hao; Jiang, Kai; Song, Haifeng; Chen, Zhongwu; Ye, Qinong

    2015-01-01

    The activator protein-1 (AP-1) transcription factor complex plays a crucial role in tumor growth and progression. However, how AP-1 transcriptional activity is repressed is not fully understood. Here, we show that RNA-binding protein with multiple splicing 1 (RBPMS1) physically and functionally interacts with AP-1 in vitro and in vivo. The RNA-recognition motif (RRM) and C-terminus of the RBPMS1 isoforms RBPMS1A and RBPMS1C, but not RBPMS1B, interacted with cFos, a member of the AP-1 family that dimerizes with cJun to stimulate AP-1 transcriptional activity. RBPMS1 did not associate with Jun proteins. RBPMS1A and RBPMS1C bound to the basic leucine zipper (bZIP) domain of cFos that mediates dimerization of AP-1 proteins. In addition, RBPMS1A-C interacted with the transcription factor Smad3, which was shown to interact with cJun and increase AP-1 transcriptional activity. RBPMS1 inhibited c-Fos or Smad3-mediated AP-1 transactivation and the expression of AP-1 target genes known to be the key regulators of cancer growth and progression, including vascular endothelial growth factor (VEGF) and cyclin D1. Mechanistically, RBPMS1 blocks the formation of the cFos/cJun or Smad3/cJun complex as well as the recruitment of cFos or Smad3 to the promoters of AP-1 target genes. In cultured cells and a mouse xenograft model, RBPMS1 inhibited the growth and migration of breast cancer cells through c-Fos or Smad3. These data suggest that RBPMS1 is a critical repressor of AP-1 signaling and RBPMS1 activation may be a useful strategy for cancer treatment.

  19. An AP-3-dependent mechanism drives synaptic-like microvesicle biogenesis in pancreatic islet beta-cells.

    PubMed

    Suckow, Arthur T; Craige, Branch; Faundez, Victor; Cain, William J; Chessler, Steven D

    2010-07-01

    Pancreatic islet beta-cells contain synaptic-like microvesicles (SLMVs). The origin, trafficking, and role of these SLMVs are poorly understood. In neurons, synaptic vesicle (SV) biogenesis is mediated by two different cytosolic adaptor protein complexes, a ubiquitous AP-2 complex and the neuron-specific AP-3B complex. Mice lacking AP-3B subunits exhibit impaired GABAergic (inhibitory) neurotransmission and reduced neuronal vesicular GABA transporter (VGAT) content. Since beta-cell maturation and exocytotic function seem to parallel that of the inhibitory synapse, we predicted that AP-3B-associated vesicles would be present in beta-cells. Here, we test the hypothesis that AP-3B is expressed in islets and mediates beta-cell SLMV biogenesis. A secondary aim was to test whether the sedimentation properties of INS-1 beta-cell microvesicles are identical to those of bona fide SLMVs isolated from PC12 cells. Our results show that the two neuron-specific AP-3 subunits beta3B and mu3B are expressed in beta-cells, the first time these proteins have been found to be expressed outside the nervous system. We found that beta-cell SLMVs share the same sedimentation properties as PC12 SLMVs and contain SV proteins that sort specifically to AP-3B-associated vesicles in the brain. Brefeldin A, a drug that interferes with AP-3-mediated SV biogenesis, inhibits the delivery of AP-3 cargoes to beta-cell SLMVs. Consistent with a role for AP-3 in the biogenesis of GABAergic SLMV in beta-cells, INS-1 cell VGAT content decreases upon inhibition of AP-3 delta-subunit expression. Our findings suggest that beta-cells and neurons share molecules and mechanisms important for mediating the neuron-specific membrane trafficking pathways that underlie synaptic vesicle formation.

  20. E6-AP/UBE3A protein acts as a ubiquitin ligase toward SOX9 protein.

    PubMed

    Hattori, Takako; Kishino, Tetsuya; Stephen, Shelley; Eberspaecher, Heidi; Maki, Sayumi; Takigawa, Masaharu; de Crombrugghe, Benoit; Yasuda, Hideyo

    2013-12-06

    SOX9 is a transcription factor that acts as a key regulator at various stages of cartilage differentiation. There is ample evidence that intracellular SOX9 protein levels are tightly regulated both by sumoylation and by degradation through the ubiquitin-proteasome pathway. Using a proteomics approach, here we report the identification of a SOX9-binding protein, E6-AP/UBE3A, that may act as a ubiquitin ligase toward Sox9. E6-AP bound SOX9 through the region consisting mostly of its high mobility group domain in vitro. In nuclear lysates, FLAG-tagged E6-AP coprecipitated with Sox9 and its high mobility group domain. This finding was estimated using nuclear lysates from a chondrocytic cell line that endogenously expresses E6-AP and SOX9. Accordingly, ectopically expressed E6-AP and SOX9 colocalized in the nucleus. We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes by E6-AP and degraded by proteasomes. This is in accordance with the distribution of SOX9 levels, which are high in proliferating and prehypertrophic chondrocytes but low in hypertrophic chondrocytes, whereas E6-AP levels are high in hypertrophic chondrocytes and low in prehypertrophic chondrocytes. Furthermore, E6-AP-deficient mice showed SOX9 accumulation in chondrocytes and the brain. These findings support the concept that E6-AP regulates SOX9 levels in developing cartilage by acting as a ubiquitin ligase.