PREFACE: Rusnanotech 2010 International Forum on Nanotechnology

NASA Astrophysics Data System (ADS)

Kazaryan, Konstantin

2011-03-01

The Rusnanotech 2010 International Forum on Nanotechnology was held from November 1-3, 2010, in Moscow, Russia. It was the third forum organized by RUSNANO (Russian Corporation of Nanotechnologies) since 2008. In March 2011 RUSNANO was established as an open joint-stock company through the reorganization of the state corporation Russian Corporation of Nanotechnologies. RUSNANO's mission is to develop the Russian nanotechnology industry through co-investment in nanotechnology projects with substantial economic potential or social benefit. Within the framework of the Forum Science and Technology Program, presentations on key trends of nanotechnology development were given by foreign and Russian scientists, R&D officers of leading international companies, universities and scientific centers. The science and technology program of the Forum was divided into eight sections as follows (by following hyperlinks you may find each section's program including videos of all oral presentations): Catalysis and Chemical Industry Nanobiotechnology Nanodiagnostics Nanoelectronics Nanomaterials Nanophotonics Nanotechnolgy In The Energy Industry Nanotechnology in Medicine The scientific program of the forum included 115 oral presentations by leading scientists from 15 countries. Among them in the "Nanomaterials" section was the lecture by Dr Konstantin Novoselov, winner of the Nobel Prize in Physics 2010. The poster session consisted of over 500 presentations, 300 of which were presented in the framework of the young scientists' nanotechnology papers competition. This volume of the Journal of Physics: Conference Series includes a selection of 57 submissions. The scientific program committee: Prof Zhores Alferov, AcademicianVice-president of Russian Academy of Sciences, Nobel Prize winner, Russia, Chairman of the Program CommitteeProf Sergey Deev, Corresponding Member of Russian Academy of SciencesHead of the Laboratory of Molecular Immunology, M M Shemyakin and Yu A Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Russia, Deputy Chairman of the Program CommitteeProf Alexander Aseev, AcademicianVice-president of Russian Academy of Sciences Director, A V Rzhanov-Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, RussiaProf Sergey Bagaev, AcademicianDirector, Institute of Laser Physics, Siberian Branch of Russian Academy of Sciences, RussiaProf Alexander Gintsburg, Ademician, Russian Academy of Medical SciencesDirector Gamaleya Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, RussiaProf Anatoly Grigoryev, Academician, Russian Academy of Sciences, Russian Academy of Medical SciencesVice-president, Russian Academy of Medical Sciences, RussiaProf Michael Kovalchuk, RAS Corresponding MemberDirector, Kurchatov Institute Russian Scientific Center, RussiaProf Valery Lunin, AcademicianDean, Department of Chemistry, Lomonosov Moscow State University, RussiaProf Valentin Parmon, Academician, DirectorBoreskov Institute of Catalysis, Siberian Branch of Russian Academy of Sciences, RussiaProf Rem Petrov, AcademicianAdvisor, Russian Academy of Sciences, RussiaProf Konstantin Skryabin, AcademicianDirector, Bioinzheneriya Center, Russian Academy of Sciences, RussiaProf Vsevolod Tkachuk, Academician, Russian Academy of Sciences, Russian Academy of Medical SciencesDean, Faculty of Fundamental Medicine, Lomonosov Moscow State University, RussiaProf Vladimir Fortov, AcademicianDirector, Joint Institute for High Temperatures, Russian Academy of Sciences, RussiaProf Alexey Khokhlov, AcademicianVice Principal, Head of Innovation, Information and International Scientific Affairs Department, Lomonosov Moscow State University, RussiaProf Valery Bukhtiyarov, RAS Corresponding MemberDirector, Physicochemical Research Methods Dept., Boreskov Institute of Catalysis, Siberian Branch of Russian Academy of Sciences, RussiaProf Anatoly Dvurechensky, RAS Corresponding MemberDeputy Director, Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, RussiaProf Vladimir Kvardakov, Corresponding Member of Russian Academy of SciencesExecutive Director, Kurchatov Center of Synchrotron Radiation and Nanotechnology, RussiaProf Edward Son, Corresponding member of Russian Academy of SciencesScientific Deputy Director, Joint Institute for High Temperatures, Russian Academy of Sciences, RussiaProf Andrey GudkovSenior Vice President, Basic Science Chairman, Department of Cell Stress Biology, Roswell Park Cancer Institute, USAProf Robert NemanichChair, Department of Physics, Arizona State University, USAProf Kandlikar SatishProfessor, Rochester Institute of Technology, USAProf Xiang ZhangUC Berkeley, Director of NSF Nano-scale Science and Engineering Center (NSEC), USAProf Andrei ZvyaginProfessor, Macquarie University, AustraliaProf Sergey KalyuzhnyDirector of the Scientific and Technological Expertise Department, RUSNANO, RussiaKonstantin Kazaryan, PhDExpert of the Scientific and Technological Expertise Department, RUSNANO, Russia, Program Committee SecretarySimeon ZhavoronkovHead of Nanotechnology Programs Development Office, Rusnanotech Forum Fund for the Nanotechnology Development, Russia Editors of the proceedings: Section "Nanoelectronics" - Corresponding Member of Russian Academy of Sciences, Professor Anatoly Dvurechenskii (Institute of Semiconductor Physics, RAS).Section "Nanophotonics" - Professor Vasily Klimov (Institute of Physics, RAS).Section "Nanodiagnostics" - Professor P Kashkarov (Russian Scientific Center, Kurchatov Institute).Section "Nanotechnology for power engineering" - Corresponding Member of Russian Academy of Sciences, Professor Eduard Son (Joint Institute for High Temperatures, RAS).Section "Catalysis and chemical industry" - Member of Russian Academy of Sciences, Professor Valentin Parmon (Institute of Catalysis SB RAS).Section "Nanomaterials" - E Obraztsova, PhD (Institute of Physics, RAS), Marat Gallamov PhD (Moscow State University).Section "Nanotechnology in medicine" - Denis Logunov, PhD (Gamaleya Research Institute of Epidemiology and Microbiology, RAMS).Section "Nanobiotechnology" - Member of Russian Academy of Sciences, Professor Konstantin Skryabin (Bioengineering Center, RAS), Member of Russian Academy of Sciences, Professor Rem Petrov (RAS), Corresponding Member of Russian Academy of Sciences, Professor Sergey Deev (Institute of Bioorganic Chemistry).

70th anniversary of the E K Zavoisky Kazan Physical-Technical Institute, Kazan Scientific Center of the Russian Academy of Sciences (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 4 February 2016)

NASA Astrophysics Data System (ADS)

2016-06-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) was held on 4 February 2016 at the E K Zavoisky Kazan Physical-Technical Institute, Kazan Scientific Center (KSC), RAS, devoted to the 70th anniversary of the E K Zavoisky Kazan Physical-Technical Institute, KSC RAS. The agenda posted on the website of the Physical Sciences Division RAS http://www.gpad.ac.ru comprised the following reports: (1) Demishev S V (Prokhorov General Physics Institute, RAS, Moscow) "Quantum phase transitions in spiral magnets without an inversion center"; (2) Smirnov A I (Kapitza Institute for Physical Problems, RAS, Moscow) "Magnetic resonance of spinons in quantum magnets"; (3) Ryazanov V V (Institute of Solid State Physics, RAS, Chernogolovka, Moscow region) "Coherent and nonequilibrium phenomena in superconductor- and ferromagnet-based structures"; (4) Mel'nikov A S (Institute for Physics of Microstructures, RAS, Nizhny Novgorod) "Mechanisms of long-range proximity effects in superconducting spintronics"; (5) Fel'dman E B (Institute of Problems of Chemical Physics, RAS, Chernogolovka, Moscow region) "Magnus expansion paradoxes in the study of equilibrium magnetization and entanglement in multi-pulse spin locking"; (6) Fraerman A A (Institute for Physics of Microstructures, RAS, Nizhny Novgorod) "Features of the motion of spin-1/2 particles in a noncoplanar magnetic field"; (7) Salikhov K M (E K Zavoisky Kazan Physical-Technical Institute, KSC, RAS, Kazan) "Electron paramagnetic resonance applications: promising developments at the E K Zavoisky Kazan Physical-Technical Institute of the Russian Academy of Sciences"; (8) Vinogradov E A (Institute for Spectroscopy, RAS, Troitsk, Moscow) "Ultrathin film characterization using far-field surface polariton spectroscopy"; (9) Glyavin M Yu (Institute of Applied Physics, RAS, Nizhny Novgorod) "High-power terahertz sources for spectroscopy and material diagnostics"; (10) Soltamov V A (Ioffe Institute, RAS, Saint Petersburg) "Radio spectroscopy of the optically aligned spin states of color centers in silicon carbide"; (11) Kalachev A A (E K Zavoisky Kazan Physical-Technical Institute, KSC, RAS, Kazan) "Long-range quantum communication. Basic devices and prospects for development"; (12) Kuznetsov D (Bruker Corporation, Moscow) "Recent magnetic resonance hardware advances at the Bruker Corporation". Papers based on talks 1, 2, 4-7, 9, and 10 are presented below. • Quantum phase transitions in spiral magnets without an inversion center, S V Demishev, V V Glushkov, S V Grigoriev, M I Gilmanov, I I Lobanova, A N Samarin, A V Semeno, N E Sluchanko Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 559-563 • Magnetic resonance of spinons in quantum magnets, A I Smirnov Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 564-570 • Long-range ballistic transport mechanisms in superconducting spintronics, A V Samokhvalov, A S Mel'nikov, A I Buzdin Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 571-576 • Magnus expansion paradoxes in the study of equilibrium magnetization and entanglement in multi-pulse spin locking, E I Kuznetsova, E B Fel'dman, D E Feldman Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 577-582 • Features of the motion of spin-1/2 particles in a noncoplanar magnetic field, D A Tatarskiy, A V Petrenko, S N Vdovichev, O G Udalov, Yu V Nikitenko, A A Fraerman Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 583-587 • Electron paramagnetic resonance applications: promising developments at the E K Zavoisky Kazan Physical-Technical Institute of the Russian Academy of Sciences, K M Salikhov Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 588-594 • High power terahertz sources for spectroscopy and material diagnostics, M Yu Glyavin, G G Denisov, V E Zapevalov, M A Koshelev, M Yu Tretyakov, A I Tsvetkov Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 595-604 • Radio spectroscopy of the optically aligned spin states of color centers in silicon carbide, V A Soltamov, P G Baranov Physics-Uspekhi, 2016, Volume 59, Number 6, Pages 605-610

CONFERENCES AND SYMPOSIA Commemoration of the 85th birthday of S I Syrovatskii(Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 26 May 2010)

NASA Astrophysics Data System (ADS)

2010-12-01

A scientific session of the Physical Sciences Division, Russian Academy of Sciences (RAS), was held on 26 May 2010 at the conference hall of the Lebedev Physical Institute, RAS. The session was devoted to the 85th birthday of S I Syrovatskii. The program announced on the web page of the RAS Physical Sciences Division (www.gpad.ac.ru) contained the following reports: (1) Zelenyi L M (Space Research Institute, RAS, Moscow) "Current sheets and reconnection in the geomagnetic tail"; (2) Frank A G (Prokhorov General Physics Institute, RAS, Moscow) "Dynamics of current sheets as the cause of flare events in magnetized plasmas"; (3) Kuznetsov V D (Pushkov Institute of Terrestrial Magnetism, the Ionosphere, and Radio Wave Propagation, RAS, Troitsk, Moscow region) "Space research on the Sun"; (4) Somov B V (Shternberg Astronomical Institute, Lomonosov Moscow State University, Moscow) "Strong shock waves and extreme plasma states"; (5) Zybin K P (Lebedev Physical Institute, RAS, Moscow) "Structure functions for developed turbulence"; (6) Ptuskin V S (Pushkov Institute of Terrestrial Magnetism, the Ionosphere, and Radio Wave Propagation, RAS, Troitsk, Moscow region) "The origin of cosmic rays." Papers based on reports 1-4 and 6 are published in what follows. • Metastability of current sheets, L M Zelenyi, A V Artemyev, Kh V Malova, A A Petrukovich, R Nakamura Physics-Uspekhi, 2010, Volume 53, Number 9, Pages 933-941 • Dynamics of current sheets underlying flare-type events in magnetized plasmas, A G Frank Physics-Uspekhi, 2010, Volume 53, Number 9, Pages 941-947 • Space research of the Sun, V D Kuznetsov Physics-Uspekhi, 2010, Volume 53, Number 9, Pages 947-954 • Magnetic reconnection in solar flares, B V Somov Physics-Uspekhi, 2010, Volume 53, Number 9, Pages 954-958 • The origin of cosmic rays, V S Ptuskin Physics-Uspekhi, 2010, Volume 53, Number 9, Pages 958-961

Influence of spatial beam inhomogeneities on the parameters of a petawatt laser system based on multi-stage parametric amplification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frolov, S A; Trunov, V I; Pestryakov, Efim V

2013-05-31

We have developed a technique for investigating the evolution of spatial inhomogeneities in high-power laser systems based on multi-stage parametric amplification. A linearised model of the inhomogeneity development is first devised for parametric amplification with the small-scale self-focusing taken into account. It is shown that the application of this model gives the results consistent (with high accuracy and in a wide range of inhomogeneity parameters) with the calculation without approximations. Using the linearised model, we have analysed the development of spatial inhomogeneities in a petawatt laser system based on multi-stage parametric amplification, developed at the Institute of Laser Physics, Siberianmore » Branch of the Russian Academy of Sciences (ILP SB RAS). (control of laser radiation parameters)« less

Automatic estimation of dynamics of ionospheric disturbances with 1–15 minute lifetimes as derived from ISTP SB RAS fast chirp-ionosonde data

NASA Astrophysics Data System (ADS)

Berngardt, Oleg; Bubnova, Tatyana; Podlesnyi, Aleksey

2018-03-01

We propose and test a method of analyzing ionograms of vertical ionospheric sounding, which is based on detecting deviations of the shape of an ionogram from its regular (averaged) shape. We interpret these deviations in terms of reflection from the electron density irregularities at heights corresponding to the effective height. We examine the irregularities thus discovered within the framework of a model of a localized uniformly moving irregularity, and determine their characteristic parameters: effective heights and observed vertical velocities. We analyze selected experimental data for three seasons (spring, winter, autumn) obtained nearby Irkutsk with a fast chirp ionosonde of ISTP SB RAS in 2013-2015. The analysis of six days of observations conducted in these seasons has shown that in the observed vertical drift of the irregularities there are two characteristic distributions: wide velocity distribution with nearly 0 m/s mean and with the standard deviation of ∼250 m/s and narrow distribution with nearly -160 m/s mean. The analysis has demonstrated the effectiveness of the proposed algorithm for the automatic analysis of vertical sounding data with high repetition rate.

Educational process in modern climatology within the web-GIS platform "Climate"

NASA Astrophysics Data System (ADS)

Gordova, Yulia; Gorbatenko, Valentina; Gordov, Evgeny; Martynova, Yulia; Okladnikov, Igor; Titov, Alexander; Shulgina, Tamara

2013-04-01

These days, common to all scientific fields the problem of training of scientists in the environmental sciences is exacerbated by the need to develop new computational and information technology skills in distributed multi-disciplinary teams. To address this and other pressing problems of Earth system sciences, software infrastructure for information support of integrated research in the geosciences was created based on modern information and computational technologies and a software and hardware platform "Climate» (http://climate.scert.ru/) was developed. In addition to the direct analysis of geophysical data archives, the platform is aimed at teaching the basics of the study of changes in regional climate. The educational component of the platform includes a series of lectures on climate, environmental and meteorological modeling and laboratory work cycles on the basics of analysis of current and potential future regional climate change using Siberia territory as an example. The educational process within the Platform is implemented using the distance learning system Moodle (www.moodle.org). This work is partially supported by the Ministry of education and science of the Russian Federation (contract #8345), SB RAS project VIII.80.2.1, RFBR grant #11-05-01190a, and integrated project SB RAS #131.

Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis.

PubMed

Huling, Laura B; Baccaglini, Lorena; Choquette, Linda; Feinn, Richard S; Lalla, Rajesh V

2012-02-01

Recurrent aphthous stomatitis (RAS) is a common and painful oral mucosal disease. Possible etiologies include genetics, vitamin deficiencies, trauma, immune dysfunction, and stress. The goal of this study was to examine the relationship between the occurrence, type, and magnitude of stressful events and the onset and duration of RAS episodes. One hundred and sixty subjects with a history of RAS completed a weekly phone survey for up to 1 year, providing data on the occurrence of RAS episodes and details of any stressful events they experienced during the previous week. During RAS episodes, subjects also completed daily paper diaries that recorded incidence and duration of the RAS episode. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors. Stressful life events were significantly associated with the onset of RAS episodes (P < 0.001), however, not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54-4.72) than physical stressors (OR = 1.44; 95% CI = 1.04-1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity. In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors. © 2011 John Wiley & Sons A/S.

120th anniversary of the birth of Sergei Ivanovich Vavilov (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 30 March 2011)

NASA Astrophysics Data System (ADS)

2011-12-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) dedicated to the 120th anniversary of the birth of Sergei Ivanovich Vavilov was held in the Conference Hall of the P N Lebedev Physical Institute, RAS, on 30 March 2011. The following reports were put on the session's agenda posted on the web site www.gpad.ac.ru of the Physical Sciences Division, RAS: (1) Masalov A V (P N Lebedev Physical Institute, RAS, Moscow) "S I Vavilov and nonlinear optics"; (2) Basiev T T (Laser Materials and Technology Research Center, A M Prokhorov General Physics Institute, RAS, Moscow) "Luminescent nanophotonics and high-power lasers"; (3) Vitukhnovsky A G (P N Lebedev Physical Institute, RAS, Moscow) "Advances in luminescent light sources and displays"; (4) Aleksandrov E B (Ioffe Physical Technical Institute, RAS, St. Petersburg) "Sergei Ivanovich Vavilov and the special theory of relativity"; (5) Bolotovsky B M (P N Lebedev Physical Institute, RAS, Moscow) "Vavilov-Cherenkov effect"; (6) Vizgin V P (S I Vavilov Institute of the History of Natural Scienses and Technology, RAS, Moscow) "Sergei Ivanovich Vavilov as a historian of science"; (7) Ginzburg A S (Knowledge Society) "Academician S I Vavilov — a devotee of the enlightenment and the first president of the Knowledge Society of the USSR". The papers written on the basis of reports 1-4 and 6 are given below. The main contents of report 5 is reflected in the paper "Vavilov-Cherenkov radiation: its discovery and application" [Usp. Fiz. Nauk 179 1161 (2009); Phys. Usp. 52 1099 (2009)] published earlier by B M Bolotovsky. • S I Vavilov and nonlinear optics, A V Masalov, Z A Chizhikova Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1257-1262 • Luminescent nanophotonics, fluoride laser ceramics, and crystals, T T Basiev, I T Basieva, M E Doroshenko Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1262-1268 • Advances in light sources and displays, A G Vitukhnovsky Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1268-1272 • Direct experimental demonstration of the second special relativity postulate: the speed of light is independent of the speed of the source, E B Aleksandrov, P A Aleksandrov, V S Zapasskii, V N Korchuganov, A I Stirin Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1272-1278 • Sergei Ivanovich Vavilov as a historian of science, V P Vizgin, A V Kessenikh, K A Tomilin Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1278-1283

Aerodynamics of the EXPERT Re-Entry Ballistic Vehicle

NASA Astrophysics Data System (ADS)

Kharitonov, A. M.; Adamov, N. P.; Mazhul, I. I.; Vasenyov, L. G.; Zvegintsev, V. I.; Muylaert, J. M.

2009-01-01

Since 2002 till now, experimental studies of the EXPERT reentry capsule have been performed in ITAM SB RAS wind tunnels. These studies have been performed in consecutive ISTC project No. 2109, 3151, and currently ongoing project No. 3550. The results of earlier studies in ITAM wind tunnels can be found in [1-4]. The present paper describes new data obtained for the EXPERT model.

Systematization of climate data in the virtual research environment on the basis of ontology approach

NASA Astrophysics Data System (ADS)

Alipova, K. A.; Bart, A. A.; Fazliev, A. Z.; Gordov, E. P.; Okladnikov, I. G.; Privezentsev, A. I.; Titov, A. G.

2017-11-01

The first version of a primitive OWL-ontology of collections climate and meteorological data of Institute of Monitoring of Climatic and Ecological Systems SB RAS is presented. The ontology is a component of expert and decision support systems intended for quick search for climate and meteorological data required for solution of a certain class of applied problems.

Near-Earth space hazards and their detection (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 27 March 2013)

NASA Astrophysics Data System (ADS)

2013-08-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS), titled "Near-Earth space hazards and their detection", was held on 27 March 2013 at the conference hall of the Lebedev Physical Institute, RAS. The agenda posted on the website of the Physical Sciences Division, RAS, http://www.gpad.ac.ru, included the following reports: (1) Emel'yanenko V V, Shustov B M (Institute of Astronomy, RAS, Moscow) "The Chelyabinsk event and the asteroid-comet hazard"; (2) Chugai N N (Institute of Astronomy, RAS, Moscow) "A physical model of the Chelyabinsk event"; (3) Lipunov V M (Lomonosov Moscow State University, Sternberg Astronomical Institute, Moscow) "MASTER global network of optical monitoring"; (4) Beskin G M (Special Astrophysical Observatory, RAS, Arkhyz, Karachai-Cirkassian Republic) "Wide-field optical monitoring systems with subsecond time resolution for the detection and study of cosmic threats". The expanded papers written on the base of oral reports 1 and 4 are given below. • The Chelyabinsk event and the asteroid-comet hazard, V V Emel'yanenko, B M Shustov Physics-Uspekhi, 2013, Volume 56, Number 8, Pages 833-836 • Wide-field subsecond temporal resolution optical monitoring systems for the detection and study of cosmic hazards, G M Beskin, S V Karpov, V L Plokhotnichenko, S F Bondar, A V Perkov, E A Ivanov, E V Katkova, V V Sasyuk, A Shearer Physics-Uspekhi, 2013, Volume 56, Number 8, Pages 836-842

Landscape dynamics assessment of dry climatic zones on the Baikal-Gobi transect from NDVI time series and field investigations data

NASA Astrophysics Data System (ADS)

Sayapina, D. O.; Zharnikova, M. A.; Tsydypov, B. Z.; Sodnomov, B. V.; Garmaev, E. Zh

2016-11-01

Starting in the eighties of the 20th century, the scientists of the Baikal Institute of Nature Management (BINM SB RAS) have been conducting field observations of the Transbaikalia geosystems transformation due to the change of climate and nature management. An utmost importance is placed on the study of a negative response of the land geosystems. This is shown through their deterioration, degradation, and desertification in particular. Through the years of research (1985-2015) in dry areas of the north of Central Asia, the scientists of the BINM SB RAS established a network of key sites for contact monitoring of the status and dynamics of the geosystems and the negative natural-anthropogenic processes along the Baikal-Gobi meridional transect (51-44° N, 105-107° E). The monitoring of the status and dynamics of the vegetation cover of some key sites is conducted by processing and analysis of multitemporal and multispectral Landsat and MODIS Terra imagery. An automatic analysis of the time variation of NDVI and a comparison with the progress of the index in the previous seasons are performed. The landscape indication of the key sites is made on the basis of satellite imagery and complete geobotanical descriptions. Landscape profiles and facies maps with natural boundaries are created.

Commemoration of the 90th anniversary of the birth of Andrei Dmitrievich Sakharov (Scientific session of the Physical Sciences Division, Russian Academy of Sciences, 25 May 2011)

NASA Astrophysics Data System (ADS)

2012-02-01

On 25 May 2011, the scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS), devoted to the 90th anniversary of Andrei Dmitrievich Sakharov's birthday, was held at the conference hall of the Lebedev Physical Institute, RAS.The agenda of the session announced on the website www.gpad.ac.ru of the PSD RAS contains the following reports: (1) Mesyats G A (Lebedev Physical Institute, RAS, Moscow) "Introduction. Greetings"; (2) Ritus V I (Lebedev Physical Institute, RAS, Moscow) "A D Sakharov: personality and fate"; (3) Altshuler B L (Lebedev Physical Institute, RAS, Moscow) "Scientific and public legacy of A D Sakharov today"; (4) Ilkaev R I (Russian Federal Nuclear Center 'All-Russian Research Institute of Experimental Physics', Sarov, Nizhny Novgorod region) "The path of a genius: Sakharov at KB-11"; (5) Novikov I D (Astrocosmic Center, Lebedev Physical Institute, RAS, Moscow) "Wormholes and the multielement Universe"; (6) Azizov E A (National Research Centre 'Kurchatov Institute', Moscow) "Tokamaks: 60 years later"; (7) Kardashev N S (Astrocosmic Center, Lebedev Physical Institute, RAS, Moscow) "Cosmic interferometers"; (8) Lukash V I (Lebedev Physical Institute, RAS, Moscow) "From the cosmological model to the Hubble flux formation"; (9) Grishchuk L P (Shternberg State Astronomical Institute, Lomonosov Moscow State University, Moscow; School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom) "Cosmological Sakharov oscillations and quantum mechanics of the early Universe". Articles based on reports 2-4, 6, 8, and 9 are published below. The content of report 5 is close to papers "Multicomponent Universe and astrophysics of wormholes" by I D Novikov, N S Kardashev, A A Shatskii [Phys. Usp. 50 965 (2007)] and "Dynamic model of a wormhole and the Multiuniverse model" by A A Shatskii, I D Novikov, N S Kardashev [Phys. Usp. 51 457 (2008)]. The content of report 7 is close to the paper "Radioastron - a radio telescope much larger than the Earth: scientific program" by N S Kardashev [Phys. Usp. 52 1127 (2009)]. • A D Sakharov: personality and fate, V I Ritus Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 170-175 • Andrei Sakharov today: lasting impact on science and society, B L Altshuler Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 176-182 • Sakharov at KB-11. The path of a genius, R I Ilkaev Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 183-189 • Tokamaks: from A D Sakharov to the present (the 60-year history of tokamaks), E A Azizov Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 190-203 • From the Cosmological Model to the generation of the Hubble flow, V N Lukash, E V Mikheeva, V N Strokov Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 204-209 • Cosmological Sakharov oscillations and quantum mechanics of the early Universe, L P Grishchuk Physics-Uspekhi, 2012, Volume 55, Number 2, Pages 210-216

PREFACE: VII Conference on Low Temperature Plasma in the Processes of Functional Coating Preparation

NASA Astrophysics Data System (ADS)

Nail, Kashapov

2016-01-01

The VII All-Russian (with international participation) Scientific Technical Conference "Low-temperature plasma during the deposition of functional coatings" took place from 4-7 November 2015 at the Academy of Sciences of the Republic of Tatarstan and the Kazan Federal University. The conference was attended by over 150 people from Russia and abroad. The participants proposed a wide range of issues affecting the theoretical and experimental aspects of the problems of the physics of low-temperature plasma. We heard the reports of experts from leading universities and research organizations in the field of plasma physics: Moscow State University, St. Petersburg State University, MEPhI, Tomsk Polytechnic University, Institute of High Current Electronics SB RAS, etc. A series of works were devoted to the study of thin films obtained by low-temperature plasma. This year, work dedicated to the related field of heat mass transfer in multiphase media and low-temperature plasma was also presented. Of special interest were reports on the exploration of gas discharges with liquid electrolytic electrodes and the study of dusty plasmas. Kashapov Nail, D.Sc., professor (Kazan Federal University)

100th anniversary of the birth of E M Lifshitz (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 26 March 2015)

NASA Astrophysics Data System (ADS)

2015-09-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences dedicated to the 100th anniversary of the birth of Academician E M Lifshitz was held in the conference hall of the institute of Physical Problems, RAS, on 26 March 2015. The agenda of the session announced on the website www.gpad.ac.ru of the PSD RAS contains the reports: (1) Khalatnikov I M (Landau Institute for Theoretical Physics, RAS, Moscow) "Problem of singularity in cosmology"; (2) Kats E I (Landau Institute for Theoretical Physics, RAS, Moscow) "Van der Waals, Casimir, and Lifshitz forces in soft matter"; (3) Volovik G E (Landau Institute for Theoretical Physics, RAS, Moscow) "Superfluids in rotation: Onsager-Feynman vortices and Landau-Lifshitz vortex sheets." Papers written on the basis of oral presentations 1-3 are published below. • Stochastic cosmology, perturbation theories, and Lifshitz gravity, I M Khalatnikov, A Yu Kamenshchik Physics-Uspekhi, 2015, Volume 58, Number 9, Pages 878-891 • Van der Waals, Casimir, and Lifshitz forces in soft matter, E I Kats Physics-Uspekhi, 2015, Volume 58, Number 9, Pages 892-896 • Superfluids in rotation: Landau-Lifshitz vortex sheets vs Onsager-Feynman vortices, G E Volovik Physics-Uspekhi, 2015, Volume 58, Number 9, Pages 897-905

From the history of physics (Scientific session of the General Meeting of the Physical Sciences Division of the Russian Academy of Sciences, 17 December 2012)

NASA Astrophysics Data System (ADS)

2013-05-01

A scientific session of the General Meeting of the Physical Sciences Division of the Russian Academy of Sciences (RAS) was held in the conference hall of the Lebedev Physical Institute, RAS on 17 December 2012.The following reports were put on the session's agenda posted on the website http://www.gpad.ac.ru of the RAS Physical Sciences Division: (1) Dianov E M (Fiber Optics Research Center, RAS, Moscow) "On the threshold of a peta era"; (2) Zabrodskii A G (Ioffe Physical Technical Institute, RAS, St. Petersburg) "Scientists' contribution to the great victory in WWII using the example of the Leningrad (now A F Ioffe) Physical Technical Institute"; (3) Ilkaev R I (Russian Federal Nuclear Center --- All-Russian Research Institute of Experimental Physics, Sarov) "Major stages of the Soviet Atomic Project"; (4) Cherepashchuk A M (Sternberg State Astronomical Institute of Lomonosov Moscow State University, Moscow) "History of the Astronomy history ". Papers written on the basis of the reports are published below. • On the Threshold of Peta-era, E M Dianov Physics-Uspekhi, 2013, Volume 56, Number 5, Pages 486-492 • Scientists' contribution to the Great Victory in WWII on the example of the Leningrad (now A F Ioffe) Physical Technical Institute, A G Zabrodskii Physics-Uspekhi, 2013, Volume 56, Number 5, Pages 493-502 • Major stages of the Atomic Project, R I Ilkaev Physics-Uspekhi, 2013, Volume 56, Number 5, Pages 502-509 • History of the Universe History, A M Cherepashchuk Physics-Uspekhi, 2013, Volume 56, Number 5, Pages 509-530

International Conference on the Methods of Aerophysical Research 98 "ICMAR 98". Part 3: Proceedings

DTIC Science & Technology

1998-01-01

the study of aerodynamic characteristics and heat transfer in the simplest machine, disk fan, are presented in the paper. FLOW PATTERNS New knowledge of... Aerodynamics of base combustion / Ed. S.N.B.Murthy. - New York: AIAA. 1976. 2. Baev V.K., Golovichev V.I., Tretyakov P.K. Combustion in Supersonic...Theoretical and Applied Mechanics SB RAS, 630090, Novosibirsk, Russia The development of short-duration aerodynamic wind tunnels requires perfection of

Factors determining electrostatic fields in molecular dynamics simulations of the Ras/effector interface.

PubMed

Ensign, Daniel L; Webb, Lauren J

2011-12-01

Using molecular dynamics simulations, we explore geometric and physical factors contributing to calculated electrostatic fields at the binding surface of the GTPase Ras with a spectroscopically labeled variant of a downstream effector, the Ras-binding domain of Ral guanine nucleotide dissociation stimulator (RalGDS). A related system (differing by mutation of one amino acid) has been studied in our group using vibrational Stark effect spectroscopy, a technique sensitive to electrostatic fields. Electrostatic fields were computed using the AMBER 2003 force field and averaged over snapshots from molecular dynamics simulation. We investigate geometric factors by exploring how the orientation of the spectroscopic probe changes on Ras-effector binding. In addition, we explore the physical origin of electrostatic fields at our spectroscopic probe by comparing contributions to the field from discrete components of the system, such as explicit solvent, residues on the Ras surface, and residues on the RalGDS surface. These models support our experimental hypothesis that vibrational Stark shifts are caused by Ras binding to its effector and not the structural rearrangements of the effector surface or probe reorientation on Ras-effector binding, for at least some of our experimental probes. These calculations provide physical insight into the origin, magnitude, and importance of electrostatic fields in protein-protein interactions and suggest new experiments to probe the field's role in protein docking. Copyright © 2011 Wiley-Liss, Inc.

Efficient Ga(As)Sb quantum dot emission in AlGaAs by GaAs intermediate layer

NASA Astrophysics Data System (ADS)

Loeber, Thomas Henning; Richter, Johannes; Strassner, Johannes; Heisel, Carina; Kimmle, Christina; Fouckhardt, Henning

2013-03-01

Ga(As)Sb quantum dots (QDs) are epitaxially grown in AlGaAs/GaAs in the Stranski-Krastanov mode. In the recent past we achieved Ga(As)Sb QDs in GaAs with an extremely high dot density of 9.8•1010 cm-2 by optimization of growth temperature, Sb/Ga flux pressure ratio, and coverage. Additionally, the QD emission wavelength could be chosen precisely with these growth parameters in the range between 876 and 1035 nm. Here we report a photoluminescence (PL) intensity improvement for the case with AlGaAs barriers. Again growth parameters and layer composition are varied. The aluminium content is varied between 0 and 90%. Reflectance anisotropy spectroscopy (RAS) is used as insitu growth control to determine growth rate, layer thickness, and AlGaAs composition. Ga(As)Sb QDs, directly grown in AlxGa1-xAs emit no PL signal, even with a very low x ≈ 0.1. With additional around 10 nm thin GaAs intermediate layers between the Ga(As)Sb QDs and the AlGaAs barriers PL signals are detected. Samples with 4 QD layers and AlxGa1-xAs/GaAs barriers in between are grown. The thickness and composition of the barriers are changed. Depending on these values PL intensity is more than 4 times as high as in the case with simple GaAs barriers. With these results efficient Ga(As)Sb QD lasers are realized, so far only with pure GaAs barriers. Our index-guided broad area lasers operate continuous-wave (cw) @ 90 K, emit optical powers of more than 2•50 mW and show a differential quantum efficiency of 54% with a threshold current density of 528 A/cm2.

Pulsed UV laser technologies for ophthalmic surgery

NASA Astrophysics Data System (ADS)

Razhev, A. M.; Chernykh, V. V.; Bagayev, S. N.; Churkin, D. S.; Kargapol'tsev, E. S.; Iskakov, I. A.; Ermakova, O. V.

2017-01-01

The paper provides an overview of the results of multiyear joint researches of team of collaborators of Institute of Laser Physics SB RAS together with NF IRTC “Eye Microsurgery” for the period from 1988 to the present, in which were first proposed and experimentally realized laser medical technologies for correction of refractive errors of known today as LASIK, the treatment of ophthalmic herpes and open-angle glaucoma. It is proposed to carry out operations for the correction of refractive errors the use of UV excimer KrCl laser with a wavelength of 222 nm. The same laser emission is the most suitable for the treatment of ophthalmic herpes, because it has a high clinical effect, combined with many years of absence of recrudescence. A minimally invasive technique of glaucoma operations using excimer XeCl laser (λ=308 nm) is developed. Its wavelength allows perform all stages of glaucoma operations, while the laser head itself has high stability and lifetime, will significantly reduce operating costs, compared with other types of lasers.

Ilya Mikhailovich Lifshitz — 100th birthday anniversary

NASA Astrophysics Data System (ADS)

Grosberg, A. Y.

2018-01-01

On 18 January 2017, a scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) was held at the conference hall of the P N Lebedev Physical Institute, RAS, in honor of the 100th anniversary of the birth of I M Lifshitz. The following reports were put on the session agenda as posted on the PSD website http://www.gpad.ac.ru: (1) Grosberg A Yu (New York University, USA) "Ilya Mikhailovich Lifshitz and physics of biopolymers"; (2) Pastur L A (B I Verkin Institute for Low Temperature Physics \\& Engineering, National Academy of Sciences of Ukraine, Kharkiv) "Disordered fermions"; (3) Volovik G E (L D Landau Institute for Theoretical Physics, RAS, Moscow; Aalto University, Finland) "Exotic Lifshitz transitions in topological materials"; (4) Krapivskii P (Boston University, USA) "Lifshitz-Slyozov-Wagner theory and social dynamics"; (5) Gorsky A S (Institute for Information Transmission Problems, Moscow) "New critical phenomena in random networks and multiparticle localization"; (6) Nechaev S K (P N Lebedev Physical Institute, RAS, Moscow; Interdisciplinary Scientific Center Poncelet, Moscow) "Rare event statistics and hierarchy: from Lifshitz tails to modular invariance". Papers based on oral reports 1, 3, and 6 are given below.

Econophysics and evolutionary economics (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 2 November 2010)

NASA Astrophysics Data System (ADS)

2011-07-01

The scientific session "Econophysics and evolutionary economics" of the Division of Physical Sciences of the Russian Academy of Sciences (RAS) took place on 2 November 2010 in the conference hall of the Lebedev Physical Institute, Russian Academy of Sciences. The session agenda announced on the website www.gpad.ac.ru of the RAS Physical Sciences Division listed the following reports: (1) Maevsky V I (Institute of Economics, RAS, Moscow) "The transition from simple reproduction to economic growth"; (2) Yudanov A Yu (Financial University of the Government of the Russian Federation, Moscow) "Experimental data on the development of fast-growing innovative companies in Russia"; (3) Pospelov I G (Dorodnitsyn Computation Center, RAS, Moscow) "Why is it sometimes possible to successfully model an economy? (4) Chernyavskii D S (Lebedev Physical Institute, RAS, Moscow) "Theoretical economics"; (5) Romanovskii M Yu (Prokhorov Institute of General Physics, RAS, Moscow) "Nonclassical random walks and the phenomenology of fluctuations of the yield of securities in the securities market"; (6) Dubovikov M M, Starchenko N V (INTRAST Management Company, Moscow Engineering Physics Institute, Moscow) "Fractal analysis of financial time series and the prediction problem"; Papers written on the basis of these reports are published below. • The transition from simple reproduction to economic growth, V I Maevsky, S Yu Malkov Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 729-733 • High-growth firms in Russia: experimental data and prospects for the econophysical simulation of economic modernization, A Yu Yudanov Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 733-737 • Equilibrium models of economics in the period of a global financial crisis, I G Pospelov Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 738-742 • On econophysics and its place in modern theoretical economics, D S Chernavskii, N I Starkov, S Yu Malkov, Yu V Kosse, A V Shcherbakov Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 742-749 • Nonclassical random walks and the phenomenology of fluctuations of securities returns in the stock market, P V Vidov, M Yu Romanovsky Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 749-753 • Econophysics and the fractal analysis of financial time series, M M Dubovikov, N V Starchenko Physics-Uspekhi, 2011, Volume 54, Number 7, Pages 754-761

Digital Automation and Real-Time Monitoring of an Original Installation for "Wet Combustion" of Organic Wastes

NASA Astrophysics Data System (ADS)

Morozov, Yegor; Tikhomirov, Alexander A.; Saltykov, Mikhail; Trifonov, Sergey V.; Kudenko, D.. Yurii A.

2016-07-01

An original method for "wet combustion" of organic wastes, which is being developed at the IBP SB RAS, is a very promising approach for regeneration of nutrient solutions for plants in future spacecraft closed Bioregenerative Life Support Systems (BLSS). The method is quick, ecofriendly, does not require special conditions such as high pressure and temperature, and the resulting nitrogen stays in forms easy for further preparation of the fertilizer. An experimental testbed of a new-generation closed ecosystem is being currently run at the IBP SB RAS to examine compatibility of the latest technologies for accelerating the cycling. Integration of "wet combustion" of organic wastes into the information system of closed ecosystem experimental testbed has been studied as part of preparatory work. Digital automation and real-time monitoring of original "wet combustion" installation operation parameters have been implemented. The new system enabled remotely controlled or automatic work of the installation. Data are stored in standard easily processed formats, allowing further mathematical processing where necessary. During ongoing experiments on improving "wet combustion" of organic wastes, automatic monitoring can notice slight changes in process parameters and record them in more detail. The ultimate goal of the study is to include the "wet combustion" installation into future full-scale experiment with humans, thus reducing the time spent by the crew on life support issues while living in the BLSS. The work was carried out with the financial support of the Russian Scientific Foundation (project 14-14-00599).

Some possibilities of a closure degree increase and matter turnover intensification in the bioregenerative life support system BIOS-3

NASA Astrophysics Data System (ADS)

Tikhomirov, A. A.; Ushakova, S. A.; Velichko, V. V.; Degermendzhy, Á. G.; Lasseur, Ch.; Lamaze, B.

The problems of scientific-technical substantiation of perspective joint IBP-ESA works on imitation of functioning of stationary bioregenerative life support systems BLSS on Moon and or Mars are discussed With this purpose the possibilities of matter turnover intensification and closure degree increase which can be achieved after modernization of the BIOS-3 BLSS designed and constructed at Institute of Biophysics Siberian Branch of Russian Academy of Sciences IBP SB RAS Russia are considered These works are performed in the frame of INTAS IA project under the joint SB RAS-ESA financial support Specifically at the expense of intensity increase of photosynthetic active radiation from 150 to 250 Wt m 2 the productivity of photosynthesizing unit on oxygen and biomass is supposed to increase on 50 on average The given substantiation is based upon analysis of carried out preliminary experiments in a laboratory environment and in the BIOS-3 facility and also on series of experiments carried out at present time The results of technical reconstruction of lighting and thermoregulation systems demonstrating practical possibility of these plans implementation are produced On the grounds of mass exchange processes intensification the problems of a crew supply with vegetarian food and oxygen under a smaller photosynthesizing unit size are considered Some possibilities of the humans wastes utilization under combination of physicochemical and biological methods and necessary technical decisions allowing closure increase of matter turnover are

Comparison of accelerometer-measured sedentary behavior, and light- and moderate-to-vigorous-intensity physical activity in white- and blue-collar workers in a Japanese manufacturing plant.

PubMed

Fukushima, Noritoshi; Kitabayashi, Makiko; Kikuchi, Hiroyuki; Sasai, Hiroyuki; Oka, Koichiro; Nakata, Yoshio; Tanaka, Shigeho; Inoue, Shigeru

2018-05-25

The times spent in sedentary behavior (SB) and moderate-to-vigorous physical activity (MVPA) are independently associated with health outcomes; however, objective data on physical activity levels including SB among different occupations is limited. We compared accelerometer-measured times spent in SB, light-intensity physical activity (LPA), and MVPA, and the patterns associated with prolonged bouts of SB between white- and blue-collar workers. The study population consisted of 102 full-time plant workers (54 white-collar and 48 blue-collar) who wore a triaxial accelerometer during waking hours for 5 working days. Accelerometer-measured activity levels were categorized as SB (≤1.5 metabolic equivalents (METs)), LPA (1.6-2.9 METs), and MVPA (≥3.0 METs). A sedentary bout was defined as consecutive minutes during which the accelerometer registered less than ≤1.5 METs. Accelerometer variables were compared between white- and blue-collar workers through analysis of covariance. During working hours, white-collar workers spent significantly more time in SB and less time in LPA than blue-collar workers (SB: 6.4 h vs. 4.8 h, 73% vs. 55% of total work time; LPA: 1.9 h vs. 3.5 h, 22% vs. 40% of total work time, p<.001), whereas the MVPA time was similar between the groups. White-collar workers spent significantly more SB time in prolonged sedentary bouts (≥30 min) compared to blue-collar workers. During leisure time, the SB, LPA, and MVPA times were similar between the groups. White-collar workers have significantly longer SB times than blue-collar workers during work hours, and do not compensate for their excess SB during work by reducing SB during leisure time.

Ultrastrong light fields (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 29 October 2014)

NASA Astrophysics Data System (ADS)

2015-01-01

On 29 October 2014, the scientific session "Super strong light fields" of the Physical Sciences Division (PSD), Russian Academy of Sciences (RAS), was held at the conference hall of the Lebedev Physical Institute, RAS.The agenda of the session announced on the website http://www.gpad.ac.ru of the PSD RAS contains the reports: (1) Bychenkov V Yu (Lebedev Physical Institute, RAS, Moscow) "Laser acceleration of ions: New results and prospects for applications"; (2) Kostyukov I Yu (Institute of Applied Physics, RAS, Nizhnii Novgorod) "Plasma methods for electron acceleration: the state of the art and outlook"; (3) Zheltikov A M (Lomonosov Moscow State University, Moscow) "Nonlinear optics of mid-IR ultrashort pulses"; (4) Narozhnyi N B, Fedotov A M (Moscow Engineering Physics Institute, Nuclear Research University, Moscow) "Quantum electrodynamics cascades in intense laser fields."Papers written on the basis of oral presentations 1-4 are published below. • Laser acceleration of ions: recent results and prospects for applications, V Yu Bychenkov, A V Brantov, E A Govras, V F Kovalev Physics-Uspekhi, 2015, Volume 58, Number 1, Pages 71-81 • Plasma-based methods for electron acceleration: current status and prospects, I Yu Kostyukov, A M Pukhov Physics-Uspekhi, 2015, Volume 58, Number 1, Pages 81-88 • Subterawatt femtosecond pulses in the mid-infrared range: new spatiotemporal dynamics of high-power electromagnetic fields, A V Mitrofanov, D A Sidorov-Biryukov, A A Voronin, A Pugžlys, G Andriukaitis, E A Stepanov, S Ališauskas, T Flöri, A B Fedotov, V Ya Panchenko, A Baltuška, A M Zheltikov Physics-Uspekhi, 2015, Volume 58, Number 1, Pages 89-94 • Quantum-electrodynamic cascades in intense laser fields, N B Narozhny, A M Fedotov Physics-Uspekhi, 2015, Volume 58, Number 1, Pages 95-102

Characterization of basic physical properties of Sb 2Se 3 and its relevance for photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chao; Bobela, David C.; Yang, Ye

Antimony selenide (Sb 2Se 3) is a promising absorber material for thin film photovoltaics because of its attractive material, optical and electrical properties. In recent years, the power conversion efficiency (PCE) of Sb 2Se 3 thin film solar cells has gradually enhanced to 5.6%. In this article, we systematically studied the basic physical properties of Sb 2Se 3 such as dielectric constant, anisotropic mobility, carrier lifetime, diffusion length, defect depth, defect density and optical band tail states. Here, we believe such a comprehensive characterization of the basic physical properties of Sb 2Se 3 lays a solid foundation for further optimizationmore » of solar device performance.« less

Characterization of basic physical properties of Sb 2Se 3 and its relevance for photovoltaics

DOE PAGES

Chen, Chao; Bobela, David C.; Yang, Ye; ...

2017-03-17

Antimony selenide (Sb 2Se 3) is a promising absorber material for thin film photovoltaics because of its attractive material, optical and electrical properties. In recent years, the power conversion efficiency (PCE) of Sb 2Se 3 thin film solar cells has gradually enhanced to 5.6%. In this article, we systematically studied the basic physical properties of Sb 2Se 3 such as dielectric constant, anisotropic mobility, carrier lifetime, diffusion length, defect depth, defect density and optical band tail states. Here, we believe such a comprehensive characterization of the basic physical properties of Sb 2Se 3 lays a solid foundation for further optimizationmore » of solar device performance.« less

Isotemporal Substitution of Sedentary Behavior and Physical Activity on Function.

PubMed

Lerma, Nicholas L; Cho, Chi C; Swartz, Ann M; Miller, Nora E; Keenan, Kevin G; Strath, Scott J

2018-04-01

The amount of time spent in sedentary behaviors (SB) progressively increases with age, while reducing time spent in light-intensity physical activity (LPA) and moderate- to vigorous-intensity physical activity (MVPA). These trajectories in PA and SB are linked to accelerated reductions in physical functioning. This study aimed to examine the association of substituting SB time with LPA and MVPA on physical function in older adults. Ninety-one older adults (mean age, 70.7 ± 10.2 yr) wore a hip-mounted accelerometer to measure SB, LPA, and MVPA time. Measures of physical function included a 400-m walk test (400W), the usual gait speed (UGS), the five times sit-to-stand (5xSTS) test, and the short physical performance battery (SPPB). Isotemporal substitution regression modeling was performed to assess the relationship of replacing the amount of time spent in one activity for another. Replacing 30 min·d of SB with LPA was associated with a significant improvement in 400W (P = 0.0497), whereas MVPA resulted in a significant improvement (P < 0.01) in 400W, UGS, 5xSTS, and SPPB. Replacing 60 min·d of SB with 10 min·d of MVPA and 50 min·d of LPA was associated with significant improvements in the 400W, UGS, and 5xSTS (P < 0.05). Meanwhile, as little as 5 min·d of MVPA and 55 min·d of LPA were linked to a 78% increased odds of scoring with good function in the SPPB (P = 0.0247). Replacing SB with LPA was linked to a significant improvement in the 400W, but not the other brief functional measures. Mixed doses of LPA and MVPA may add flexibility to interventions targeting reductions of SB in older adults for clinically relevant improvements in physical function.

100th anniversary of the birth of I Ya Pomeranchuk (Extended session of the all-institute seminar at the Alikhanov Institute for Theoretical and Experimental Physics, 5 - 6 June 2013)

NASA Astrophysics Data System (ADS)

2014-02-01

On 5 - 6 June 2013, an extended session of the all-institute seminar was held at the Russian Federation State Scientific Center 'Alikhanov Institute for Theoretical and Experimental Physics' (ITEP). It was devoted to the 100th anniversary of the birth of Academician Isaak Yakovlevich Pomeranchuk, the founder of the Theory Department of ITEP. The announced agenda of the session on the ITEP website http://www.itep.ru/rus/Pomeranchuk100.html contained the following reports: (1) Gershtein S S (SRC 'Institute for High Energy Physics', Protvino, Moscow region) "I Ya Pomeranchuk and the large accelerator";(2) Keldysh L V (Lebedev Physical Institute, RAS (FIAN), Moscow) "Dynamic tunneling";(3) Vaks V G (National Research Centre 'Kurchatov Institute' (NRC KI), Moscow) "Brief reminiscences";(4) Smilga A V (Laboratoire Physique Subatomique et des technologies associées, Université de Nantes, France) "Vacuum structure in 3D supersymmetric gauge theories";(5) Khriplovich I B (Budker Institute of Nuclear Physics, SB RAS, Novosibirsk) "Gravitational four-fermion interaction and early Universe dynamics";(6) Dremin I M (FIAN, Moscow) "Elastic scattering of hadrons";(7) Belavin A A (Landau Institute of Theoretical Physics, RAS, Moscow) "Correlators in minimal string models";(8) Voloshin M B (Theoretical Physics Institute, University of Minnesota, USA) "Exotic quarkonium";(9) Nekrasov N A (Institut des hautes études scientifiques (IHES), France) "BPS/CFT correspondence";(10) Zarembo K (Uppsala Universitet, Sweden) "Exact results in supersymmetric theories and AdS/CFT correspondence";(11) Gorsky A S (ITEP, Moscow) "Baryon as a dyon instanton";(12) Blinnikov S I (ITEP, Moscow) "Mirror substance and other models for dark matter";(13) Rubakov V A (Institute for Nuclear Research, RAS, Moscow) "Test-tube Universe";(14) Kancheli O V (ITEP, Moscow) "50 years of reggistics";(15) Shevchenko V I (NRC KI) "In search of the chiral magnetic effect";(16) Kirilin V P (ITEP, Moscow) "Anomalies and long-range action";(17) Narozhny N B (National Research Nuclear University 'MEPhI', Moscow) "Superpower lasers as instruments for studying the properties of vacuum";(18) Kerbikov B O (ITEP, Moscow) "Hadrons in strong magnetic fields";(19) Neznamov V P, Safronov I I (Russian Federal Nuclear Center - All-Russian Scientific Research Institute of Experimental Physics (VNIIEF), Sarov, Nizhny Novgorod region) "A new method for solving the 'Z > 137' problem and determining hydrogen-like energy levels";(20) Vysotsky M I, Godunov S I (ITEP, Moscow) "Critical charge in a superstrong magnetic field";(21) Dolgov A D (Universitè degli Studi di Ferrara, Italy) "Cosmology: from Pomeranchuk to the present day".Papers written around the reports Nos 4, 5, 11, 12, 19 - 21 are published below. The content of report 6 in an extended form is reflected in I M Dremin's 2013 review of the same title published in Phys. Usp. 56 3 (2013). An extended version of report 13 is published in the present issue of Phys. Usp. 57 128 (2014). • Vacuum structure in 3D supersymmetric gauge theories, A V Smilga Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 155-166 • Gravitational four-fermion interaction in the early Universe, A S Rudenko, I B Khriplovich Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 167-170 • Limit cycles in renormalization group dynamics, K M Bulycheva, A S Gorsky Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 171-182 • Mirror matter and other dark matter models, S I Blinnikov Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 183-188 • New method for solving the Z>137 problem and determining hydrogen-like energy levels, V P Neznamov, I I Safronov Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 189-193 • Critical charge in a superstrong magnetic field, M I Vysotskii, S I Godunov Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 194-198 • Cosmology: from Pomeranchuk to the present day, A D Dolgov Physics-Uspekhi, 2014, Volume 57, Number 2, Pages 199-208

Sedentary and Physical Activity Habits of Obese Adolescents

ERIC Educational Resources Information Center

Starkoff, Brooke E.; Petosa, Rick L.; Balk, Elizabeth K.; Eneli, Ihuoma U.; Bonny, Andrea E.; Hoffman, Robert P.; Devor, Steven T.

2014-01-01

Background: The independent association between sedentary behavior (SB) and physical activity (PA) is such that, regardless of accumulated PA, high amounts of SB are detrimental to health, even in adolescents. Purpose: Our aim was to profile activity patterns in free-living environments and to measure levels of SB and light (LT) and moderate (MOD)…

Effect of Retraining Approach-Avoidance Tendencies on an Exercise Task: A Randomized Controlled Trial.

PubMed

Cheval, Boris; Sarrazin, Philippe; Pelletier, Luc; Friese, Malte

2016-12-01

Promoting regular physical activity (PA) and lessening sedentary behaviors (SB) constitute a public health priority. Recent evidence suggests that PA and SB are not only related to reflective processes (eg, behavioral intentions), but also to impulsive approach-avoidance tendencies (IAAT). This study aims to test the effect of a computerized IAAT intervention on an exercise task. Participants (N = 115) were randomly assigned to 1 of 3 experimental conditions, in which they were either trained to approach PA and avoid SB (ApPA-AvSB condition), to approach SB and avoid PA (ApSB-AvPA condition), or to approach and avoid PA and SB equally often (active control condition). The main outcome variable was the time spent carrying out a moderate intensity exercise task. IAAT toward PA decreased in the ApSB-AvPA condition, tended to increase in the ApPA-AvSB condition, and remained stable in the control condition. Most importantly, the ApPA-AvSB manipulation led to more time spent exercising than the ApSB-AvPA condition. Sensitivity analyses excluding individuals who were highly physically active further revealed that participants in the ApPA-AvSB condition spent more time exercising than participants in the control condition. These findings provide preliminary evidence that a single intervention session can successfully change impulsive approach tendencies toward PA and can increase the time devoted to an exercise task, especially among individuals who need to be more physically active. Potential implications for health behavior theories and behavior change interventions are outlined.

Objectively measured sedentary behavior and moderate-to-vigorous physical activity on the health-related quality of life in US adults: The National Health and Nutrition Examination Survey 2003-2006.

PubMed

Kim, Junghoon; Im, Jeong-Soo; Choi, Yoon-Hyeong

2017-05-01

Health-related quality of life (HRQOL) represents an individual's perception of physical, mental, and social well-being and is a strong predictor of health status. Few studies have examined associations of sedentary behavior (SB) and moderate-to-vigorous physical activity (MVPA) with HRQOL in the general population. This study aimed to determine combined associations of objectively measured SB and MVPA on the risk of poor HRQOL in the general US population, after controlling for potential confounding factors. We analyzed data from 5359 adults from the National Health and Nutrition Examination Survey 2003-2006. HRQOL was measured using a HRQOL-4 consisting of four questions focused on the self-perception of general health, physical health, mental health, and activity limitation. We dichotomized each HRQOL-4 component as good versus poor and defined poor overall HRQOL when participants had any poor HRQOL components. SB and MVPA were measured using an accelerometer. Survey logistic models were examined to estimate the odds ratio (OR) and 95% confidence interval (CI) for poor HRQOL by SB and MVPA as tertiles. When examined as a combination of SB and MVPA, a substantial decrease in the risk of poor overall HRQOL was found in individuals with low SB/high MVPA [OR 0.69 (95% CI 0.51-0.94) and moderate SB/high MVPA (OR 0.56 (95% CI 0.40-0.78)], but no significant decrease was found in individuals with high SB/high MVPA (vs. high SB/low MVPA). Our findings suggest that both increasing MVPA and reducing time spent in SB may be useful strategies to improve HRQOL.

Joint effect of physical activity and sedentary behaviour on cardiovascular risk factors in Chilean adults.

PubMed

Cristi-Montero, Carlos; Steell, Lewis; Petermann, Fanny; Garrido-Méndez, Alex; Díaz-Martínez, Ximena; Salas-Bravo, Carlos; Ramirez-Campillo, Rodrigo; Alvarez, Cristian; Rodriguez, Fernando; Aguilar-Farias, Nicolas; Martinez, Maria A; Leiva, Ana M; Poblete-Valderrama, Felipe; Willis, Naomi D; Celis-Morales, Carlos A

2017-10-17

To investigate the associations between combined categories of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) with markers of adiposity and cardiovascular risk in adults. Overall, 5040 participants (mean age 46.4 years and 59.3% women) from the cross-sectional Chilean National Health Survey 2009-2010 were included in this study. MVPA and SB were measured using the Global Physical Activity questionnaire. Four categories were computed using MVPA- and SB-specific cut-offs ('High-SB & Active', 'Low-SB & Active', 'High-SB & Inactive' and 'Low-SB & Inactive'). Compared to the reference group ('High-SB & Inactive'), those in 'High-SB & Active' and 'Low-SB & Active' were less likely to have an obese BMI (OR: 0.67 [0.54; 0.85], P = 0.0001 and 0.74 [0.59; 0.92] P = 0.0007, respectively) and less likely to have metabolic syndrome (OR: 0.63 [0.49; 0.82], P < 0.0001 and 0.72 [0.57; 0.91], P = 0.007), central obesity (OR: 0.79 [0.65; 0.96], P = 0.016 and 0.71 [0.59; 0.84], P < 0.0001), diabetes (OR: 0.45 [0.35; 0.59], P < 0.0001 and 0.44 [0.34; 0.56], P < 0.0001) and hypertension (OR: 0.52 [0.43; 0.63], P < 0.0001 and 0.60 [0.50; 0.72], P < 0.0001), respectively. Being physically active and spending less time in SBs was associated with lower adiposity and improvements in cardiovascular risk factors. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Synchronized personalized music audio-playlists to improve adherence to physical activity among patients participating in a structured exercise program: a proof-of-principle feasibility study.

PubMed

Alter, David A; O'Sullivan, Mary; Oh, Paul I; Redelmeier, Donald A; Marzolini, Susan; Liu, Richard; Forhan, Mary; Silver, Michael; Goodman, Jack M; Bartel, Lee R

2015-01-01

Preference-based tempo-pace synchronized music has been shown to reduce perceived physical activity exertion and improve exercise performance. The extent to which such strategies can improve adherence to physical activity remains unknown. The objective of the study is to explore the feasibility and efficacy of tempo-pace synchronized preference-based music audio-playlists on adherence to physical activity among cardiovascular disease patients participating in a cardiac rehabilitation. Thirty-four cardiac rehabilitation patients were randomly allocated to one of two strategies: (1) no music usual-care control and (2) tempo-pace synchronized audio-devices with personalized music playlists + usual-care. All songs uploaded onto audio-playlist devices took into account patient personal music genre and artist preferences. However, actual song selection was restricted to music whose tempos approximated patients' prescribed exercise walking/running pace (steps per minute) to achieve tempo-pace synchrony. Patients allocated to audio-music playlists underwent further randomization in which half of the patients received songs that were sonically enhanced with rhythmic auditory stimulation (RAS) to accentuate tempo-pace synchrony, whereas the other half did not. RAS was achieved through blinded rhythmic sonic-enhancements undertaken manually to songs within individuals' music playlists. The primary outcome consisted of the weekly volume of physical activity undertaken over 3 months as determined by tri-axial accelerometers. Statistical methods employed an intention to treat and repeated-measures design. Patients randomized to personalized audio-playlists with tempo-pace synchrony achieved higher weekly volumes of physical activity than did their non-music usual-care comparators (475.6 min vs. 370.2 min, P  < 0.001). Improvements in weekly physical activity volumes among audio-playlist recipients were driven by those randomized to the RAS group which attained weekly exercise volumes that were nearly twofold greater than either of the two other groups (average weekly minutes of physical activity of 631.3 min vs. 320 min vs. 370.2 min, personalized audio-playlists with RAS vs. personalized audio-playlists without RAS vs. non-music usual-care controls, respectively, P  < 0.001). Patients randomized to music with RAS utilized their audio-playlist devices more frequently than did non-RAS music counterparts ( P  < 0.001). The use of tempo-pace synchronized preference-based audio-playlists was feasibly implemented into a structured exercise program and efficacious in improving adherence to physical activity beyond the evidence-based non-music usual standard of care. Larger clinical trials are required to validate these findings. ClinicalTrials.gov ID (NCT01752595).

Adolescents' Physical Activity and Sedentary Behavior: A Pathway in Reducing Overweight and Obesity. The PRALIMAP 2-Year Cluster Randomized Controlled Trial.

PubMed

Omorou, Abdou Y; Langlois, Johanne; Lecomte, Edith; Vuillemin, Anne; Briançon, Serge

2015-05-01

explaining why and how overweight prevention programs were effective was a real need; especially the potential role of physical activity (PA) and sedentary behavior (SB) should be highlighted. This study aimed to evaluate the 2-year effectiveness of a screening and care strategy in adolescents' weight reduction with regards to PA and SB change. 1745 adolescents aged 15.1 years from PRALIMAP trial was included (n = 840 for screening and care group and n = 905 for control group). PA and SB time (international physical activity questionnaire: IPAQ), body mass index (BMI), and BMI z-score were assessed at inclusion and after 2-year intervention. Hierarchical mixed models were applied. Compared with the control group, screening and care strategy was associated with an increase in global PA (58 min/week), a moderate PA (43 min/week), the adherence to the French PA guidelines (OR = 1.3), and a decrease in SB (-198 min/week). The 2-year weight change decreased when adjusted for PA and SB suggesting that the effect of screening and care strategy was partly mediated by PA and SB. Screening and care intervention seemed to be effective in increasing PA and decreasing SB. The induced PA and SB modifications contributed to the observed weight change.

PREFACE: IV Nanotechnology International Forum (RUSNANOTECH 2011)

NASA Astrophysics Data System (ADS)

Dvurechenskii, Anatoly; Alfimov, Mikhail; Suzdalev, Igor; Osiko, Vyacheslav; Khokhlov, Aleksey; Son, Eduard; Skryabin, Konstantin; Petrov, Rem; Deev, Sergey

2012-02-01

Logo The RUSNANOTECH 2011 International Forum on Nanotechnology was held from 26-28 October 2011, in Moscow, Russia. It was the fourth forum organized by RUSNANO (Russian Corporation of Nanotechnologies) since 2008. In March 2011 RUSNANO was established as an open joint-stock company through the reorganization of the state corporation Russian Corporation of Nanotechnologies. RUSNANO's mission is to develop the Russian nanotechnology industry through co-investment in nanotechnology projects with substantial economic potential or social benefit. Within the framework of the Forum Science and Technology Program, presentations on key trends of nanotechnology development were given by foreign and Russian scientists, R&D officers of leading international companies, universities and scientific centers. The science and technology program of the Forum was divided into four sections as follows (by following hyperlinks you may find each section's program including videos of all oral presentations): Nanoelectronics and Nanophotonics Nanomaterials Nanotechnology and Green Energy Nanotechnology in Healthcare and Pharma (United business and science & technology section on 'RUSNANOTECH 2011') The scientific program of the forum included more than 50 oral presentations by leading scientists from 15 countries. Among them were world-known specialists such as Professor S Bader (Argonne National Laboratory, USA), Professor O Farokzhad (Harvard Medical School, USA), Professor K Chien (Massachusetts General Hospital, USA), Professor L Liz-Marzan (University of Vigo), A Luque (Polytechnic University of Madrid) and many others. The poster session consisted of over 120 presentations, 90 of which were presented in the framework of the young scientists' nanotechnology papers competition. This volume of Journal of Physics: Conference Series includes a selection of 47 submissions. Section editors of the proceedings: Nanoelectronics and nanophotonics Corresponding Member of Russian Academy of Sciences, Professor Anatoly Dvurechenskii (Institute of Semiconductor Physics, RAS). Nanomaterials Member of Russian Academy of Sciences, Professor Mikhail Alfimov (Photochemistry Center, RAS), Professor Igor Suzdalev (Semenov Institute of Chemical Physics, RAS), Member of Russian Academy of Science, Professor Vyacheslav Osiko (Prokhorov General Physics Institute, RAS), Member of Russian Academy of Science, Professor Aleksey Khokhlov (Physical department of Moscow State University). Nanotechnology and green energy Corresponding Member of Russian Academy of Sciences, Professor Eduard Son (Joint Institute for High Temperatures, RAS). Nanotechnology in Healthcare and Pharma Member of Russian Academy of Sciences, Professor Konstantin Skryabin (Bioengineering Center, RAS), Member of Russian Academy of Sciences, Professor Rem Petrov (RAS), Corresponding Member of Russian Academy of Sciences, Professor Sergey Deev (Institute of Bioorganic Chemistry).

Physical Model Study of Cross Vanes and Ice

DTIC Science & Technology

2009-08-01

spacing since, in the pre-scour state, experiments and the HEC - RAS hydraulic model (USACE 2002b) found that water surface ele- vation merged with the...docs/eng-manuals/em1110- 2-1612/toc.htm. USACE (2002b) HEC - RAS , Hydraulic Reference Manual. US Army Corps of Engineers Hydrologic Engineering Center...Currently little design guidance is available for constructing these structures on ice-affected rivers . This study used physical and numerical

Dynamic correction of the laser beam coordinate in fabrication of large-sized diffractive elements for testing aspherical mirrors

NASA Astrophysics Data System (ADS)

Shimansky, R. V.; Poleshchuk, A. G.; Korolkov, V. P.; Cherkashin, V. V.

2017-05-01

This paper presents a method of improving the accuracy of a circular laser system in fabrication of large-diameter diffractive optical elements by means of a polar coordinate system and the results of their use. An algorithm for correcting positioning errors of a circular laser writing system developed at the Institute of Automation and Electrometry, SB RAS, is proposed and tested. Highprecision synthesized holograms fabricated by this method and the results of using these elements for testing the 6.5 m diameter aspheric mirror of the James Webb space telescope (JWST) are described..

Combined Effects of Time Spent in Physical Activity, Sedentary Behaviors and Sleep on Obesity and Cardio-Metabolic Health Markers: A Novel Compositional Data Analysis Approach

PubMed Central

Chastin, Sebastien F. M.; Palarea-Albaladejo, Javier; Dontje, Manon L.; Skelton, Dawn A.

2015-01-01

The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity. PMID:26461112

Schoolyard Characteristics, Physical Activity, and Sedentary Behavior: Combining GPS and Accelerometry

ERIC Educational Resources Information Center

Van Kann, Dave H. H.; de Vries, Sanne I.; Schipperijn, Jasper; de Vries, Nanne K.; Jansen, Maria W. J.; Kremers, Stef P. J.

2016-01-01

Background: Physical activity (PA) is decreasing among children, while sedentary behavior (SB) is increasing. Schoolyards seem suitable settings to influence children's PA behavior. This study investigated the associations between schoolyard characteristics and moderate-to-vigorous physical activity (MVPA) and SB of children aged 8-11 years at…

A review of the assessment and prevalence of sedentarism in older adults, its physiology/health impact and non-exercise mobility counter-measures.

PubMed

Wullems, Jorgen A; Verschueren, Sabine M P; Degens, Hans; Morse, Christopher I; Onambélé, Gladys L

2016-06-01

This literature review focuses on aspects of sedentary behaviour (SB) in elderly. Since it has been identified as a distinct health risk, independent of physical activity, SB is a significant issue. This is particularly true for an ageing population as evidence shows that older adults (aged ≥65 years) are the most sedentary age group (on average 8.5-9.6 h daily sitting time). Accurate SB assessment is important for understanding this habitual behaviour and its impact. However, SB measurement is challenging, regardless of the method used. Although negative associations of SB in elderly have been reported for several health outcomes, evidence is inconclusive, apart from the evidence on the adverse SB effect on the all-cause mortality rate. Generally, strategies have been proposed to counteract SB, of which breaking prolonged sedentary bouts with at least light-intensity physical activity seems to be the most promising. Overall, further research in elderly is required to increase the evidence and to either support or refute the current findings. Moreover, further research will help to develop informed SB guidelines for an optimal strategy to counteract SB and its health effects in older adults.

Mediated Effects of Perceived Competence on Youth Physical Activity and Sedentary Behavior.

PubMed

Bai, Yang; Chen, Senlin; Vazou, Spyridoula; Welk, Gregory J; Schaben, Jodee

2015-01-01

This study evaluates whether physical activity (PA) and sedentary behavior (SB) are influenced by a common mediating relationship. A total of 1,552 participants in 3rd to 12th grade completed an online survey that included assessments of PA at school (PAS), PA at home (PAH), and SB as well as a battery of psychosocial variables (i.e., attraction to PA and perceived competence). Perceived competence had a direct positive effect on PA and a negative effect on SB. These associations were consistently (but partially) mediated by attraction to PA; however, the indirect effect (IE) of perceived competence was stronger for PAH (IE = .27, p < .05) than for PAS (IE = .07, p < .05), or SB (IE = .13, p < .05). This study revealed some direct effects and IEs of perceived competence on PAS, PAH, and SB through attraction to PA as the mediator. PA and SB may be influenced by some common underlying psychosocial mediators.

CONFERENCES AND SYMPOSIA: Commemoration of the centenary of the birth of Academician L A Artsimovich(Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 18 February 2009; Joint session of the Research Council of the Russian Research Centre 'Kurchatov Institute', the Presidium of the Russian Academy of Sciences, and the Rosatom State Corporation, 18 March 2009)

NASA Astrophysics Data System (ADS)

Khalatnikov, Isaak M.; Fortov, Vladimir E.; Makarov, Aleksandr A.; Fridman, Aleksei M.; Martynenko, Yurii V.

2009-12-01

The scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) devoted to the centenary of the birth of Academician L A Artsimovich was held on 18 February 2009 in the conference hall of the P N Lebedev Physical Institute, RAS. The following reports were presented at the session: (1) Khalatnikov I M (L D Landau Institute of Theoretical Physics, RAS, Chernogolovka, Moscow region) "Nonaccidental coincidences (Lev Andreevich Artsimovich)"; (2) Pashinin P P (A M Prokhorov Institute of General Physics, RAS, Moscow) "L A Artsimovich and inertial thermonuclear fusion"; (3) Fortov V E (Institute of Thermophysics of Extreme States of the Joint Institute for High Temperatures, RAS, Moscow) "High-power shock waves and extreme states of plasma"; (4) Fridman A M (Institute of Astronomy, RAS, Moscow) "Prediction and discovery of ultrastrong hydrodynamic instabilities caused by a velocity jump: theory and experiment"; (5) Smirnov V P (Russian Research Centre 'Kurchatov Institute', Moscow) "Retracing Artsimovich's path to the thermonuclear source of energy". On 18 March 2009, a joint session of the Learned Council of the Russian Research Centre 'Kurchatov Institute' (RNTsKI in Russ. abbr.), the Presidium of the Russian Academy of Sciences, and the Rosatom State Corporation took place at RNTsKI; the session was devoted to the 100th anniversary of the birth of Academician L A Artsimovich. The following talks were presented at the session: (1) Velikhov E P (Russian Research Centre 'Kurchatov Institute', Moscow) "Academician L A Artsimovich—the founder of our field of science and industry"; (2) Smirnov V P (Russian Research Centre 'Kurchatov Institute', Moscow) "Retracing Artsimovich's path to the thermonuclear source of energy"; (3) Boyarchuk A A (Division of General Physics and Astronomy, RAS, Moscow) "L A Artsimovich and astronomy"; (4) Martynenko Yu V (Institute of Nuclear Fusion, Russian Research Centre 'Kurchatov Institute', Moscow) "Electromagnetic isotope separation method and its heritage"; (5) Strelkov V S (Institute of Nuclear Fusion, Russian Research Centre 'Kurchatov Institute', Moscow) "Our teacher: Lev Andreevich Artsimovich"; (6) Mirnov S V (Institute of Nuclear Fusion, Russian Research Centre 'Kurchatov Institute', Moscow) "L A Artsimovich through the eyes of a former postgraduate student". • Nonaccidental coincidences (Lev Andreevich Artsimovich), I M Khalatnikov Physics-Uspekhi, 2009, Volume 52, Number 12, Pages 1248-1249 • Avenues for the innovative development of energetics in the world and in Russia, V E Fortov, A A Makarov Physics-Uspekhi, 2009, Volume 52, Number 12, Pages 1249-1265 • Lev Andreevich Artsimovich and extremely strong hydrodynamic instabilities, A M Fridman Physics-Uspekhi, 2009, Volume 52, Number 12, Pages 1265-1266 • Electromagnetic isotope separation method and its heritage, Yu V Martynenko Physics-Uspekhi, 2009, Volume 52, Number 12, Pages 1266-1272

100th anniversary of the birth of B M Pontecorvo (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 2 September 2013)

NASA Astrophysics Data System (ADS)

2014-05-01

A scientific session "Prospects of Studies in Neutrino Particle Physics and Astrophysics," of the Physical Sciences Division of the Russian Academy of Sciences (DPS RAS), devoted to the centenary of B M Pontecorvo, was held on 2-3 September 2014 at the JINR international conference hall (Dubna, Moscow region).The following reports were put on the session agenda as posted on the website http://www.gpad.ac.ru of the RAS Physical Sciences Division: (1) Kudenko Yu G (Institute for Nuclear Research, RAS, Moscow; Moscow Institute of Physics and Technology, Dolgoprudnyi, Moscow region; National Research Nuclear University MEPhI, Moscow) "Long-baseline neutrino accelerator experiments: results and prospects";(2) Spiering Ch (Deutsches Elektronen-Synchrotron (DESY), Germany) "Results obtained by ICECUBE and prospects of neutrino astronomy";(3) Barabash A S (Alikhanov Institute for Theoretical and Experimental Physics, Moscow) "Double beta decay experiments: current status and prospects";(4) Bilenky S M (Joint Institute for Nuclear Research, Dubna, Moscow region; Technische Universitat M'unchen, Garching, Germany) "Bruno Pontecorvo and the neutrino";(5) Olshevskiy A G (Joint Institute for Nuclear Research, Dubna, Moscow region) "Reactor neutrino experiments: results and prospects";(6) Gavrin V N (Institute for Nuclear Research, RAS, Moscow) "Low-energy neutrino research at the Baksan Neutrino Laboratory";(7) Gorbunov D S (Institute for Nuclear Research, RAS, Moscow): "Sterile neutrinos and their role in particle physics and cosmology";(8) Derbin A V (Konstantinov Petersburg Nuclear Physics Institute, Gatchina, Leningrad region) "Solar neutrino experiments";(9) Rubakov V A (Institute for Nuclear Research, RAS, Moscow) "Prospects of studies in the field of neutrino particle physics and astrophysics." An article by V N Gavrin, close in essence to talk 6, was published in Usp. Fiz. Nauk 181 (9), 975 (2011) [Phys. Usp. 54 (9) 941 (2011)]. Articles by V A Rubakov, close in essence to talk 9, were published in Usp. Fiz. Nauk 182 (10) 1017 (2012); 181 (6) 655 (2011) [Phys. Usp. 55 (10) 949 (2012); 54 (6) 633 (2011)]. Articles based on talks 1-5, 7, and 8 are published below. • Long-baseline neutrino accelerator experiments: results and prospects, Yu G Kudenko Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 462-469 • High-energy neutrino astronomy: a glimpse of the promised land, Ch Spiering Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 470-481 • Double beta decay experiments: current status and prospects, A S Barabash Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 482-488 • Bruno Pontecorvo and the neutrino, S M Bilenky Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 489-496 • Reactor neutrino experiments: results and prospects, A G Olshevskiy Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 497-502 • Sterile neutrinos and their role in particle physics and cosmology, D S Gorbunov Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 503-511 • Solar neutrino experiments, A V Derbin Physics-Uspekhi, 2014, Volume 57, Number 5, Pages 512-524

Hands-on approach to teaching Earth system sciences using a information-computational web-GIS portal "Climate"

NASA Astrophysics Data System (ADS)

Gordova, Yulia; Gorbatenko, Valentina; Martynova, Yulia; Shulgina, Tamara

2014-05-01

A problem of making education relevant to the workplace tasks is a key problem of higher education because old-school training programs are not keeping pace with the rapidly changing situation in the professional field of environmental sciences. A joint group of specialists from Tomsk State University and Siberian center for Environmental research and Training/IMCES SB RAS developed several new courses for students of "Climatology" and "Meteorology" specialties, which comprises theoretical knowledge from up-to-date environmental sciences with practical tasks. To organize the educational process we use an open-source course management system Moodle (www.moodle.org). It gave us an opportunity to combine text and multimedia in a theoretical part of educational courses. The hands-on approach is realized through development of innovative trainings which are performed within the information-computational platform "Climate" (http://climate.scert.ru/) using web GIS tools. These trainings contain practical tasks on climate modeling and climate changes assessment and analysis and should be performed using typical tools which are usually used by scientists performing such kind of research. Thus, students are engaged in n the use of modern tools of the geophysical data analysis and it cultivates dynamic of their professional learning. The hands-on approach can help us to fill in this gap because it is the only approach that offers experience, increases students involvement, advance the use of modern information and communication tools. The courses are implemented at Tomsk State University and help forming modern curriculum in Earth system science area. This work is partially supported by SB RAS project VIII.80.2.1, RFBR grants numbers 13-05-12034 and 14-05-00502.

Physical activity: from epidemiological evidence to individualized patient management.

PubMed

Charansonney, Olivier Luc; Vanhees, Luc; Cohen-Solal, Alain

2014-01-01

Physical activity (PA), physical fitness (PF), and even a few sedentary behaviors (SB) are strongly and independently linked to improved survival rate. However, key questions remain: what are the physiological interrelationships between SB, PA, and PF? How should we differently emphasize promoting PA, increasing PF with exercise, and decreasing SB among other prevention measures? What are the interrelationships of both PA and SB levels with drug treatment efficacy? To address these questions we developed an integrated patient-centric model combining physiology with epidemiological evidence to characterize the individual risk attached to PA level, PF, and SB. Epidemiological data were collected by extensive literature review. Nine meta-analyses, 198 cohort studies (3.8 million people), and 13 controlled trials were reviewed. 1. A high level of SB induces chronic stress and increases the risk of both chronic disease and mortality. 2. Vigorous PA increases PF and physiological reserve, thereby improving survival rate. This effect is not mediated by improved traditional risk factors. The risk for most individuals is a mix of high SB, low to mild PA, and low to mild PF. This model can improve the individualized prescription of PA modalities. Furthermore, the benefit of treatments such as statins or beta-blockers can be cancelled out if a decrease in PA or an increase in SB is induced by drug related side effects. To improve patient management both types of therapeutic interventions and dose should be carefully chosen for each individual in order to maintain/increase PA level while decreasing SB. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impacts of active school design on school-time sedentary behavior and physical activity: A pilot natural experiment.

PubMed

Brittin, Jeri; Frerichs, Leah; Sirard, John R; Wells, Nancy M; Myers, Beth M; Garcia, Jeanette; Sorensen, Dina; Trowbridge, Matthew J; Huang, Terry

2017-01-01

Children spend a significant portion of their days in sedentary behavior (SB) and on average fail to engage in adequate physical activity (PA). The school built environment may influence SB and PA, but research is limited. This natural experiment evaluated whether an elementary school designed to promote movement impacted students' school-time SB and PA. Accelerometers measured SB and PA at pre and post time-points in an intervention group who moved to the new school (n = 21) and in a comparison group experiencing no school environmental change (n = 20). Difference-in-difference (DD) analysis examined SB and PA outcomes in these groups. Measures were also collected post-intervention from an independent, grade-matched group of students in the new school (n = 21). As expected, maturational increases in SB were observed. However, DD analysis estimated that the intervention attenuated increase in SB by 81.2 ± 11.4 minutes/day (p<0.001), controlling for time in moderate to vigorous physical activity (MVPA). The intervention was also estimated to increase daily number of breaks from SB by 23.4 ± 2.6 (p < .001) and to increase light physical activity (LPA) by 67.7 ± 10.7 minutes/day (p<0.001). However, the intervention decreased MVPA by 10.3 ± 2.3 minutes/day (p<0.001). Results of grade-matched independent samples analysis were similar, with students in the new vs. old school spending 90.5 ± 16.1 fewer minutes/day in SB, taking 21.1 ± 2.7 more breaks from SB (p<0.001), and spending 64.5 ± 14.8 more minutes in LPA (p<0.001), controlling for time in MVPA. Students in the new school spent 13.1 ± 2.7 fewer minutes in MVPA (p<0.001) than their counterparts in the old school. This pilot study found that active school design had beneficial effects on SB and LPA, but not on MVPA. Mixed results point to a need for active classroom design strategies to mitigate SB, and quick access from classrooms to areas permissive of high-intensity activities to promote MVPA. Integrating active design with programs/policies to promote PA may yield greatest impact on PA of all intensities.

Impacts of active school design on school-time sedentary behavior and physical activity: A pilot natural experiment

PubMed Central

Frerichs, Leah; Sirard, John R.; Wells, Nancy M.; Myers, Beth M.; Garcia, Jeanette; Sorensen, Dina; Trowbridge, Matthew J.; Huang, Terry

2017-01-01

Background Children spend a significant portion of their days in sedentary behavior (SB) and on average fail to engage in adequate physical activity (PA). The school built environment may influence SB and PA, but research is limited. This natural experiment evaluated whether an elementary school designed to promote movement impacted students’ school-time SB and PA. Methods Accelerometers measured SB and PA at pre and post time-points in an intervention group who moved to the new school (n = 21) and in a comparison group experiencing no school environmental change (n = 20). Difference-in-difference (DD) analysis examined SB and PA outcomes in these groups. Measures were also collected post-intervention from an independent, grade-matched group of students in the new school (n = 21). Results As expected, maturational increases in SB were observed. However, DD analysis estimated that the intervention attenuated increase in SB by 81.2 ± 11.4 minutes/day (p<0.001), controlling for time in moderate to vigorous physical activity (MVPA). The intervention was also estimated to increase daily number of breaks from SB by 23.4 ± 2.6 (p < .001) and to increase light physical activity (LPA) by 67.7 ± 10.7 minutes/day (p<0.001). However, the intervention decreased MVPA by 10.3 ± 2.3 minutes/day (p<0.001). Results of grade-matched independent samples analysis were similar, with students in the new vs. old school spending 90.5 ± 16.1 fewer minutes/day in SB, taking 21.1 ± 2.7 more breaks from SB (p<0.001), and spending 64.5 ± 14.8 more minutes in LPA (p<0.001), controlling for time in MVPA. Students in the new school spent 13.1 ± 2.7 fewer minutes in MVPA (p<0.001) than their counterparts in the old school. Conclusions This pilot study found that active school design had beneficial effects on SB and LPA, but not on MVPA. Mixed results point to a need for active classroom design strategies to mitigate SB, and quick access from classrooms to areas permissive of high-intensity activities to promote MVPA. Integrating active design with programs/policies to promote PA may yield greatest impact on PA of all intensities. PMID:29216300

Synthesis, Structure, Te Alloying, and Physical Properties of CuSbS 2

DOE PAGES

Hobbis, Dean; Wei, Kaya; Wang, Hsin; ...

2017-10-30

Materials with very low thermal conductivities continue to be of interest for a variety of applications. In this paper, we synthesized CuSbS 2 employing a mechanical alloying technique in order to investigate its physical properties. The trigonal pyramid arrangement of the S atoms around the Sb atoms allows for lone-pair electron formation that results in very low thermal conductivity. Finally, in addition to thermal properties, the structural, electrical, and optical properties, as well as compositional stability measurements, are also discussed. CuSbS 1.8Te 0.2 was similarly synthesized and characterized in order to compare its structural and transport properties with that ofmore » CuSbS 2, in addition to investigating the effect of Te alloying on these properties.« less

Synthesis, Structure, Te Alloying, and Physical Properties of CuSbS 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hobbis, Dean; Wei, Kaya; Wang, Hsin

Materials with very low thermal conductivities continue to be of interest for a variety of applications. In this paper, we synthesized CuSbS 2 employing a mechanical alloying technique in order to investigate its physical properties. The trigonal pyramid arrangement of the S atoms around the Sb atoms allows for lone-pair electron formation that results in very low thermal conductivity. Finally, in addition to thermal properties, the structural, electrical, and optical properties, as well as compositional stability measurements, are also discussed. CuSbS 1.8Te 0.2 was similarly synthesized and characterized in order to compare its structural and transport properties with that ofmore » CuSbS 2, in addition to investigating the effect of Te alloying on these properties.« less

Decentralized State Estimation and Remedial Control Action for Minimum Wind Curtailment Using Distributed Computing Platform

DOE PAGES

Liu, Ren; Srivastava, Anurag K.; Bakken, David E.; ...

2017-08-17

Intermittency of wind energy poses a great challenge for power system operation and control. Wind curtailment might be necessary at the certain operating condition to keep the line flow within the limit. Remedial Action Scheme (RAS) offers quick control action mechanism to keep reliability and security of the power system operation with high wind energy integration. In this paper, a new RAS is developed to maximize the wind energy integration without compromising the security and reliability of the power system based on specific utility requirements. A new Distributed Linear State Estimation (DLSE) is also developed to provide the fast andmore » accurate input data for the proposed RAS. A distributed computational architecture is designed to guarantee the robustness of the cyber system to support RAS and DLSE implementation. The proposed RAS and DLSE is validated using the modified IEEE-118 Bus system. Simulation results demonstrate the satisfactory performance of the DLSE and the effectiveness of RAS. Real-time cyber-physical testbed has been utilized to validate the cyber-resiliency of the developed RAS against computational node failure.« less

Decentralized State Estimation and Remedial Control Action for Minimum Wind Curtailment Using Distributed Computing Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ren; Srivastava, Anurag K.; Bakken, David E.

Intermittency of wind energy poses a great challenge for power system operation and control. Wind curtailment might be necessary at the certain operating condition to keep the line flow within the limit. Remedial Action Scheme (RAS) offers quick control action mechanism to keep reliability and security of the power system operation with high wind energy integration. In this paper, a new RAS is developed to maximize the wind energy integration without compromising the security and reliability of the power system based on specific utility requirements. A new Distributed Linear State Estimation (DLSE) is also developed to provide the fast andmore » accurate input data for the proposed RAS. A distributed computational architecture is designed to guarantee the robustness of the cyber system to support RAS and DLSE implementation. The proposed RAS and DLSE is validated using the modified IEEE-118 Bus system. Simulation results demonstrate the satisfactory performance of the DLSE and the effectiveness of RAS. Real-time cyber-physical testbed has been utilized to validate the cyber-resiliency of the developed RAS against computational node failure.« less

The descriptive epidemiology of total physical activity, muscle-strengthening exercises and sedentary behaviour among Australian adults--results from the National Nutrition and Physical Activity Survey.

PubMed

Bennie, Jason A; Pedisic, Zeljko; van Uffelen, Jannique G Z; Gale, Joanne; Banting, Lauren K; Vergeer, Ineke; Stamatakis, Emmanuel; Bauman, Adrian E; Biddle, Stuart J H

2016-01-25

The current Australia's Physical Activity and Sedentary Behaviour Guidelines recommend that adults engage in regular moderate-to-vigorous-intensity physical activity (MVPA) and strength training (ST), and minimise time spent in sedentary behaviours (SB). However, evidence about the specific individual and concurrent distribution of these behaviours in Australia is scarce. Therefore, the aim of this study was to determine the prevalence and sociodemographic correlates of MVPA, ST and SB in a national-representative sample of Australian adults. Data were collected using face-to-face interviews, as part of the National Nutrition and Physical Activity Survey 2011-12. The population-weighted proportions meeting the MVPA (≥ 150 min/week), ST (≥ 2 sessions/week) and combined MVPA-ST guidelines, and proportions classified as having 'low levels of SB' (< 480 min/day) were calculated, and their associations with selected sociodemographic and health-related variables were assessed using multiple logistic regression analyses. This was also done for those at potentially 'high-risk', defined as insufficient MVPA-ST and 'high-sedentary' behaviour. Out of 9345 participants (response rate = 77.0 %), aged 18-85 years, 52.6 % (95 % CI: 51.2 %-54.0 %), 18.6 % (95 % CI: 17.5 %-19.7 %) and 15.0 % (95 % CI: 13.9 %-16.1 %) met the MVPA, ST and combined MVPA-ST guidelines, respectively. Female gender, older age, low/medium education, poorer self-rated health, being classified as underweight or obese, and being a current smoker were independently associated with lower odds of meeting the MVPA, ST and combined MVPA-ST guidelines. A total of 78.9 % (95 % CI: 77.9 %-80.0 %) were classified as having low levels of SB. Females, older adults and those with lower education were more likely to report lower levels of SB, whilst those with poor self-rated health and obese individuals were less likely to report lower levels of SB (i.e. SB = ≥ 480 min/day). A total of 8.9 % (95 % CI: 8.1 %-9.6 %) were categorised as individuals at potentially 'high-risk'. Those with poorer self-rated health, obese individuals, those aged 25-44, and current smokers were more likely to be in the 'high risk' group. The large majority of Australian adults do not meet the full physical activity guidelines and/or report excessive SB. Our results call for public health interventions to reduce physical inactivity and SB in Australia, particularly among the subgroups at the highest risk of these unhealthy behaviours.

Associations of physical activity and sedentary behavior with academic skills--a follow-up study among primary school children.

PubMed

Haapala, Eero A; Poikkeus, Anna-Maija; Kukkonen-Harjula, Katriina; Tompuri, Tuomo; Lintu, Niina; Väistö, Juuso; Leppänen, Paavo H T; Laaksonen, David E; Lindi, Virpi; Lakka, Timo A

2014-01-01

There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children. The participants were 186 children (107 boys, 79 girls, 6-8 yr) who were followed-up in Grades 1-3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1-3. Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1-3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1-3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1-3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1-3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents. Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls. ClinicalTrials.gov: NCT01803776.

Brush head composition, wear profile, and cleaning efficacy: an assessment of three electric brush heads using in vitro methods.

PubMed

Kaiser, Eva; Meyners, Michael; Markgraf, Dirk; Stoerkel, Ulrich; von Koppenfels, Roxana; Adam, Ralf; Soukup, Martin; Wehrbein, Heinrich; Erbe, Christina

2014-01-01

The objective of this research was to evaluate a current store brand (SB) brush head for composition/physical characteristics, Wear Index (WI), and cleaning efficacy versus the previous SB brush head refill design (SB control) and the Oral-B Precision Clean brush head (positive control, PC). This research consisted of three parts: 1) Analytical analysis using Fourier Transform Infrared (FT-IR) spectrometry to evaluate the chemical composition of the current SB brush head bristles relative to the SB control. In addition, physical parameters such as bristle count and diameter were determined. 2) Wear Index (WI) investigation to determine the Wear Index scores of in vitro-aged brush heads at four weeks (one month) and 13 weeks (three months) by a trained investigator. To "age" the brush heads, a robot system was used as a new alternative in vitro method to simulate aging by consumer use. 3) Robot testing to determine the cleaning performance of in vitro-aged brush heads, comparing one month-aged current SB brush heads with the SB control (one and three months-aged) and the PC brush heads (three months-aged) in a standardized fashion. 1) FT-IR analysis revealed that the chemical composition of the current and control SB refill brush heads is identical. In terms of physical parameters, the current SB brush head has 12% more bristles and a slightly oval brush head compared to the round brush head of the SB control. 2) Wear Index analysis showed there was no difference in the one month-aged current SB brush head versus the one month-aged SB control (1.67 vs. 1.50, p = 0.65) or versus the three months-aged PC brush head (1.67 vs. 1.50, p = 0.65). The one month-aged current SB brush head demonstrated statistically significantly less wear than the three months-aged SB control (1.67 vs. 2.67, p = 0.01). 3) Analysis of cleaning efficacy shows that the one month-aged current SB brush head had improved cleaning performance over the one month-aged SB control brush head (p < 0.05), despite no statistically significant difference in wear. Both the one month-aged current and control SB brush heads showed statistically significantly lower cleaning performance compared to the three months-aged PC brush heads (p < 0.01). While the current SB brush head showed improved cleaning over the SB control, it demonstrated significantly lower durability and cleaning in comparison to the PC brush head. Dental professionals should be aware of these differences, both in durability and in cleaning performance, when recommending brush heads to their patients.

Correlating microbial community profiles with geochemical conditions in a watershed heavily contaminated by an antimony tailing pond.

PubMed

Xiao, Enzong; Krumins, Valdis; Tang, Song; Xiao, Tangfu; Ning, Zengping; Lan, Xiaolong; Sun, Weimin

2016-08-01

Mining activities have introduced various pollutants to surrounding aquatic and terrestrial environments, causing adverse impacts to the environment. Indigenous microbial communities are responsible for the biogeochemical cycling of pollutants in diverse environments, indicating the potential for bioremediation of such pollutants. Antimony (Sb) has been extensively mined in China and Sb contamination in mining areas has been frequently encountered. To date, however, the microbial composition and structure in response to Sb contamination has remained overlooked. Sb and As frequently co-occur in sulfide-rich ores, and co-contamination of Sb and As is observed in some mining areas. We characterized, for the first time, the microbial community profiles and their responses to Sb and As pollution from a watershed heavily contaminated by Sb tailing pond in Southwest China. The indigenous microbial communities were profiled by high-throughput sequencing from 16 sediment samples (535,390 valid reads). The comprehensive geochemical data (specifically, physical-chemical properties and different Sb and As extraction fractions) were obtained from river water and sediments at different depths as well. Canonical correspondence analysis (CCA) demonstrated that a suite of in situ geochemical and physical factors significantly structured the overall microbial community compositions. Further, we found significant correlations between individual phylotypes (bacterial genera) and the geochemical fractions of Sb and As by Spearman rank correlation. A number of taxonomic groups were positively correlated with the Sb and As extractable fractions and various Sb and As species in sediment, suggesting potential roles of these phylotypes in Sb biogeochemical cycling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical activity and sedentary behavior in metabolically healthy obese young women

USDA-ARS?s Scientific Manuscript database

Studies of physical activity (PA) and sedentary behavior (SB) in metabolically healthy obese (MHO) have been limited to postmenopausal white women. We sought to determine whether PA and SB differ between MHO and metabolically abnormal obese (MAO), in young black and white women....

Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension

PubMed Central

Littlejohn, Nicole K.

2015-01-01

Metabolic disease, specifically obesity, has now become the greatest challenge to improving cardiovascular health. The renin-angiotensin system (RAS) exists as both a circulating hormone system and as a local paracrine signaling mechanism within various tissues including the brain, kidney, and adipose, and this system is strongly implicated in cardiovascular health and disease. Growing evidence also implicates the RAS in the control of energy balance, supporting the concept that the RAS may be mechanistically involved in the pathogenesis of obesity and obesity hypertension. Here, we review the involvement of the RAS in the entire spectrum of whole organism energy balance mechanisms, including behaviors (food ingestion and spontaneous physical activity) and biological processes (digestive efficiency and both aerobic and nonaerobic resting metabolic rates). We hypothesize that opposing, tissue-specific effects of the RAS to modulate these various components of energy balance can explain the apparently paradoxical results reported by energy-balance studies that involve stimulating, versus disrupting, the RAS. We propose a model in which such opposing and tissue-specific effects of the RAS can explain the failure of simple, global RAS blockade to result in weight loss in humans, and hypothesize that obesity-mediated uncoupling of endogenous metabolic rate control mechanisms can explain the phenomenon of obesity-related hypertension. PMID:26491099

Processing of the signals from the Liquid Xenon Calorimeter for timing measurements

NASA Astrophysics Data System (ADS)

Epshteyn, L. B.; Grebenuyk, A. A.; Kozyrev, A. N.; Logashenko, I. B.; Mikhaylov, K. Yu.; Ruban, A. A.; Yudin, Yu. V.

2017-02-01

One of the goals of the Cryogenic Magnetic Detector at Budker Institute of Nuclear Physics SB RAS (Novosibirsk, Russia) is a study of hadron production in electron-positron collisions near threshold. The neutron-antineutron pair production events can be detected only by the calorimeters. In the barrel calorimeter the antineutron annihilation typically occurs about 5 ns or later after the beams crossing. For identification of such events it is necessary to measure the time of flight of particles to the LXe-calorimeter with an accuracy of about a few nanoseconds. The LXe-calorimeter consists of 14 layers of ionization chambers with two readout: anode and cathode. The duration of charge collection to the anodes is about 4.5 μs, while the required accuracy of measuring of the signal arrival time is less than 1/1000 of that (i.e. 4.5 ns). Besides, the signals' shapes differ substantially from event to event, so the signal arrival time is measured in two stages. In the paper we describ the development of the special electronics which performs waveform digitization and the on-line measurement of signals' arrival times and amplitudes.

Associations of Physical Activity and Sedentary Behavior with Academic Skills – A Follow-Up Study among Primary School Children

PubMed Central

Haapala, Eero A.; Poikkeus, Anna-Maija; Kukkonen-Harjula, Katriina; Tompuri, Tuomo; Lintu, Niina; Väistö, Juuso; Leppänen, Paavo H. T.; Laaksonen, David E.; Lindi, Virpi; Lakka, Timo A.

2014-01-01

Background There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children. Methods The participants were 186 children (107 boys, 79 girls, 6–8 yr) who were followed-up in Grades 1–3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1–3. Results Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1–3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1–3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1–3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1–3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents. Conclusions Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls. Trial Registration ClinicalTrials.gov: NCT01803776 PMID:25207813

Characterizing the context of sedentary lifestyles in a representative sample of adults: a cross-sectional study from the physical activity measurement study project.

PubMed

Kim, Youngwon; Welk, Gregory J

2015-12-09

Research has clearly demonstrated that excess time spent on sedentary behavior (SB) increases health risks in the population. However, the lack of information on the context of SB in the population prevents a detailed understanding of sedentary lifestyles. The purpose of this study was to characterize the context of SB in a representative sample of adults and to examine differences across various socio-demographic indicators. A diverse sample of 1442 adults (ages 20-71 year) completed an interviewer-administered 24-h activity recall to provide detailed information about the time, type and location of the previous day's activities. All reported activities were matched with MET scores from the Compendium of Physical Activity but only SB (i.e., METS < 1.5) were extracted for the present analyses. The reported SB were broadly distributed across 5 primary location categories (Work: 27.5%, Community: 24.8%, Home/Indoor: 20.5%, Home/Outdoor: 15.8%, and Transportation: 11.3%). Patterns of SB allocations varied considerably across different socio-demographic indicators indicating the extreme variability in SB in the population. The findings provide unique insights about the context of SB at the population level, and can serve as a guide for developing intervention/policy studies to reduce sedentary time and minimize disparities in SB.

Electrical and optical characterization of n-InAsSb/n-GaSb heterojunctions

NASA Astrophysics Data System (ADS)

Lackner, D.; Martine, M.; Cherng, Y. T.; Steger, M.; Walukiewicz, W.; Thewalt, M. L. W.; Mooney, P. M.; Watkins, S. P.

2010-01-01

We report the electrical properties of n-InAsSb/n-GaSb heterojunctions as a function of the GaSb doping concentration. Because of the staggered type II band alignment, strong electron accumulation occurs on the InAsSb side. For low GaSb doping, depletion occurs on the GaSb side resulting in a Schottky-like junction as previously reported. As the GaSb doping increases, the built-in voltage as well as depletion width decreases as shown using self-consistent simulations. For GaSb doping levels above 5×1017 cm-3, the junction loses its rectifying properties due to tunneling. Under zero and reverse bias voltage, the photoresponse of these diodes is solely due to the photovoltaic effect in the GaSb depletion region. For forward bias voltages >400 mV, we also observed a photoconductive response from the InAsSb layer. The proposed physical mechanism is quite different from the one suggested in a recent paper.

Preparation and Thermoelectric Properties of Semiconcucting Zn(sub 4) Sb(sub 3)

NASA Technical Reports Server (NTRS)

Caillat, T.; Fleurial, J. P.; Barshchevsky, A.

1996-01-01

Hot-pressed samples fothe semiconducting compound Beta - Zn(sub 4) Sb(sub 3) were prepared and characterized by x-ray and microprobe analysis. Some physical properties of Beta - Zn(sub 4) Sb(sub 3) were determined and its thermoelectric properties measured between room temperature and 650K.

Motivators and Barriers to Reducing Sedentary Behavior Among Overweight and Obese Older Adults.

PubMed

Greenwood-Hickman, Mikael Anne; Renz, Anne; Rosenberg, Dori E

2016-08-01

To explore individual, social, environmental, and program-related motivators, barriers, and impacts of sedentary behavior (SB) reduction among a group of overweight and obese older adults aged 60 and older. Semistructured interviews were conducted with 24 participants following a SB reduction intervention. Transcripts from these interviews were iteratively coded by a team, and key themes were defined and refined guided by the social-ecological framework. Motivators included the desire to improve health, newly acquired awareness of SB, the ease of incorporating SB reduction into current lifestyle, an adaptable environment, and the use of reminders. Barriers included existing health conditions, enjoyment of sedentary activities, unadaptable environments, fatigue, and difficulty understanding SB reduction as distinct from physical activity (PA). Participants reported impacts on physical and mental health and changes in awareness, exercise, and daily activity. Although in many ways motivators and barriers to reducing SB are similar to those of PA, SB interventions have special considerations and may ultimately be easier for some individuals to incorporate into their lifestyle. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Cross-Disciplinary and Cross-Cultural Study of Directives in Discussions and Conclusions of Research Articles

ERIC Educational Resources Information Center

Jalilifar, Alireza; Mehrabi, Khodayar

2014-01-01

The current study provided cross-cultural and cross-disciplinary analyses of the distribution of directives in discussion and conclusion sections of English and Persian research articles (RAs) in disciplines of physics, chemistry, counseling, and sociology, representing hard and soft sciences, respectively. To that aim, 80 RAs from both English…

Astrophysics and astronomy (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 26 January 2011)

NASA Astrophysics Data System (ADS)

2011-10-01

An Astrophysics and Astronomy scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) was held in the Conference Hall of the P N Lebedev Physical Institute, RAS, on 26 January 2011. The following reports were put on the session's agenda posted on the web site www.gpad.ac.ru of the Physical Sciences Division, RAS: (1) Cherepashchuk A M (Sternberg Astronomical Institute, Moscow State University, Moscow) "Investigation of X-ray sources"; (2) Shustov B M (Institute of Astronomy, Russian Academy of Sciences, Moscow) "Asteroid and comet hazards: physical and other aspects"; (3) Sazhin M V (Sternberg Astronomical Institute, Moscow State University, Moscow) "Search for cosmic strings"; (4) Zakharov A F (Russian Federation State Scientific Center 'A I Alikhanov Institute for Theoretical and Experimental Physics', Moscow) "Exoplanet search using gravitational microlensing". Papers written on the basis of the reports are published below. • Optical investigations of X-ray binary systems, A M Cherepashchuk Physics-Uspekhi, 2011, Volume 54, Number 10, Pages 1061-1067 • Asteroid and comet hazards: the role of physical sciences in solving the problem, B M Shustov Physics-Uspekhi, 2011, Volume 54, Number 10, Pages 1068-1071 • Search for cosmic strings using optical and radio astronomy methods, O S Sazhina, M V Sazhin, M Capaccioli, G Longo Physics-Uspekhi, 2011, Volume 54, Number 10, Pages 1072-1077 • Search for exoplanets using gravitational microlensing, A F Zakharov Physics-Uspekhi, 2011, Volume 54, Number 10, Pages 1077-1084

Quantum oscillations and coherent interlayer transport in a new topological Dirac semimetal candidate YbMnSb2

NASA Astrophysics Data System (ADS)

Wang, Yi-Yan; Xu, Sheng; Sun, Lin-Lin; Xia, Tian-Long

2018-02-01

Dirac semimetals, which host Dirac fermions and represent a new state of quantum matter, have been studied intensively in condensed-matter physics. The exploration of new materials with topological states is important in both physics and materials science. We report the synthesis and the transport properties of high-quality single crystals of YbMnSb2. YbMnSb2 is a new compound with metallic behavior. Quantum oscillations, including Shubnikov-de Haas (SdH) oscillation and de Haas-van Alphen-type oscillation, have been observed at low temperature and high magnetic field. Small effective masses and nontrivial Berry phase are extracted from the analyses of quantum oscillations, which provide the transport evidence for the possible existence of Dirac fermions in YbMnSb2. The measurements of angular-dependent interlayer magnetoresistance indicate that the interlayer transport is coherent. The Fermi surface of YbMnSb2 possesses a quasi-two-dimensional characteristic as determined by the angular dependence of SdH oscillation frequency. These findings suggest that YbMnSb2 is a new candidate of topological Dirac semimetals.

CONFERENCES AND SYMPOSIA: Seventy years of the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Waves Propagation (IZMIRAN) (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 25 November 2009)

NASA Astrophysics Data System (ADS)

2010-08-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences dedicated to the 70th anniversary of the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation of the Russian Academy of Sciences (IZMIRAN) (Troitsk, Moscow region) was held in the conference hall of IZMIRAN on 25 November 2009. The following reports were put on the session agenda posted on the web site www.gpad.ac.ru of the Physical Sciences Division, RAS: (1) Gurevich A V (Lebedev Physical Institute RAS, Moscow) "The role of cosmic rays and runaway electron breakdown in atmospheric lightning discharges"; (2) Aleksandrov E B (Ioffe Physical Technical Institute, RAS, St. Petersburg) "Advances in quantum magnetometry for geomagnetic research"; (3) Dorman L I (IZMIRAN, Troitsk, Moscow region, CR & SWC, Israel) "Cosmic ray variations and space weather"; (4) Mareev E A (Institute of Applied Physics, RAS, Nizhnii Novgorod) "Global electric circuit research: achievements and prospects"; (5) Tereshchenko E D, Safargaleev V V (Polar Geophysical Institute, Kola Research Center, RAS, Murmansk) "Geophysical research in Spitsbergen Archipelago: status and prospects"; (6) Gulyaev Yu V, Armand N A, Efimov A I, Matyugov S S, Pavelyev A G, Savich N A, Samoznaev L N, Smirnov V V, Yakovlev O I (Kotel'nikov Institute of Radio Engineering and Electronics RAS, Fryazino Branch, Fryazino, Moscow region) "Results of solar wind and planetary ionosphere research using radiophysical methods"; (7) Kunitsyn V E (Lomonosov Moscow State University, Moscow) "Satellite radio probing and the radio tomography of the ionosphere"; (8) Kuznetsov V D (IZMIRAN, Troitsk, Moscow region) "Space Research at the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation, Russian Academy of Sciences." Papers based on reports 2-8 are published below. The main contents of report 1 are reproduced in A V Gurevich's review, "Nonlinear effects in the ionosphere" [Phys. Usp. 50 1091 (2007)] and in the paper by A V Gurevich et al., "Nonlinear phenomena in the ionospheric plasma. Effects of cosmic rays and runaway breakdown on thunderstorm discharges" [Phys. Usp. 52 735 (2009)]. • Advances in quantum magnetometry for geomagnetic research , E B Aleksandrov Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 487-496 • Cosmic ray variations and space weather, L I Dorman Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 496-503 • Global electric circuit research: achievements and prospects, E A Mareev Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 504-511 • Geophysical research in Spitsbergen Archipelago: status and prospects, V V Safargaleev, E D Tereshchenko Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 511-517 • Results of solar wind and planetary ionosphere research using radiophysical methods, N A Armand, Yu V Gulyaev, A L Gavrik, A I Efimov, S S Matyugov, A G Pavelyev, N A Savich, L N Samoznaev, V M Smirnov, O I Yakovlev Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 517-523 • Satellite radio probing and radio tomography of the ionosphere, V E Kunitsyn, E D Tereshchenko, E S Andreeva, I A Nesterov Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 523-528 • Space research at the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation, Russian Academy of Sciences , V D Kuznetsov Physics-Uspekhi, 2010, Volume 53, Number 5, Pages 528-534

Classes of Physical Activity and Sedentary Behavior in 5th Grade Children

PubMed Central

Dowda, Marsha; Dishman, Rod K; Pate, Russell R.

2016-01-01

Objectives To identify classes of physical activity (PA) and sedentary behaviors (SB) in 5th grade children, associated factors, and trajectories of change into 7th grade. Methods This study included n=495 children (221 boys, 274 girls) who participated in the Transitions and Activity Changes in Kids (TRACK) Study. PA was assessed objectively and via self-report. Children, parents, and school administrators completed surveys to assess related factors. Latent class analysis, growth modeling, and adjusted multinomial logistic regression procedures were used to classify children based on self-reported PA and SB and examine associated factors. Results Three classes of behavior were identified: Class 1: Low PA/Low SB, Class 2: Moderate PA/High SB, and Class 3: High PA/High SB (boys) or Class 3: High PA (girls). Class 3 children had higher levels of self-efficacy (boys), and enjoyment, parental support, and physical activity equipment at home (girls). Class 2 boys and Class 3 girls did not experience decline in PA (accelerometer) over time. Conclusions Self-efficacy (boys) and home environment (girls) may play a role in shaping patterns of PA in children. Findings may help to inform future interventions to encourage children to meet national PA guidelines. PMID:27103414

Level and potential social-ecological factors associated with physical inactivity and sedentary behavior among Moroccan school-age adolescents: a cross-sectional study.

PubMed

El-Ammari, Abdelghaffar; El Kazdouh, Hicham; Bouftini, Siham; El Fakir, Samira; El Achhab, Youness

2017-05-18

Creating a successful intervention that supports an active lifestyle and prevents sedentary one requires a better understanding of the factors associated with physical inactivity (PI) and sedentary behavior (SB). However, these factors have not been assessed among Moroccan adolescents. This study aimed to determine prevalence of PI and SB and to explore their potential social-ecological associated factors in school-age adolescents. In this cross-sectional study, 764 students (age range, 14-19 years) were enrolled from six schools in Taza city, Morocco. The Global School-based Student Health Survey was used to collect data about variables. We used bivariate and multivariate analyses to assess relations between dependent and independent variables. Overall, the prevalence of PI was 79.5% and SB was 36.5%. Among girls, these rates were higher (87.0 and 39.1%, respectively) than rates shown in boys (70.9 and 33.6%, respectively). In the multivariate logistic regression analysis, PI was associated with the following variables: illiterate father, hunger, suicidal ideation, inadequate vegetable consumption, and absence from physical education classes. Age, inadequate vegetable consumption, and absenteeism were associated with SB. The prevalence of PI and SB is high, especially among girls. Thus, there is an urgent need to implement appropriate interventions to reduce PI and SB levels in secondary school-age adolescents and the associated factors identified can be useful.

Fine genetic mapping of spot blotch resistance gene Sb3 in wheat (Triticum aestivum).

PubMed

Lu, Ping; Liang, Yong; Li, Delin; Wang, Zhengzhong; Li, Wenbin; Wang, Guoxin; Wang, Yong; Zhou, Shenghui; Wu, Qiuhong; Xie, Jingzhong; Zhang, Deyun; Chen, Yongxing; Li, Miaomiao; Zhang, Yan; Sun, Qixin; Han, Chenggui; Liu, Zhiyong

2016-03-01

Spot blotch disease resistance gene Sb3 was mapped to a 0.15 centimorgan (cM) genetic interval spanning a 602 kb physical genomic region on chromosome 3BS. Wheat spot blotch disease, caused by B. sorokiniana, is a devastating disease that can cause severe yield losses. Although inoculum levels can be reduced by planting disease-free seed, treatment of plants with fungicides and crop rotation, genetic resistance is likely to be a robust, economical and environmentally friendly tool in the control of spot blotch. The winter wheat line 621-7-1 confers immune resistance against B. sorokiniana. Genetic analysis indicates that the spot blotch resistance of 621-7-1 is controlled by a single dominant gene, provisionally designated Sb3. Bulked segregant analysis (BSA) and simple sequence repeat (SSR) mapping showed that Sb3 is located on chromosome arm 3BS linked with markers Xbarc133 and Xbarc147. Seven and twelve new polymorphic markers were developed from the Chinese Spring 3BS shotgun survey sequence contigs and 3BS reference sequences, respectively. Finally, Sb3 was mapped in a 0.15 cM genetic interval spanning a 602 kb physical genomic region of Chinese Spring chromosome 3BS. The genetic and physical maps of Sb3 provide a framework for map-based cloning and marker-assisted selection (MAS) of the spot blotch resistance.

Intrinsic Topological Insulator Bi1.5Sb0.5Te3-xSex Thin Crystals

NASA Astrophysics Data System (ADS)

Wang, Wei; Li, Li; Zou, Wenqin; He, Liang; Song, Fengqi; Zhang, Rong; Wu, Xiaoshan; Zhang, Fengming

2015-01-01

The quaternary topological insulator (Bi,Sb)2(Te,Se)3 has demonstrated topological surface states with an insulating bulk. Scientists have identified an optimized composition of Bi1.5Sb0.5Te1.7Se1.3 with the highest resistivity reported. But the physics that drive to this composition remains unclear. Here we report the crystal structure and the magneto-transport properties of Bi1.5Sb0.5Te3-xSex (BSTS) series. A correlation between the structure and the physical properties has been revealed. We found out that within the rhombohedral structure, the composition with most Te substituting Se has the highest resistivity. On the other hand, segregation of other composition phases will introduce much higher bulk concentration.

Effects of Cu and Ag as ternary and quaternary additions on some physical properties of SnSb7 bearing alloy

NASA Astrophysics Data System (ADS)

El-Bediwi, A. B.

2004-02-01

The structure, electrical resistivity, and elastic modulus of SnSb7 and SnSb7X (X = Cu , Ag, or Cu and Ag) rapidly solidified alloys have been investigated using X-ray diffractometer, double bridge, and dynamic resonance techniques. Copper and silver additions to SnSb result in the formation of a eutectic matrix containing embedded crystals (intermetallic phases) of SnCu, SnAg, and SnSb. The hard crystals SnCu, SnAg, and SnSb increase the overall hardness and wear resistance of SnSb bearing alloys. Addition of copper and silver improves internal friction, electrical conductivity, and elastic modulus values of SnSb rapidly solidified bearing alloys. The internal friction, elastic modulus, and electrical resistivity values are relatively sensitive to the composition of the intermediate phases in the matrix. The SbSb(7)Cu(2)g(2) has better properties (lowest internal friction, cost, adequate elastic modulus, and electrical resistivity) for bearing alloys as compared to cast iron and bronzes.

Design and Performance of McRas in SCMs and GEOS I/II GCMs

NASA Technical Reports Server (NTRS)

Sud, Yogesh C.; Einaudi, Franco (Technical Monitor)

2000-01-01

The design of a prognostic cloud scheme named McRAS (Microphysics of clouds with Relaxed Arakawa-Schubert Scheme) for general circulation models (GCMs) will be discussed. McRAS distinguishes three types of clouds: (1) convective, (2) stratiform, and (3) boundary-layer types. The convective clouds transform and merge into stratiform clouds on an hourly time-scale, while the boundary-layer clouds merge into the stratiform clouds instantly. The cloud condensate converts into precipitation following the auto-conversion equations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, as well as diffuse both horizontally and vertically with a fully interactive cloud-microphysics throughout the life-cycle of the cloud, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry. An evaluation of McRAS in a single column model (SCM) with the GATE Phase III and 5-ARN CART datasets has shown that together with the rest of the model physics, McRAS can simulate the observed temperature, humidity, and precipitation without many systematic errors. The time history and time mean incloud water and ice distribution, fractional cloudiness, cloud optical thickness, origin of precipitation in the convective anvil and towers, and the convective updraft and downdraft velocities and mass fluxes all show a realistic behavior. Performance of McRAS in GEOS 11 GCM shows several satisfactory features but some of the remaining deficiencies suggest need for additional research involving convective triggers and inhibitors, provision for continuously detraining updraft, a realistic scheme for cumulus gravity wave drag, and refinements to physical conditions for ascertaining cloud detrainment level.

No Evidence of Reciprocal Associations between Daily Sleep and Physical Activity.

PubMed

Mitchell, Jonathan A; Godbole, Suneeta; Moran, Kevin; Murray, Kate; James, Peter; Laden, Francine; Hipp, J Aaron; Kerr, Jacqueline; Glanz, Karen

2016-10-01

This study aimed to determine whether physical activity patterns are associated with sleep later at night and if nighttime sleep is associated with physical activity patterns the next day among adult women. Women (N = 353) living throughout the United States wore a wrist and a hip accelerometer for 7 d. Total sleep time (TST, hours per night) and sleep efficiency (SE, %) were estimated from the wrist accelerometer, and moderate to vigorous physical activity (MVPA, >1040 counts per minute, h·d) and sedentary behavior (SB, <100 counts per minute, h·d) were estimated from the hip accelerometer. Mixed-effects models adjusted for age, race, body mass index, education, employment, marital status, health status, and hip accelerometer wear time were used to analyze the data. Follow-up analyses using quantile regression were used to investigate associations among women with below average TST and MVPA and above average SB. The average age of our sample was 55.5 yr (SD = 10.2 yr). The majority of participants were White (79%) and married (72%), and half were employed full time (49%). The participants spent on average 8.9 and 1.1 h·d in SB and MVPA, respectively, and 6.8 h per night asleep. No associations were observed between MVPA and SB with nighttime TST or SE. There were no associations between nighttime TST and SE with MVPA or SB the next day. The findings were the same in the quantile regression analyses. In free-living adult women, accelerometry-estimated nighttime sleep and physical activity patterns were not associated with one another. On the basis of our observational study involving a sample of adult women, higher physical activity will not necessarily improve sleep at night on a day-to-day basis (and vice versa).

The Influence of Growth Temperature on Sb Incorporation in InAsSb, and the Temperature-dependent Impact of Bi Surfactants

DTIC Science & Technology

2014-01-01

resolution X - ray diffraction (XRD) were collected for all samples, and reciprocal space maps (RSMs) were collected from selected samples. The complete data...exposure. The lines represent the model fit. 19 13 Figure 1. Triple axis x - ray diffraction from the bi-layered InAsSb structures grown on GaSb at...Applied Physics, Structural properties of bismuth‐bearing semiconductor alloys, 63 (1988) 107. 18 12 Figure Captions Figure 1. Triple axis x - ray

Physical Education Classes, Physical Activity, and Sedentary Behavior in Children.

PubMed

Silva, Diego Augusto Santos; Chaput, Jean-Philippe; Katzmarzyk, Peter T; Fogelholm, Mikael; Hu, Gang; Maher, Carol; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L; Standage, Martyn; Tudor-Locke, Catrine; Tremblay, Mark S

2018-05-01

This study aimed to examine the associations between participation frequency in physical education (PE) classes and objective measures of physical activity (PA) and sedentary behavior (SB) in children from 12 countries at different levels of development. This multinational, cross-sectional study included 5874 children 9-11 yr old from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. PA and SB were monitored for seven consecutive days using a waist-worn accelerometer. PA and SB data were presented for weekdays (times in and out of school) and weekend days. Participation frequency in PE classes was determined by questionnaire. Multilevel modeling analyses stratified by sex were used. Overall, 24.8% of children self-reported participation in PE classes ≥3 times per week (25.3% in high-income countries [HIC] and 24.3% in low- and middle-income countries [LMIC]). After adjusting for age, sex, parental education, and body mass index z-score, results showed that children from low- and middle-income countries who took PE classes one to two times per week were more likely to present better indicators of PA and shorter time in SB in and out of school. In HIC, boys that participated in PE classes were more likely to meet the moderate-to-vigorous PA recommendations and to present better indicators of PA (in school) and shorter time in SB in and out of school. For girls in HIC, attending PE classes increased the likelihood of spending more time in moderate-to-vigorous PA, especially if they attended ≥3 times per week. Attending PE classes is associated with a higher level of PA and a lower level of SB in and out of school during weekdays in children from countries at various levels of development.

Objectively Measured Patterns of Activities of Different Intensity Categories and Steps Taken Among Working Adults in a Multi-ethnic Asian Population.

PubMed

Müller-Riemenschneider, Falk; Ng, Sheryl Hui Xian; Koh, David; Chu, Anne Hin Yee

2016-06-01

To objectively assess sedentary behavior (SB), light- and moderate-to-vigorous intensity physical activity (MVPA), and steps among Singaporean office-based workers across days of the week. A convenience sample of office-based employees of a public University was recruited. Time spent for SB, light-, and MVPA using different validated accelerometry counts per minute (CPM), and step count were determined. Depending on applied CPM for SB (less than 100, less than 150 and less than 200 CPM), 107 working adults spent between 69.2% and 76.4% of their daily wakeful time in SB. Time spent in SB and MVPA were higher on weekdays than weekends. The hourly analysis highlights patterns of greater SB during usual working hours on weekdays but not on weekends. SB at work contributes greatly toward total daily sitting time. Low PA levels and high SB levels were found on weekends.

Mediated Effects of Perceived Competence on Youth Physical Activity and Sedentary Behavior

ERIC Educational Resources Information Center

Bai, Yang; Chen, Senlin; Vazou, Spyridoula; Welk, Gregory J.; Schaben, Jodee

2015-01-01

Purpose: This study evaluates whether physical activity (PA) and sedentary behavior (SB) are influenced by a common mediating relationship. Method: A total of 1,552 participants in 3rd to 12th grade completed an online survey that included assessments of PA at school (PAS), PA at home (PAH), and SB as well as a battery of psychosocial variables…

Concurrent Associations of Physical Activity and Screen-Based Sedentary Behavior on Obesity Among US Adolescents: A Latent Class Analysis.

PubMed

Kim, Youngdeok; Barreira, Tiago V; Kang, Minsoo

2016-01-01

Independent associations of physical activity (PA) and sedentary behavior (SB) with obesity are well documented. However, little is known about the combined associations of these behaviors with obesity in adolescents. The present study examines the prevalence of concurrent levels of PA and SB, and their associations with obesity among US adolescents. Data from a total of 12 081 adolescents who participated in the Youth Risk Behaviors Survey during 2012-2013 were analyzed. A latent class analysis was performed to identify latent subgroups with varying combined levels of subjectively measured PA and screen-based SB. Follow-up analysis examined the changes in the likelihood of being obese as determined by the Center for Disease Control and Prevention Growth Chart between latent subgroups. Four latent subgroups with varying combined levels of PA and SB were identified across gender. The likelihood of being obese was significantly greater for the subgroups featuring either or both Low PA or High SB when compared with High PA/Low SB across genders (odds ratio [OR] ranges, 2.1-2.7 for males and 9.6-23.5 for females). Low PA/High SB showed the greater likelihood of being obese compared to subgroups featuring either or both High PA and Low SB (OR ranges, 2.2-23.5) for female adolescents only. The findings imply that promoting sufficient levels of PA while reducing SB should be encouraged in order to reduce obesity risk among adolescents, particularly for males. The risk of obesity for female adolescents can be reduced by engaging in either high levels of PA or low levels of SB.

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation.

PubMed

Chen, Wenjin; Guo, Shengdong; Wang, Shenggang

2016-10-22

BACKGROUND The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. MATERIAL AND METHODS Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4-L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR). In addition, luciferase reporter assay was performed to explore whether RAB23 was a target of miR-16, and qRT-PCR and Western blotting were used to confirm the regulation between RAB23 and miR-16. RESULTS The level of miR-16 was significantly decreased in the CFA-induced inflammatory pain. Intrathecal injection of miR-16 alleviates pain response and raised pain threshold. The level of RAB23 was significantly increased in the pain model, and intrathecal injection of RAB23 aggravated pain response. Luciferase reporter assay confirmed that RAB23 was a direct target of miR-16, and RAB23 was negatively regulated by miR-16. In addition, we found that simultaneous administration of SB203580 and miR-16 further alleviates pain response compared to only administration of miR-16. CONCLUSIONS Our findings suggest that miR-16 relieves chronic inflammatory pain by targeting RAB23 and inhibiting p38 MAPK activation.

Principles of establishing material cycling with a high degree of closure in the experimental model of a BTLSS intended for a rated "fraction of a human"

NASA Astrophysics Data System (ADS)

Tikhomirov, Alexander A.; Ushakova, Sofya; Velichko, Vladimir; Tikhomirova, Natalia; Shikhov, Valentin; Trifonov, Sergey V.

2016-07-01

A promising way to develop future biotechnical life support systems (BTLSS) is to construct experimental models and establish the cycling intended for a fraction of a human. Being of relatively low cost, such models provide an opportunity to test effectively closed process that could be further transferred to the real BTLSS with humans. Researchers of the IBP SB RAS are developing an adequate BTLSS model with the loops closed to a high degree. To attain high closure of mass exchange processes, plants in the phototrophic compartment are cultivated under intensive lighting conditions, created by using modern LED irradiators of enhanced power, equipped with lens optics. The higher plant compartment has been renewed and broadened by including soybean plants, which improve the vegetable part of the human diet and make it more diverse. It is very important that the operation of the physicochemical installation for waste mineralization fully matches the composition of the atmosphere of plant growth chambers: the purified gaseous components of this installation enter the common atmosphere of the system, without causing any deviations from the norm in the gaseous composition. This proves the eco-friendliness of the developed physicochemical method of waste mineralization and shows that the gaseous components resulting from waste mineralization can be included in the system mass exchange. A system for including human respiration into the gas exchange of the BTLSS has been developed and tested; the associated gas exchange and water exchange dynamics have been analyzed. Results of the functioning of the experimental model of the BTLSS for several months are proposed for discussion in order to get insight into the formation of dynamic characteristics of cycling processes and factors determining them. The study was supported by the grant of the Russian Science Foundation (Project 14-14-00599) and carried out at the IBP SB RAS.

Dog ownership and health-related physical activity among Japanese adults.

PubMed

Oka, Koichiro; Shibata, Ai

2009-07-01

Dog ownership appears to have associated health benefits as a result of increased physical activity through dog walking. This study examined the association between dog ownership and health-related physical activity among Japanese adults. Male and female respondents to an Internet-based cross-sectional survey were divided into the following groups: dog owner (DOG), nondog pet owner (NDOG), and nonpet owner (NPOG). Moderate and vigorous physical activity amount (MVPA), walking amount (Walking), and sedentary behavior time (SB) were estimated from the International Physical Activity Questionnaire. Analyses of covariance and logistic regression analysis were used. The differences in MVPA, Walking, and SB were statistically significant among the three groups. DOG had a significantly greater amount of MVPA than NDOG and NPOG. DOG also had a significantly greater amount of Walking and less SB time than NPOG, and DOG was 1.5 times more likely to meet the physical activity recommendation than NDOG and NPOG. The dog owners had higher physical activity levels than owners of other kinds of pets and those without any pets, suggesting that dogs may play a major role in promoting physical activity. However, only 30% of the dog owners met the recommended criteria for physical activity.

Combinations of physical activity, sedentary behaviour and sleep: relationships with health indicators in school-aged children and youth.

PubMed

Saunders, Travis John; Gray, Casey Ellen; Poitras, Veronica Joan; Chaput, Jean-Philippe; Janssen, Ian; Katzmarzyk, Peter T; Olds, Timothy; Connor Gorber, Sarah; Kho, Michelle E; Sampson, Margaret; Tremblay, Mark S; Carson, Valerie

2016-06-01

The purpose of this systematic review was to determine how combinations of physical activity (PA), sedentary behaviour (SB), and sleep were associated with important health indicators in children and youth aged 5-17 years. Online databases (MEDLINE, EMBASE, SPORTdiscus, CINAHL, and PsycINFO) were searched for relevant studies examining the relationship between time spent engaging in different combinations of PA, SB, and sleep with the following health indicators: adiposity, cardiometabolic biomarkers, physical fitness, emotional regulation/psychological distress, behavioural conduct/pro-social behaviour, cognition, quality of life/well-being, injuries, bone density, motor skill development, and self-esteem. PA had to be objectively measured, while sleep and SB could be objectively or subjectively measured. The quality of research evidence and risk of bias for each health indicator and for each individual study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. A total of 13 cross-sectional studies and a single prospective cohort study reporting data from 36 560 individual participants met the inclusion criteria. Children and youth with a combination of high PA/high sleep/low SB had more desirable measures of adiposity and cardiometabolic health compared with those with a combination of low PA/low sleep/high SB. Health benefits were also observed for those with a combination of high PA/high sleep (cardiometabolic health and adiposity) or high PA/low SB (cardiometabolic health, adiposity and fitness), compared with low PA/low sleep or low PA/high SB. Of the 3 movement behaviours, PA (especially moderate- to vigorous-intensity PA) was most consistently associated with desirable health indicators. Given the lack of randomized trials, the overall quality of the available evidence was low.

Association of physiological and psychological health outcomes with physical activity and sedentary behavior in adults with type 2 diabetes

PubMed Central

Garcia, Jeanette M; Cox, Daniel; Rice, David J

2017-01-01

Purpose To examine the association between change in moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) over a 6-month period with physiological and psychological factors in adults with type 2 diabetes (T2D). Methods Participants included 26 middle-aged (mean age=56.1±10.8 years; 42% women), overweight/obese (mean body mass index (BMI) =37.22±8.78 kg/m2) adults who had been diagnosed with T2D within the past 5 years (mean HbA1c=7.81%). Participants underwent a physical examination, blood tests, and psychological questionnaires, including a self-report questionnaire that assessed the consumption of high glycemic and low glycemic load foods. Participants wore an Actigraph accelerometer for 7 days to assess MVPA and SB. All measures were collected at baseline and at the 6-month follow-up. Spearman rank correlations and regression models were conducted to examine the relationship between activity variables, and the association of activity measures with health outcomes at the 6-month follow-up. Results Decreases in duration of SB bouts and increases in MVPA were associated with decreased levels of HbA1c (p<0.05). Over 50% of the variance in HbA1c levels could be attributed to changes in MVPA and SB. Conclusions MVPA and SB were independently associated with diabetes-related health outcomes. Results suggest that emphasis should be placed on increasing MVPA while decreasing SB, particularly duration of SB bouts. This suggests that even small changes in daily behavior may contribute to improvement in diabetes-related health outcomes. PMID:28405340

Association of physiological and psychological health outcomes with physical activity and sedentary behavior in adults with type 2 diabetes.

PubMed

Garcia, Jeanette M; Cox, Daniel; Rice, David J

2017-01-01

To examine the association between change in moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) over a 6-month period with physiological and psychological factors in adults with type 2 diabetes (T2D). Participants included 26 middle-aged (mean age=56.1±10.8 years; 42% women), overweight/obese (mean body mass index (BMI) =37.22±8.78 kg/m 2 ) adults who had been diagnosed with T2D within the past 5 years (mean HbA1c=7.81%). Participants underwent a physical examination, blood tests, and psychological questionnaires, including a self-report questionnaire that assessed the consumption of high glycemic and low glycemic load foods. Participants wore an Actigraph accelerometer for 7 days to assess MVPA and SB. All measures were collected at baseline and at the 6-month follow-up. Spearman rank correlations and regression models were conducted to examine the relationship between activity variables, and the association of activity measures with health outcomes at the 6-month follow-up. Decreases in duration of SB bouts and increases in MVPA were associated with decreased levels of HbA1c (p<0.05). Over 50% of the variance in HbA1c levels could be attributed to changes in MVPA and SB. MVPA and SB were independently associated with diabetes-related health outcomes. Results suggest that emphasis should be placed on increasing MVPA while decreasing SB, particularly duration of SB bouts. This suggests that even small changes in daily behavior may contribute to improvement in diabetes-related health outcomes.

The Effect of Changes in Physical Activity on Sedentary Behavior: Results From a Randomized Lifestyle Intervention Trial.

PubMed

Siddique, Juned; de Chavez, Peter John; Craft, Lynette L; Freedson, Patty; Spring, Bonnie

2017-07-01

To investigate whether changes in physical activity (PA) have an impact on sedentary behavior (SB) during a lifestyle intervention. Study design was a randomized trial. Participants (n = 204) were individuals with low PA and high sedentary leisure screen time from the Chicago area. Participants were randomized to either increase PA (iPA) or decrease sedentary leisure (dSED). The intervention consisted of decision support, coaching, and financial incentives. For iPA participants, the goal was at least 60 min/d of self-reported moderate-tovigorous-intensity PA (MVPA). For dSED participants the goal was less than 90 min/d of sedentary leisure screen time. Daily accelerometer-based measures of SB and bout-corrected MVPA were obtained. Linear mixed-effects models were fit to estimate the effect of the intervention on MVPA and total SB and to estimate the effect of daily changes in MVPA on daily SB. The iPA participants increased their bout-corrected MVPA by 14 min/d (p < .001) and decreased their total SB by 18 min/d (p < .001). The dSED participants did not significantly change their PA or their total SB. On days when participants exercised, each 10-minute bout of MVPA was associated with a 6-minute decrease in SB on the same day (p < .001). In an intervention study designed to increase MVPA, participants who increase their time spent exercising will obtain much of this time by reducing their SB.

Physical activity intensities in youth: the effect of month of assessment.

PubMed

Silva, Pedro; Seabra, André; Saint-Maurice, Pedro; Soares-Miranda, Luisa; Mota, Jorge

2013-01-01

There is clear evidence that environmental factors play an important role regarding physical activity (PA) and sedentary behaviour (SB) in youth. This short report highlights seasonal differences in the amount and intensities of PA and SB, in Portuguese youth. Three hundred and eighty-seven participants (aged 14.7 ± 1.9 years), 220 girls, used the Actigraph GT1M accelerometer for 7 days (15-second epochs), between January and June in 2008. PA and SB differences were assessed using an ANCOVA. Boys had significantly higher values of PA, with the exception of Light intensity. Girls were significantly more sedentary. PA intensities and SB changed significantly according to gender and month of assessment. SB (Gender F = 16.32, p < 0.001; Month F = 2.95, p < 0.013), Light PA (Gender F = 9.30, p = 0.002; Month F = 8.37, p < 0.001; Gender*Month F = 2.24, p = 0.050), Moderate PA (Gender F = 40.04, p < 0.001), Vigorous PA (Gender F = 32.89, p < 0.001; Month F = 2.56, p = 0.027). Both genders increased PA from winter to summer months and SB decreased. Seasonality in PA intensities and SB suggest that interventions to promote PA and decrease SB must be tailored to take into consideration the month of the year they are going to be implemented and also gender characteristics.

Physical inactivity, but not sedentary behavior or energy intake, is associated with higher fat mass in Latina and African American girls.

PubMed

McClain, Arianna D; Hsu, Ya-Wen; Belcher, Britni R; Nguyen-Rodriguez, Selena; Weigensberg, Marc; Spruijt-Metz, Donna

2011-01-01

Minority girls are disproportionately affected by overweight and obesity. The independent effects of physical activity (PA), sedentary behavior (SB), and diet are not well understood. This study examined the individual influences of PA, SB and diet on fat mass in Latina and African American (AA) girls, aged 8-11. Baseline data from a longitudinal cohort study in minority girls is presented. Multiple linear regression analysis assessed the effects of PA, SB, and energy intake on fat mass, adjusting for lean mass, age, Tanner stage and ethnicity. Participants were 53 Latina and AA girls (77% Latina; M age=9.8 +/- .9; M(BMI%)=80.8 +/- 23.1). Moderate-to-vigorous physical activity (MVPA) by accelerometry (beta= -.13, P<.01) and lean mass (beta=.69, P<.001) were associated with fat mass (Model R2=.63; P<.0001). MVPA by 3-day-physical-activity-recall (beta=-.04, P=.01) and lean mass (beta=.75, P<.001) were associated with fat mass (Model R2=.61; P<.0001). SB and energy intake were not associated with fat mass in any model. Using both objective and subjective measures of PA, MVPA, but not SB or diet, was associated with higher fat mass in Latina and AA girls, independent of lean mass, age, Tanner stage, and ethnicity. Prospective studies are needed to clarify the differential impact of diet and activity levels on adiposity in this population.

Validation and Comparison of Accelerometers Worn on the Hip, Thigh, and Wrists for Measuring Physical Activity and Sedentary Behavior.

PubMed

Montoye, Alexander H K; Pivarnik, James M; Mudd, Lanay M; Biswas, Subir; Pfeiffer, Karin A

2016-01-01

Recent evidence suggests that physical activity (PA) and sedentary behavior (SB) exert independent effects on health. Therefore, measurement methods that can accurately assess both constructs are needed. To compare the accuracy of accelerometers placed on the hip, thigh, and wrists, coupled with machine learning models, for measurement of PA intensity category (SB, light-intensity PA [LPA], and moderate- to vigorous-intensity PA [MVPA]) and breaks in SB. Forty young adults (21 female; age 22.0 ± 4.2 years) participated in a 90-minute semi-structured protocol, performing 13 activities (three sedentary, 10 non-sedentary) for 3-10 minutes each. Participants chose activity order, duration, and intensity. Direct observation (DO) was used as a criterion measure of PA intensity category, and transitions from SB to a non-sedentary activity were breaks in SB. Participants wore four accelerometers (right hip, right thigh, and both wrists), and a machine learning model was created for each accelerometer to predict PA intensity category. Sensitivity and specificity for PA intensity category classification were calculated and compared across accelerometers using repeated measures analysis of variance, and the number of breaks in SB was compared using repeated measures analysis of variance. Sensitivity and specificity values for the thigh-worn accelerometer were higher than for wrist- or hip-worn accelerometers, > 99% for all PA intensity categories. Sensitivity and specificity for the hip-worn accelerometer were 87-95% and 93-97%. The left wrist-worn accelerometer had sensitivities and specificities of > 97% for SB and LPA and 91-95% for MVPA, whereas the right wrist-worn accelerometer had sensitivities and specificities of 93-99% for SB and LPA but 67-84% for MVPA. The thigh-worn accelerometer had high accuracy for breaks in SB; all other accelerometers overestimated breaks in SB. Coupled with machine learning modeling, the thigh-worn accelerometer should be considered when objectively assessing PA and SB.

Research Centre for the Study of the Rogue Waves

NASA Astrophysics Data System (ADS)

Shamin, Roman

2013-04-01

In 2012, in Sakhalin (Russia) was established Research Center for the Study of the Rogue Waves. This center unites many known scientists, who study rogue waves. The center is founded by the following scientific organizations: - The Institute of Marine Geology and Geophysics of FEB RAS - The Far Eastern Federal University - Special Research Bureau for Automation of Marine Researches of FEB RAS - The Institute of Applied Physics of RAS - Shirshov Institute of Oceanology of RAS Heads this center Dr. Roman V. Shamin (Russia). Topics projects: - Probability of emergence of rogue waves - Finding of the sites of the Ocean most dangerous from the point of view of rogue waves - Assessment of risk of dangerous impact of rogue waves - and many others... Our Center is open for new participants from all countries. Our Centre have web-site: roguewaves.ru For contacts: center@roguewaves.ru (Dr. Roman Shamin)

First results of registering ionospheric disturbances obtained with SibNet network of GNSS receivers in active space experiments

NASA Astrophysics Data System (ADS)

Ishin, Artem; Perevalova, Natalia; Voeykov, Sergey; Khakhinov, Vitaliy

2017-12-01

Global and regional networks of GNSS receivers have been successfully used for geophysical research for many years; the number of continuous GNSS stations in the world is steadily growing. The article presents the first results of the use of a new regional network of GNSS stations (SibNet) in active space experiments. The Institute of Solar-Terrestrial Physics of Siberian Branch of Russian Academy of Sciences (ISTP SB RAS) has established this network in the South Baikal region. We describe in detail SibNet, characteristics of receivers in use, parameters of antennas and methods of their installation. We also present the general structure of observation site and the plot of coverage of the receiver operating zone at 50-55° latitudes by radio paths. It is shown that the selected location of receivers allows us to detect ionospheric irregularities of various scales. The purpose of the active space experiments was to reveal and record parameters of the ionospheric irregu larities caused by effects from jet streams of Progress cargo spacecraft. The mapping technique enabled us to identify weak, vertically localized ionospheric irregularities and associate them with the Progress spacecraft engine impact. Thus, it has been shown that SibNet deployed in the Southern Baikal region is an effective instrument for monitoring ionospheric conditions.

Sb-Based n- and p-Channel Heterostructure FETs for High-Speed, Low-Power Applications

DTIC Science & Technology

2008-07-01

Laboratory are presented. 2. InAlSb/InAs HEMTs The HEMT material was grown by solid-source molecu- lar beam epitaxy (MBE) on a semi-insulating (100) GaAs...and S.Y. Lin, “Strained quantum well modulation-doped InGaSb/AlGaSb struc- tures grown by molecular beam epitaxy ,” J. Electron. Mater., vol.22, no.3...where he majored in solid state physics and researched growth by molecular - beam epitaxy (MBE) of certain compound semiconductor ma- terials. Since

Social and physical environmental correlates of adults' weekend sitting time and moderating effects of retirement status and physical health.

PubMed

Van Holle, Veerle; McNaughton, Sarah A; Teychenne, Megan; Timperio, Anna; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Salmon, Jo

2014-09-19

Emerging research suggests that prolonged sedentary behaviour (SB) is detrimental to health. Changes in SB patterns are likely to occur during particular life stages, for example at retirement age (55-65-year-old). Evidence on socio-ecological SB correlates is scarce and inconsistent in this age group. Moreover, the influence of socio-ecological correlates may vary depending on health and retirement status. This study examined social and environment correlates of overall weekend day sitting among adults at or approaching retirement age, and moderating effects of perceived physical health and retirement status. Baseline data from the Wellbeing, Eating and Exercise for a Long Life study in 2839 Australian adults (55-65-year-old) were analysed. Participants self-reported proximal social factors, neighbourhood social and physical environment, physical health and retirement status. MLwiN multilevel regression analyses were conducted. In the multivariable model, only social support from friends/colleagues to discourage sitting (B = -0.891; p = 0.036) was associated with overall weekend day sitting. No moderation of retirement status, nor physical health were found in the multivariable results. Results from this study suggest the importance of social factors in relation to weekend day sitting among 55-65-year-old adults. Health promotion initiatives in this age group should pay special attention to enhancing social interaction opportunities. Moreover, findings suggest that SB-specific correlates may need to be examined in future research.

Spectral composition of inhomogeneities of intensity of laser beam translucent the supersonic jet near the nozzle

NASA Astrophysics Data System (ADS)

Marakasov, Dmitri A.; Melnikov, Nikolai G.; Sazanovich, Valentina M.; Tsvyk, Ruvim Sh.; Shesternin, Andrei N.

2014-11-01

The analysis of results of experiments on laser transillumination of the flooded supersonic jet on the wind tunnel of Institute of theoretical and applied mechanics SB RAS is fulfilled. The time spectra of fluctuations of the received power at different values of pressure in the chamber as well as the transformation of the spectra for the initial part of the jet with increasing distance from the nozzle are discussed. The change in the slope of the high-frequency part of the spectrum when lifting beam above the nozzle is demonstrated. Local maxima of the spectral density at frequencies corresponding to the discrete frequencies of acoustic tones generated by the stream are found.

Model and on-orbit study of the International space station contamination processes by jets of its orientation thrusters

NASA Astrophysics Data System (ADS)

Yarygin, V. N.; Gerasimov, Yu I.; Krylov, A. N.; Prikhodko, V. G.; Skorovarov, A. Yu; Yarygin, I. V.

2017-11-01

The main objective of this paper is to describe the current state of research for the problem of the International Space Station contamination by plumes of its orientation thrusters. Results of experiments carried out at the Institute of Thermophysics SB RAS modeling space vehicles orientation thruster’s plumes are presented and experimental setup is discussed. A novel approach to reduction of contamination by thrusters with the help of special gas-dynamic protective devices mounted at the exit part of the nozzle is suggested. The description and results of on-orbit experiment at the International Space Station are given. Results show good agreement for model and on-orbit experiments validating our approach.

Physics of bandgap formation in Cu-Sb-Se based novel thermoelectrics: the role of Sb valency and Cu d levels.

PubMed

Do, Dat; Ozolins, Vidvuds; Mahanti, S D; Lee, Mal-Soon; Zhang, Yongsheng; Wolverton, C

2012-10-17

In this paper we discuss the results of ab initio electronic structure calculations for Cu(3)SbSe(4) (Se4) and Cu(3)SbSe(3) (Se3), two narrow bandgap semiconductors of thermoelectric interest. We find that Sb is trivalent in both the compounds, in contrast to a simple nominal valence (ionic) picture which suggests that Sb should be 5 + in Se4. The gap formation in Se4 is quite subtle, with hybridization between Sb 5s and the neighboring Se 4s, 4p orbitals, position of Cu d states, and non-local exchange interaction, each playing significant roles. Thermopower calculations show that Se4 is a better p-type system. Our theoretical results for Se4 agree very well with recent experimental results obtained by Skoug et al (2011 Sci. Adv. Mater. 3 602).

A National Survey of Physical Activity and Sedentary Behavior of Chinese City Children and Youth Using Accelerometers

ERIC Educational Resources Information Center

Wang, Chao; Chen, Peijie; Zhuang, Jie

2013-01-01

Purpose: The purpose of this study was to objectively assess levels of physical activity (PA) and sedentary behavior (SB) of Chinese city children and youth aged 9 to 17 years old using accelerometers and to examine their differences by gender, age, grade, and weight status. Method: The PA and SB of 2,163 students in 4th grade through 11th grade…

Does duration of physical activity bouts matter for adiposity and metabolic syndrome? A cross-sectional study of older British men.

PubMed

Jefferis, Barbara J; Parsons, Tessa J; Sartini, Claudio; Ash, Sarah; Lennon, Lucy T; Wannamethee, S Goya; Lee, I-Min; Whincup, Peter H

2016-03-15

Older adults have low physical activity(PA) and high sedentary behaviour(SB) levels. We investigate how total volume and specific patterns of moderate to vigorous PA(MVPA), light PA(LPA) and SB are related to adiposity and metabolic syndrome (MS). Then, with reference to physical activity guidelines which encourage MVPA in bouts > =10 min and avoiding "long" sedentary bouts, we investigate whether accumulating PA and SB in bouts of different defined durations are differently associated with these outcomes. Cross-sectional study of men (71-91 years) recruited in UK primary care centres. Nurses made physical measures (weight, height, bio-impedance, blood pressure) and took fasting blood samples. 1528/3137 (49%) surviving men had ≥3 valid days (≥600 min) accelerometer data. 450 men with pre-existing chronic disease were excluded. 1009/1078 (93.6%) had complete covariate data. Men (n = 1009, mean age 78.5(SD 4.7) years) spent 612(SD 83), 202(SD 64) and 42(SD 33) minutes in SB, LIPA and MVPA respectively. Each additional 30 min/day of SB and MVPA were associated with 0.32 (95% CI 0.23, 0.40)Kg/m(2) higher Body Mass Index (BMI) and -0.72(-0.93, -0.51) lower BMI Kg/m(2) respectively. Patterns for waist circumference (WC), fat mass index (FMI), fasting insulin and MS were similar. MVPA in bouts lasting <10 min or ≥10 min duration were not associated differently with outcomes. In models adjusted for total MVPA, each minute accumulated in SB bouts lasting 1-15 min was associated with lower BMI -0.012 kg/m(2), WC -0.029 cm, and OR 0.989 for MS (all p < 0.05), and coefficients for LPA bouts 1-9 min were very similar in separate models adjusted for total MVPA. Minutes accumulated in SB bouts 1-15 min and LPA bouts 1-9 min were correlated, r = 0.62. Objectively measured MVPA, LPA and SB were all associated with lower adiposity and metabolic risk. The beneficial associations of LPA are encouraging for older adults for whom initiating MVPA and maintaining bouts lasting ≥10 min may be particularly challenging. Findings that short bouts of LPA (1-9 min) and SB (1-15 min), but that all MVPA, not just MVPA accumulated in bouts ≥10 min were associated with lower adiposity and better metabolic health could help refine older adult PA guidelines.

Crystal growth and characterization of bulk Sb2Te3 topological insulator

NASA Astrophysics Data System (ADS)

Sultana, Rabia; Gurjar, Ganesh; Patnaik, S.; Awana, V. P. S.

2018-04-01

The Sb2Te3 crystals are grown using the conventional self flux method via solid state reaction route, by melting constituent elements (Sb and Te) at high temperature (850 °C), followed by slow cooling (2 °C/h). As grown Sb2Te3 crystals are analysed for various physical properties by x-ray diffraction (XRD), Raman Spectroscopy, Scanning Electron Microscopy (SEM) coupled with Energy Dispersive x-ray Spectroscopy (EDAX) and electrical measurements under magnetic field (6 Tesla) down to low temperature (2.5 K). The XRD pattern revealed the growth of synthesized Sb2Te3 sample along (00l) plane, whereas the SEM along with EDAX measurements displayed the layered structure with near stoichiometric composition, without foreign contamination. The Raman scattering studies displayed known ({{{{A}}}1{{g}}}1, {{{{E}}}{{g}}}2 and {{{{A}}}1{{g}}}2) vibrational modes for the studied Sb2Te3. The temperature dependent electrical resistivity measurements illustrated the metallic nature of the as grown Sb2Te3 single crystal. Further, the magneto—transport studies represented linear positive magneto-resistance (MR) reaching up to 80% at 2.5 K under an applied field of 6 Tesla. The weak anti localization (WAL) related low field (±2 Tesla) magneto-conductance at low temperatures (2.5 K and 20 K) has been analysed and discussed using the Hikami—Larkin—Nagaoka (HLN) model. Summarily, the short letter reports an easy and versatile method for crystal growth of bulk Sb2Te3 topological insulator (TI) and its brief physical property characterization.

Reliability and Validity of 2 Self-Report Measures to Assess Sedentary Behavior in Older Adults.

PubMed

Gennuso, Keith P; Matthews, Charles E; Colbert, Lisa H

2015-05-01

The purpose of this study was to examine the reliability and validity of 2 currently available physical activity surveys for assessing time spent in sedentary behavior (SB) in older adults. Fifty-eight adults (≥65 years) completed the Yale Physical Activity Survey for Older Adults (YPAS) and Community Health Activities Model Program for Seniors (CHAMPS) before and after a 10-day period during which they wore an ActiGraph accelerometer (ACC). Intraclass correlation coefficients (ICC) examined test-retest reliability. Overall percent agreement and a kappa statistic examined YPAS validity. Lin's concordance correlation, Pearson correlation, and Bland-Altman analysis examined CHAMPS validity. Both surveys had moderate test-retest reliability (ICC: YPAS = 0.59 (P < .001), CHAMPS = 0.64 (P < .001)) and significantly underestimated SB time. Agreement between YPAS and ACC was low (κ = -0.0003); however, there was a linear increase (P < .01) in ACC-derived SB time across YPAS response categories. There was poor agreement between ACC-derived SB and CHAMPS (Lin's r = .005; 95% CI, -0.010 to 0.020), and no linear trend across CHAMPS quartiles (P = .53). Neither of the surveys should be used as the sole measure of SB in a study; though the YPAS has the ability to rank individuals, providing it with some merit for use in correlational SB research.

Buried homojunction in CdS/Sb2Se3 thin film photovoltaics generated by interfacial diffusion

NASA Astrophysics Data System (ADS)

Zhou, Ying; Li, Yang; Luo, Jiajun; Li, Dengbing; Liu, Xinsheng; Chen, Chao; Song, Huaibing; Ma, Jingyuan; Xue, Ding-Jiang; Yang, Bo; Tang, Jiang

2017-07-01

Antimony selenide (Sb2Se3) emerges as a very promising non-toxic absorber material for thin film photovoltaics, and most of the devices, either in the superstrate or substrate configuration, employed CdS as the buffer layer. Due to the peculiar one-dimensional crystal structure of Sb2Se3, severe interfacial diffusion would be expected. In this letter, the interfacial diffusion in CdS/Sb2Se3 photovoltaics was carefully characterized from a combined material and device physics characterization. The results indicated that a buried homojunction located deep inside the Sb2Se3 absorber layer due to Cd diffusion, instead of the apparent CdS/Sb2Se3 heterojunction, dictated charge separation and device performance in Sb2Se3 thin film solar cells. Cd diffusion converted p-type Sb2Se3 into n-type by introducing a donor level with an activation energy of 0.22 eV. Our studies deepen the understanding of Sb2Se3 photovoltaics and shed light on their further performance optimization.

Classification Accuracy of a Wearable Activity Tracker for Assessing Sedentary Behavior and Physical Activity in 3-5-Year-Old Children.

PubMed

Byun, Wonwoo; Lee, Jung-Min; Kim, Youngwon; Brusseau, Timothy A

2018-03-26

This study examined the accuracy of the Fitbit activity tracker (FF) for quantifying sedentary behavior (SB) and varying intensities of physical activity (PA) in 3-5-year-old children. Twenty-eight healthy preschool-aged children (Girls: 46%, Mean age: 4.8 ± 1.0 years) wore the FF and were directly observed while performing a set of various unstructured and structured free-living activities from sedentary to vigorous intensity. The classification accuracy of the FF for measuring SB, light PA (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) was examined calculating Pearson correlation coefficients (r), mean absolute percent error (MAPE), Cohen's kappa ( k ), sensitivity (Se), specificity (Sp), and area under the receiver operating curve (ROC-AUC). The classification accuracies of the FF (ROC-AUC) were 0.92, 0.63, 0.77 and 0.92 for SB, LPA, MVPA and TPA, respectively. Similarly, values of kappa, Se, Sp and percentage of correct classification were consistently high for SB and TPA, but low for LPA and MVPA. The FF demonstrated excellent classification accuracy for assessing SB and TPA, but lower accuracy for classifying LPA and MVPA. Our findings suggest that the FF should be considered as a valid instrument for assessing time spent sedentary and overall physical activity in preschool-aged children.

The NM23-H1/H2 homolog NDK-1 is required for full activation of Ras signaling in C. elegans

PubMed Central

Masoudi, Neda; Fancsalszky, Luca; Pourkarimi, Ehsan; Vellai, Tibor; Alexa, Anita; Reményi, Attila; Gartner, Anton; Mehta, Anil; Takács-Vellai, Krisztina

2013-01-01

The group I members of the Nm23 (non-metastatic) gene family encode nucleoside diphosphate kinases (NDPKs) that have been implicated in the regulation of cell migration, proliferation and differentiation. Despite their developmental and medical significance, the molecular functions of these NDPKs remain ill defined. To minimize confounding effects of functional compensation between closely related Nm23 family members, we studied ndk-1, the sole Caenorhabditis elegans ortholog of group I NDPKs, and focused on its role in Ras/mitogen-activated protein kinase (MAPK)-mediated signaling events during development. ndk-1 inactivation leads to a protruding vulva phenotype and affects vulval cell fate specification through the Ras/MAPK cascade. ndk-1 mutant worms show severe reduction of activated, diphosphorylated MAPK in somatic tissues, indicative of compromised Ras/MAPK signaling. A genetic epistasis analysis using the vulval induction system revealed that NDK-1 acts downstream of LIN-45/Raf, but upstream of MPK-1/MAPK, at the level of the kinase suppressors of ras (KSR-1/2). KSR proteins act as scaffolds facilitating Ras signaling events by tethering signaling components, and we suggest that NDK-1 modulates KSR activity through direct physical interaction. Our study reveals that C. elegans NDK-1/Nm23 influences differentiation by enhancing the level of Ras/MAPK signaling. These results might help to better understand how dysregulated Nm23 in humans contributes to tumorigenesis. PMID:23900546

Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor.

PubMed

Zhang, Shao-Ling; Moini, Babak; Ingelfinger, Julie R

2004-06-01

Although both the renin angiotensin system (RAS) and the paired homeobox 2 gene (Pax-2) seem critically important in renal organogenesis, whether and how they might interact has not been addressed. The present study asked whether a link between the RAS and Pax-2 exists in fetal renal cells, speculating that such an interaction, if present, might influence renal development. Embryonic kidney explants and embryonic renal cells (mouse late embryonic mesenchymal epithelial cells [MK4] and mouse early embryonic mesenchymal fibroblasts [MK3]) were used. Pax-2 protein and Pax-2 mRNA were detected by immunofluorescence, Western blot, reverse transcription-PCR, and real-time PCR. Angiotensin II (AngII) upregulated Pax-2 protein and Pax-2 mRNA expression via the AngII type 2 (AT(2)) receptor in MK4 but not in MK3 cells. The stimulatory effect of AngII on Pax-2 gene expression could be blocked by PD123319 (AT(2) inhibitor), AG 490 (a specific Janus kinase 2 inhibitor), and genistein (a tyrosine kinase inhibitor) but not by losartan (AT(1) inhibitor), SB203580 (specific p38 mitogen-activated protein kinase inhibitor), PD98059 (specific MEK inhibitor), SP600125 (JNK inhibitor), and diphenyleneiodonium chloride (an NADPH oxidase inhibitor). Moreover, embryonic kidney explants in culture confirmed that AngII upregulates Pax-2 gene expression via the AT(2) receptor. These studies demonstrate that the stimulatory effect of AngII on Pax-2 gene expression is mediated, at least in part, via the Janus kinase 2/signal transducers and activators of transcription signaling transduction pathway, suggesting that RAS and Pax-2 interactions may be important in renal development.

Mothers’ perceptions of the UK physical activity and sedentary behaviour guidelines for the early years (Start Active, Stay Active): a qualitative study

PubMed Central

Bentley, Georgina F; Jago, Russell; Turner, Katrina M

2015-01-01

Objectives Higher levels of physical activity (PA) during early childhood have been associated with improved health outcomes, whereas sedentary behaviour (SB) has been associated with poorer health outcomes in children. In 2011, the UK produced guidelines for PA and SB in children under 5 years. Mothers have been identified as key influences in young children's PA and SB. The aim of this study was to use in-depth interviews with mothers of preschool children to examine attitudes to the guidance. Design Qualitative study using one-to-one, semistructured interviews; Data were analysed thematically using a framework approach. Setting Mothers were recruited from preschools, nurseries, and mother and toddler groups located in four areas of varying socioeconomic status within Bristol, UK. Participants 24 mothers who were considered the main or joint carer for a preschool child who was at least 2 years of age but had not yet started formal schooling. Results Mothers are not aware of the UK PA and SB guidelines for the early years. They believe that their child achieves the guideline targets for PA and SB and therefore, they do not believe these quidelines are relevant to them. Mothers feel that an increase in PA and reduction in SB (especially screen-viewing) would cause stress for mothers. Mothers found defining and quantifying PA and SB in their preschool child problematic. Conclusions As mothers do not identify with the need to increase PA or reduce SB in their child, awareness of the guidelines alone is unlikely to initiate behaviour change. Information on how mothers can make a more accurate assessment of their preschool child's PA and SB levels, and information about the benefits of increased PA and reduced SB should be provided alongside the guideline targets. Clear messages need to be developed that reframe the guidelines into pragmatic and usable targets. PMID:26351186

Inclusion of Linearized Moist Physics in Nasa's Goddard Earth Observing System Data Assimilation Tools

NASA Technical Reports Server (NTRS)

Holdaway, Daniel; Errico, Ronald; Gelaro, Ronaldo; Kim, Jong G.

2013-01-01

Inclusion of moist physics in the linearized version of a weather forecast model is beneficial in terms of variational data assimilation. Further, it improves the capability of important tools, such as adjoint-based observation impacts and sensitivity studies. A linearized version of the relaxed Arakawa-Schubert (RAS) convection scheme has been developed and tested in NASA's Goddard Earth Observing System data assimilation tools. A previous study of the RAS scheme showed it to exhibit reasonable linearity and stability. This motivates the development of a linearization of a near-exact version of the RAS scheme. Linearized large-scale condensation is included through simple conversion of supersaturation into precipitation. The linearization of moist physics is validated against the full nonlinear model for 6- and 24-h intervals, relevant to variational data assimilation and observation impacts, respectively. For a small number of profiles, sudden large growth in the perturbation trajectory is encountered. Efficient filtering of these profiles is achieved by diagnosis of steep gradients in a reduced version of the operator of the tangent linear model. With filtering turned on, the inclusion of linearized moist physics increases the correlation between the nonlinear perturbation trajectory and the linear approximation of the perturbation trajectory. A month-long observation impact experiment is performed and the effect of including moist physics on the impacts is discussed. Impacts from moist-sensitive instruments and channels are increased. The effect of including moist physics is examined for adjoint sensitivity studies. A case study examining an intensifying Northern Hemisphere Atlantic storm is presented. The results show a significant sensitivity with respect to moisture.

Effect of Sb on physical properties and microstructures of laser nano/amorphous-composite film

NASA Astrophysics Data System (ADS)

Li, Jia-Ning; Gong, Shui-Li; Sun, Mei; Shan, Fei-Hu; Wang, Xi-Chang; Jiang, Shuai

2013-11-01

A nano/amorphous-composite film was fabricated by laser cladding (LC) of the Co-Ti-B4C-Sb mixed powders on a TA15 alloy. Such film mainly consisted of Ti-Al, Co-Ti, Co-Sb intermetallics, TiC, TiB2, TiB, and the amorphous phases. Experimental results indicated that the crystal systems of TiB2 (hexagonal)/TiC (cubic) and Sb (rhombohedral) played important role on the formation of such film. Due to the mismatch of these crystals systems and mutual immiscibility of the metallic components, Sb was not incorporated in TiB2/TiC, but formed separate nuclei during the film growth. Thus, the growth of TiB2/TiC was stopped by the Sb nucleus in such LC molten pool, so as to form the nanoscale particles.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment.

PubMed

Bringolf-Isler, Bettina; Mäder, Urs; Dössegger, Alain; Hofmann, Heidi; Puder, Jardena J; Braun-Fahrländer, Charlotte; Kriemler, Susi

2015-03-01

We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10-15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

Physical activity ameliorates the association between sedentary behavior and cardiometabolic risk among inpatients with schizophrenia: A comparison versus controls using accelerometry.

PubMed

Stubbs, Brendon; Chen, Li-Jung; Chung, Ming-Shun; Ku, Po-Wen

2017-04-01

A lack of clarity exists regarding the relationship between objectively measured physical activity (PA) and sedentary behavior (SB) and cardiometabolic outcomes in people with schizophrenia. We conducted a large study investigating the independent relationships of PA and SB among inpatients with schizophrenia versus healthy controls (HCs). A cross sectional study including 199 inpatients with schizophrenia (mean age 44.0years, mean illness duration 23.8years) versus 60 age/sex/body mass index matched HCs. Participants wore accelerometers for 7days to capture SB and daily steps. Cardiometabolic outcomes included blood pressure, fasting blood glucose (FBG), triglycerides, high-density lipoprotein cholesterol (HDL-C) and waist circumference (WC). Multivariate regression analyses adjusting for multiple confounders were undertaken. Compared to HCs, patients engaged in more sedentary behavior and less daily steps versus HCs (p<0.001). Patients with higher levels of SB (n=89) had increased fasting glucose compared to patients with low levels of SB (105.2 vs. 96.3mg/dl, p<0.05). In the multivariate analysis, sedentary behavior was associated with higher FBG (β = .146, p=.041) but this was ameliorated when daily steps were inserted in to the model (β = .141, p=.059). In the final model, higher daily steps were associated with more favorable HDL-C (β=-.226, p=.004), independent of SB and other confounders. Our data suggest that higher than while sedentary behavior is related to worse fasting glucose, this relationship is attenuated when PA is taken into account. Physical activity is also associated with favorable HDL-C. Interventions targeting replacing sedentary behavior with PA may improve metabolic risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical Activity and Sedentary Behavior Patterns Before and During Pregnancy in a Multi-ethnic Sample of Asian Women in Singapore.

PubMed

Padmapriya, N; Shen, Liang; Soh, Shu-E; Shen, Zhe; Kwek, Kenneth; Godfrey, Keith M; Gluckman, Peter D; Chong, Yap-Seng; Saw, Seang-Mei; Müller-Riemenschneider, Falk

2015-11-01

To describe physical activity (PA) and sedentary behavior (SB) patterns before and during pregnancy among Chinese, Malay and Indian women. In addition, to investigate determinants of change in PA and SB during pregnancy. The Growing Up in Singapore Towards healthy Outcomes cohort recruited first trimester pregnant women. PA and SB (sitting time and television time) before and during pregnancy were assessed as a part of an interview questionnaire at weeks 26-28 gestational clinic visit. Total energy expenditure (TEE) on PA and time in SB were calculated. Determinants of change in PA and SB were investigated using multiple logistic regression analysis. PA and SB questions were answered by 94 % (n = 1171) of total recruited subjects. A significant reduction in TEE was observed from before to during pregnancy [median 1746.0-1039.5 metabolic equivalent task (MET) min/week, p < 0.001]. The proportion of women insufficiently active (<600 MET-min/week) increased from 19.0 to 34.1 % (p <0.001). Similarly, sitting time (median 56.0-63.0 h/week, p < 0.001) and television time (mean 16.1-16.7 h/week, p = 0.01) increased. Women with higher household income, lower level of perceived health, nausea/vomiting during pregnancy and higher level of pre-pregnancy PA were more likely to reduce PA. Women with children were less likely to reduce PA. Women reporting nausea/vomiting and lower level of pre-pregnancy sitting time were more likely to increase sitting time. Participants substantially reduced PA and increased SB by 26-28 weeks of pregnancy. Further research is needed to better understand determinants of change in PA and SB and develop effective health promotion strategies.

Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal subarachnoid hemorrhage: evidence from accelerometer-based activity monitoring.

PubMed

Harmsen, Wouter J; Ribbers, Gerard M; Heijenbrok-Kal, Majanka H; Bussmann, Johannes B J; Sneekes, Emiel M; Khajeh, Ladbon; van Kooten, Fop; Neggers, Sebastian J C M M; van den Berg-Emons, Rita J

2017-11-23

Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life-threatening stroke. Because survivors may be at increased risk for inactive and sedentary lifestyles, this study evaluates physical activity (PA) and sedentary behavior (SB) in the chronic phase after a-SAH. PA and SB were objectively measured at six months post a-SAH with an accelerometer-based activity monitor, with the aim to cover three consecutive weekdays. Total time spent in PA (comprising walking, cycling, running and non-cyclic movement) and SB (comprising sitting and lying) was determined. Also, in-depth analyses were performed to determine the accumulation and distribution of PA and SB throughout the day. Binary time series were created to determine the mean bout length and the fragmentation index. Measures of PA and SB in persons with a-SAH were compared to those in sex- and age-matched healthy controls. The 51 participants comprised 33 persons with a-SAH and 18 controls. None of the participants had signs of paresis or spasticity. Persons with a-SAH spent 105 min/24 h being physically active, which was 35 min/24 h less than healthy controls (p = 0.005). For PA, compared with healthy controls, the mean bout length was shorter in those with a-SAH (12.0 vs. 13.5 s, p = 0.006) and the fragmentation index was higher (0.053 vs. 0.041, p < 0.001). Total sedentary time during waking hours showed no significant difference between groups (514 min vs. 474 min, p = 0.291). For SB, the mean bout length was longer in persons with a-SAH (122.3 vs. 80.5 s, p = 0.024), whereas there was no difference in fragmentation index between groups (0.0032 vs 0.0036, p = 0.396). Persons with a-SAH are less physically active, they break PA time into shorter periods, and SB periods last longer compared to healthy controls. Since inactive lifestyles and prolonged uninterrupted periods of SB are independent risk factors for poor cardiovascular health, interventions seem necessary and should target both PA and SB. Dutch registry number: NTR 2085.

Variational fine-grained data assimilation schemes for atmospheric chemistry transport and transformation models

NASA Astrophysics Data System (ADS)

Penenko, Alexey; Penenko, Vladimir; Tsvetova, Elena

2015-04-01

The paper concerns data assimilation problem for an atmospheric chemistry transport and transformation models. Data assimilation is carried out within variation approach on a single time step of the approximated model. A control function is introduced into the model source term (emission rate) to provide flexibility to adjust to data. This function is evaluated as the minimum of the target functional combining control function norm to a misfit between measured and model-simulated analog of data. This provides a flow-dependent and physically-plausible structure of the resulting analysis and reduces the need to calculate model error covariance matrices that are sought within conventional approach to data assimilation. Extension of the atmospheric transport model with a chemical transformations module influences data assimilation algorithms performance. This influence is investigated with numerical experiments for different meteorological conditions altering convection-diffusion processes characteristics, namely strong, medium and low wind conditions. To study the impact of transformation and data assimilation, we compare results for a convection-diffusion model (without data assimilation), convection-diffusion with assimilation, convection-diffusion-reaction (without data assimilation) and convection-diffusion-reaction-assimilation models. Both high dimensionalities of the atmospheric chemistry models and a real-time mode of operation demand for computational efficiency of the algorithms. Computational issues with complicated models can be solved by using a splitting technique. As the result a model is presented as a set of relatively independent simple models equipped with a kind of coupling procedure. With regard to data assimilation two approaches can be identified. In a fine-grained approach data assimilation is carried out on the separate splitting stages [1,2] independently on shared measurement data. The same situation arises when constructing a hybrid model out of two models each having its own assimilation scheme. In integrated schemes data assimilation is carried out with respect to the split model as a whole. First approach is more efficient from computational point of view, for in some important cases it can be implemented without iterations [2]. Its shortcoming is that control functions in different part of the model are adjusted independently thus having less evident physical sense. With the aid of numerical experiments we compare the two approaches. Work has been partially supported by COST Action ES1004 STSM Grants #16817 and #21654, RFBR 14-01-31482 mol a and 14-01-00125, Programmes # 4 Presidium RAS and # 3 MSD RAS, integration projects SB RAS #8 and #35. References: [1] V. V. Penenko Variational methods of data assimilation and inverse problems for studying the atmosphere, ocean, and environment Num. Anal. and Appl., 2009 V 2 No 4, 341-351. [2] A.V. Penenko and V.V. Penenko. Direct data assimilation method for convection-diffusion models based on splitting scheme. Computational technologies, 19(4):69-83, 2014.

Synthesis and Characteristics of HgCdSe for IR Detection

DTIC Science & Technology

2014-03-11

Photoelectron Spectroscopy Study of Oxide Removal Using Atomic Hydrogen for Large-Area II–VI Material Growth, Journal of Electronic Materials...Workshop on the Physics and Chemistry of II-VI Materials, Chicago IL (October 1-3, 2013) “Use of Atomic Hydrogen to Prepare GaSb(211)B and GaSb(100...Workshop on the Physics and Chemistry of II-VI Materials, Chicago IL (October, 2011) "Xray photoelectron spectroscopy study of oxide removal using

Development and validation of a new self-report instrument for measuring sedentary behaviors and light-intensity physical activity in adults.

PubMed

Barwais, Faisal Awad; Cuddihy, Thomas F; Washington, Tracy; Tomson, L Michaud; Brymer, Eric

2014-08-01

Low levels of physical activity and high levels of sedentary behavior (SB) are major public health concerns. This study was designed to develop and validate the 7-day Sedentary (S) and Light Intensity Physical Activity (LIPA) Log (7-day SLIPA Log), a self-report measure of specific daily behaviors. To develop the log, 62 specific SB and LIPA behaviors were chosen from the Compendium of Physical Activities. Face-to-face interviews were conducted with 32 sedentary volunteers to identify domains and behaviors of SB and LIPA. To validate the log, a further 22 sedentary adults were recruited to wear the GT3x for 7 consecutive days and nights. Pearson correlations (r) between the 7-day SLIPA Log and GT3x were significant for sedentary (r = .86, P < .001), for LIPA (r = .80, P < .001). Lying and sitting postures were positively correlated with GT3x output (r = .60 and r = .64, P < .001, respectively). No significant correlation was found for standing posture (r = .14, P = .53).The kappa values between the 7-day SLIPA Log and GT3x variables ranged from 0.09 to 0.61, indicating poor to good agreement. The 7-day SLIPA Log is a valid self-report measure of SB and LIPA in specific behavioral domains.

Physical preparation and optical properties of CuSbS2 nanocrystals by mechanical alloying process

NASA Astrophysics Data System (ADS)

Zhang, Huihui; Xu, Qishu; Tan, Guolong

2016-09-01

CuSbS2 nanocrystals have been synthesized through mechanical alloying Cu, Sb and S elemental powders for 40 hs. The optical spectrum of as-milled CuSbS2 nano-powders demonstrates a direct gap of 1.35 eV and an indirect gap of 0.36 eV, which are similar to that of silicon and reveals the evidence for the indirect semiconductor characterization of CuSbS2. Afterwards, CuSbS2 nanocrystals were capped with trioctylphosphine oxide/trioctylphosphine/pyridine (TOPO/TOP). There appear four sharp absorption peaks within the region of 315 to 355 nm for the dispersion solution containing the capped nanocrystals. The multiple peaks are proposed to be originating from the energy level splitting of 1S electronic state into four discrete sub-levels, where electrons were excited into the conduction band and thus four exciton absorption peaks were produced.

Reliability and Validity of Two Self-report Measures to Assess Sedentary Behavior in Older Adults

PubMed Central

Gennuso, Keith P.; Matthews, Charles E.; Colbert, Lisa H.

2015-01-01

Background The purpose of this study was to examine the reliability and validity of two currently available physical activity surveys for assessing time spent in sedentary behavior (SB) in older adults. Methods Fifty-eight adults (≥65 years) completed the Yale Physical Activity Survey for Older Adults (YPAS) and Community Health Activities Model Program for Seniors (CHAMPS) before and after a 10-day period during which they wore an ActiGraph accelerometer (ACC). Intraclass correlation coefficients (ICC) examined test-retest reliability. Overall percent agreement and a kappa statistic examined YPAS validity. Lin’s concordance correlation, Pearson correlation, and Bland-Altman analysis examined CHAMPS validity. Results Both surveys had moderate test-retest reliability (ICC: YPAS=0.59 (P<0.001), CHAMPS=0.64 (P<0.001)) and significantly underestimated SB time. Agreement between YPAS and ACC was low (κ=−0.0003); however, there was a linear increase (P< 0.01) in ACC-derived SB time across YPAS response categories. There was poor agreement between ACC-derived SB and CHAMPS (Lin’s r=0.005; 95% CI, −0.010 to 0.020), and no linear trend across CHAMPS quartiles (p=0.53). Conclusions Neither of the surveys should be used as the sole measure of SB in a study; though the YPAS has the ability to rank individuals, providing it with some merit for use in correlational SB research. PMID:25110344

Theoretical investigations of electrical transport properties in CoSb3 skutterudites under hydrostatic loadings

DOE PAGES

Hu, Chongze; Ni, Peter; Zhan, Li; ...

2018-01-30

We report that CoSb 3-based skutterudites have been a benchmark mid-temperature thermoelectric material under intensive experimental and theoretical studies for decades. Doping and filling, to the first order, alter the crystal lattice constant of CoSb 3 in the context of “chemical pressure.” In this work, we employed ab initio density functional theory in conjunction with semiclassical Boltzmann transport theory to investigate the mechanical properties and especially how hydrostatic loadings, i.e., “physical pressure,” impact the electronic band structure, Seebeck coefficient, and power factor of pristine CoSb 3. It is found that hydrostatic pressure enlarges the band gap, suppresses the density ofmore » states (DOS) near the valence band edge, and fosters the band convergence between the valley bands and the conduction band minimum (CBM). By contrast, hydrostatic tensile reduces the band gap, increases the DOS near the valence band edge, and diminishes the valley bands near the CBM. Therefore, applying hydrostatic pressure provides an alternative avenue for achieving band convergence to improve thermoelectric properties of N-type CoSb 3, which is further supported by our carrier concentration studies. Lastly, these results provide valuable insight into the further improvement of thermoelectric performance of CoSb 3-based skutterudites via a synergy of physical and chemical pressures.« less

Temporal and Spatial Variability of the Ras Al-Hadd Jet/Front in the Northwest Arabian Sea

NASA Astrophysics Data System (ADS)

Al Shaqsi, Hilal Mohamed Said

Thirteen years of 1.1 km resolution daily satellites remote sensing sea surface temperature datasets (2002-2014), sea surface winds, sea surface height, Argo floats, daily three-hour interval wind datasets, and hourly records of oceanography physical parameters from mooring current meters were processed and analyzed to investigate the dynamics, temporal and spatial variability of the Ras Al-Hadd Jet off the northwest Arabian Sea. Cayula and Cornillon single image edge detection algorithm was used to detect these thermal fronts. The Ras Al-Hadd thermal front was found to have two seasonal peaks. The first peak occurred during the intensified southwest monsoon period (July/August), while the second peak was clearly observed during the transitional period or the Post-Southwest monsoon (September-October). Interannual and intraseasonal variability showed the occurrence of the Ras Al-Hadd thermal fronts in the northwest Arabian Sea. The southwest monsoon winds, the Somalia Current, the East Arabian Current, and the warmer high salinity waters from the Sea of Oman are the main factors influencing the creation of the Ras Al-Hadd Jet. Based on direct observations, current velocity in the Cape Ras Al-Hadd Jet exceeded 120 cms-1, and the wind speed was over 12 ms-1 during the southwest monsoon seasons. The mean width and the mean length of the Jet were approximately 40 km and 260 km, respectively. Neither the winter monsoon, nor the Pre-Southwest monsoon seasons showed signs of the Ras Al-Hadd Jet or fronts in the northwest Arabian Sea.

Development and implementation of the software for visualization and analysis of data geophysical loggers

NASA Astrophysics Data System (ADS)

Gordeev, V. F.; Malyshkov, S. Yu.; Botygin, I. A.; Sherstnev, V. S.; Sherstneva, A. I.

2017-11-01

The general trend of modern ecological geophysics is changing priorities towards rapid assessment, management and prediction of ecological and engineering soil stability as well as developing brand new geophysical technologies. The article describes researches conducted by using multi-canal geophysical logger MGR-01 (developed by IMCES SB RAS), which allows to measure flux density of very low-frequency electromagnetic radiation. It is shown that natural pulsed electromagnetic fields of the earthen lithosphere can be a source of new information on Earth's crust and processes in it, including earthquakes. The device is intended for logging electromagnetic processes in Earth's crust, geophysical exploration, finding structural and lithological inhomogeneities, monitoring the geodynamic movement of Earth's crust, express assessment of seismic hazards. The data is gathered automatically from observation point network in Siberia

FTIR spectrometer with 30 m optical cell and its applications to the sensitive measurements of selective and nonselective absorption spectra

NASA Astrophysics Data System (ADS)

Ponomarev, Yu. N.; Solodov, A. A.; Solodov, A. M.; Petrova, T. M.; Naumenko, O. V.

2016-07-01

A description of the spectroscopic complex at V.E. Zuev Institute of Atmospheric Optics, SB RAS, operating in a wide spectral range with high threshold sensitivity to the absorption coefficient is presented. Measurements of weak lines and nonselective spectra of CO2 and H2O were performed based on the built setup. As new application of this setup, positions and intensities of 152 weak lines of H2O were measured between 2400 and 2560 cm-1 with threshold sensitivity of 8.6×10-10 cm-1, and compared with available calculated and experimental data. Essential deviations between the new intensity measurements and calculated data accepted in HITRAN 2012 and GEISA 2015 forthcoming release are found.

Physical activity, sedentary behaviour, and socioeconomic status among Finnish girls and boys aged 6-8 years.

PubMed

Lampinen, Eeva-Kaarina; Eloranta, Aino-Maija; Haapala, Eero A; Lindi, Virpi; Väistö, Juuso; Lintu, Niina; Karjalainen, Panu; Kukkonen-Harjula, Katriina; Laaksonen, David; Lakka, Timo A

2017-05-01

We studied differences in physical activity (PA), sedentary behaviour (SB), and the types of PA and SB between Finnish girls and boys and children from different socioeconomic backgrounds (SES). We assessed PA, SB, parental education, and household income using detailed questionnaires in a representative population sample of 486 children (238 girls, 248 boys) aged 6-8 years. Girls spent on average 1.7 h/day and boys 2.0 h/day in total PA (p = 0.002). Altogether 66% of girls and 54% of boys had less than 2 h of total PA per day (p = 0.012). Girls had lower levels of unsupervised PA (45 vs. 54 min/day, p = 0.001), supervised PA (1.5 vs. 1.9 h/week, p = 0.009), and PA during school recess (1.8 vs. 1.9 h/week, p = 0.032) than boys. Girls had higher levels of total SB (3.8 vs. 3.4 h/day, p = 0.015) but lower levels of screen-based SB (1.5 vs. 1.9 h/day, p < 0.001) than boys. Lower parental education and household income were associated with lower levels of supervised PA in girls (p = 0.011 and p = 0.008, respectively) and in boys (p = 0.006 and p = 0.003, respectively). Lower parental education and household income were also related to higher levels of screen-based SB in boys (p = 0.005 and p < 0.001, respectively) but not in girls. Girls have lower levels of total, unsupervised, and supervised PA, PA during recess, and screen-based SB but higher levels of total SB than boys. Lower parental education and household income are associated with lower levels of supervised PA in both genders and higher levels of screen-based SB in boys.

Physical Activity is Associated with Higher Sleep Efficiency in the General Population: The CoLaus Study.

PubMed

Gubelmann, Cédric; Heinzer, Raphael; Haba-Rubio, José; Vollenweider, Peter; Marques-Vidal, Pedro

2018-03-30

To evaluate the association of objective physical activity (PA) and sedentary behaviour (SB) with sleep duration and quality. Cross-sectional study including 2649 adults (53.5% women, 45-86 years) from the general population. Proportions of time spent in PA and SB were measured using 14-day accelerometry. Low PA and high SB status were defined as the lowest and highest tertile of each behaviour. 'Inactive', 'Weekend warrior' and 'Regularly active' weekly patterns were also defined. Sleep parameters were derived from the accelerometer and validated questionnaires. High PA, relative to low PA, was associated with higher sleep efficiency [76.6 vs. 73.8%, p<0.01] and lower likelihood of evening chronotype [relative-risk ratio (RR) and 95%CI: 0.71 (0.52; 0.97)]. Similar associations were found for low SB relative to high SB. 'Weekend warriors', relative to 'Inactives', had higher sleep efficiency [76.4 vs. 73.9%, p<0.01] and lower likelihood of evening chronotype [RR: 0.63 (0.43; 0.93)]. 'Regularly actives', relative to 'Inactives', had higher sleep efficiency [76.7 vs. 73.9%, p<0.01] and tended to have less frequently an evening chronotype [RR: 0.75 (0.54; 1.04), p=0.09]. No associations were found for PA and SB with sleep duration, daytime sleepiness, insomnia, and risk of sleep apnea (after adjustment for body mass index). High PA and low SB individuals, even if they do not sleep longer, have higher sleep efficiency and have less frequently an evening chronotype.

Applying 1D Sediment Models to Reservoir Flushing Studies: Measuring, Monitoring, and Modeling the Spencer Dam Sediment Flush with HEC-RAS

DTIC Science & Technology

2016-07-01

approximately 5 hours (hr) after opening main gates. Multiple channels eroded (Figure 5), moving sediment through the dam throughout the first day...additional sediment evacuation was observed over the next 4 weeks. ERDC/CHL CHETN-XIV-52 July 2016 5 Figure 5. Multiple channels eroded...2015. A physically-based channel - modeling framework integrating HEC-RAS sediment transport capabilities and the USDA-ARS Bank-Stability and Toe-Erosion

MBE System for Antimonide Based Semiconductor Lasers

DTIC Science & Technology

1999-01-31

selectivity are reported as a function of plasma chemistry and DC self-bias. Experiment The samples used in this study are undoped bulk GaSb, InSb...Phys. Lett. 64(13), 1673-1675 (1994). 8. J. W. Lee, J. Hong, E. S. Lambers, C. R. Abernathy, S. J. Pearton, W. S. Hobson, and F. Ren, Plasma Chemistry and...AlGaAsSb are reported as functions of plasma chemistry , ICP power, RF self-bias, and chamber pressure. It is found that physical sputtering desorption of

The Structural, Photocatalytic Property Characterization and Enhanced Photocatalytic Activities of Novel Photocatalysts Bi2GaSbO7 and Bi2InSbO7 during Visible Light Irradiation

PubMed Central

Luan, Jingfei; Shen, Yue; Li, Yanyan; Paz, Yaron

2016-01-01

In order to develop original and efficient visible light response photocatalysts for degrading organic pollutants in wastewater, new photocatalysts Bi2GaSbO7 and Bi2InSbO7 were firstly synthesized by a solid-state reaction method and their chemical, physical and structural properties were characterized. Bi2GaSbO7 and Bi2InSbO7 were crystallized with a pyrochlore-type structure and the lattice parameter of Bi2GaSbO7 or Bi2InSbO7 was 10.356497 Å or 10.666031 Å. The band gap of Bi2GaSbO7 or Bi2InSbO7 was estimated to be 2.59 eV or 2.54 eV. Compared with nitrogen doped TiO2, Bi2GaSbO7 and Bi2InSbO7, both showed excellent photocatalytic activities for degrading methylene blue during visible light irradiation due to their narrower band gaps and higher crystallization perfection. Bi2GaSbO7 showed higher catalytic activity compared with Bi2InSbO7. The photocatalytic degradation of methylene blue followed by the first-order reaction kinetics and the first-order rate constant was 0.01470 min−1, 0.00967 min−1 or 0.00259 min−1 with Bi2GaSbO7, Bi2InSbO7 or nitrogen doped TiO2 as a catalyst. The evolution of CO2 and the removal of total organic carbon were successfully measured and these results indicated continuous mineralization of methylene blue during the photocatalytic process. The possible degradation scheme and pathway of methylene blue was also analyzed. Bi2GaSbO7 and Bi2InSbO7 photocatalysts both had great potential to purify textile industry wastewater. PMID:28773922

Mutations that abolish the ability of Ha-Ras to associate with Raf-1.

PubMed

Shirouzu, M; Koide, H; Fujita-Yoshigaki, J; Oshio, H; Toyama, Y; Yamasaki, K; Fuhrman, S A; Villafranca, E; Kaziro, Y; Yokoyama, S

1994-08-01

Recent studies have revealed that Ras can associate physically with Raf. In the present study, we tested 34 mutants of Ha-Ras carrying substitution(s) in the region of residues 23-71 for their ability to associate with Raf-1. Mouse Ba/F3 cell lysates were incubated with each mutant Ras protein, in either the guanosine 5'-[gamma-thio]triphosphate (GTP gamma S)- or the guanosine 5'-[beta-thio]diphosphate (GDP beta S)-bound form, and the anti-Ras antibody Y13-238. The immunoprecipitates were analysed for the presence of Raf-1 by Western blotting with an anti-Raf-1 antibody. Six mutants of Ras, E31K, P34G, T35S, D38N, D57A and A59T, failed to bind Raf-1. Mutations N26G, V29A, S39A, Y40W, R41A, V44A, V45E, L56A and T58A partially reduced the ability to bind Raf-1. All the other mutants could associate with Raf-1 with nearly the same efficiency as that of wild-type Ras. Thus, the Raf-I-binding ability of Ras appears to be affected by mutations in the N-terminal region, and in particular, by those in and neighboring the effector region (residues 32-40) and in the region (residues 56-59) flanking the N-terminal of Switch II. The abilities to bind Raf-1 and to induce neurite outgrowth of pheochromocytoma (PC) 12 cells correlate to each other for 22 Ras mutants. However, mutation A59T, which does not reduce the neurite-inducing or transforming activities, abolishes the ability to bind Raf-1. In contrast, mutations Y32F, K42A and L53A, which impair the neurite-inducing activity of Ras, have no effect on the Ras.Raf-1 association. Partially reduced Raf-1-binding ability was observed for mutants V29A, S39A, Y40W, R41A, V44A, L56A and T58A, which exhibit full neurite-inducing activity, and also for mutant V45E, which has no activity of neurite induction.

Patterns of physical activity, sedentary behavior, and diet in U.S. adolescents.

PubMed

Iannotti, Ronald J; Wang, Jing

2013-08-01

To identify patterns in adolescents' obesogenic behaviors and their relations to physical and psychological health. A nationally representative sample of 9,174 U.S. adolescents ages 11 to 16 years was surveyed on physical activity (PA), screen-based sedentary behavior (SB), frequency of consumption of healthy and unhealthy food items, weight status, weight control behavior, depression, physical symptoms, body dissatisfaction, overall health, and life satisfaction. Latent class analysis was used to identify patterns of PA, SB, and diet. A model with three latent classes best fit the data: Class 1 with high PA and high fruit and vegetable intake and low SB and intake of sweets, soft drinks, chips, and fries; Class 2 with high SB and high intake of sweets, soft drinks, chips, and fries; and Class 3 with low PA, low fruit and vegetable intake, and low intake of sweets, chips, and fries. Membership in the three classes was related to age, gender, race/ethnicity, and socioeconomic status. In addition, members of Class 1 (26.5%) were more likely to be of normal weight status and to fare well on most of the other health indices; of Class 2 (26.4%) were less likely to be trying to lose weight but scored poorly on the mental health indices; and of Class 3 (47.2%) were less likely to be underweight and reported greater body dissatisfaction. Three prevalent patterns of adolescent obesogenic behaviors were identified and these patterns related to weight status, depression, and other indicators of physical and psychological health. Published by Elsevier Inc.

Black holes: theory and observations (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 23 December 2015)

NASA Astrophysics Data System (ADS)

2016-07-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS), "Black holes: theory and observations," was held in the conference hall of the Lebedev Physical Institute, RAS, on 23 December 2015. The papers collected in this issue were written based on talks given at the session: (1) I D Novikov (Lebedev Physical Institute, Russian Academy of Sciences, Astro Space Center, Moscow; The Niels Bohr International Academy, The Niels Bohr Institute, Copenhagen; National Research Center 'Kurchatov Institute', Moscow) "Black holes, wormholes, and time machines"; (2) A M Cherepashchuk (Lomonosov Moscow State University, Sternberg Astronomical Institute, Moscow) "Observing stellar-mass and supermassive black holes"; (3) N S Kardashev (Lebedev Physical Institute, Russian Academy of Sciences, Astro Space Center, Moscow) "Millimetron space project: a tool for researching black holes and wormholes." Papers written on the basis of oral presentations 1, 2 are published below. • Observing stellar mass and supermassive black holes, A M Cherepashchuk Physics-Uspekhi, 2016, Volume 59, Number 7, Pages 702-712 • Black holes, wormholes, and time machines, I D Novikov Physics-Uspekhi, 2016, Volume 59, Number 7, Pages 713-715

Objectively Measured Sedentary Behavior, Obesity, and Psychological Well-Being: A Cross-Sectional Study of Japanese Schoolchildren.

PubMed

Ishii, Kaori; Shibata, Ai; Adachi, Minoru; Mano, Yoshiyuki; Oka, Koichiro

2017-04-01

Sedentary behaviors (SB) are associated with health indicators; however, there are currently very few studies that have examined these associations, especially in conjunction with psychological factors, in children. The current study examined the independent relationship between objectively assessed SB, and indicators of obesity and psychological well-being, among Japanese children. A total of 967 elementary-school children completed a cross-sectional survey. SB was measured with accelerometers for 7 consecutive days. Psychological well-being data (eg, anxiety and behavior problems) were collected via a self-report questionnaire. To determine the relationship of SB with degree of obesity and psychological well-being, linear regression analyses were conducted to relate the indicators of obesity and psychological well-being on SB, adjusted by gender, grade, percentage of moderate-to-vigorous physical activity per day, duration spent wearing the accelerometer, and degree of obesity. SB was significantly related to behavioral/emotional problems (β = .280, P = .010, R 2 = .015). There was a statistically significant relationship between SB and anxiety (β = .206, P = .059, R 2 = .007). No significant association with degree of obesity was found. Excess SB relates higher levels of behavioral/emotional problems and anxiety. These results can inspire the development of interventions that promote well-being and enhance psychological health, by focusing on SB in Japanese children.

Processing of the Liquid Xenon calorimeter's signals for timing measurements

NASA Astrophysics Data System (ADS)

Epshteyn, L. B.; Yudin, Yu V.

2014-09-01

One of the goals of the Cryogenic Magnetic Detector at Budker Institute of Nuclear Physics SB RAS (Novosibirsk, Russia) is a study of nucleons production in electron-positron collisions near threshold. The neutron-antineutron pair production events can be detected only by the calorimeters. In the barrel calorimeter the antineutron annihilation typically occurs by 5 ns or later after beams crossing. For identification of such events it is necessary to measure the time of flight of particles to the LXe-calorimeter with accuracy of about 3 ns. The LXe-calorimeter consists of 14 layers of ionization chambers with anode and cathode readout. The duration of charge collection to the anodes is about 4.5 mks, while the required accuracy of measuring of the signal arrival time is less than 1/1000 of that. Besides, the signals' shapes differ substantially from event to event, so the signal arrival time is measured in two stages. At the first stage, the signal arrival time is determined with an accuracy of 1-2 discretization periods, and initial values of parameters for subsequent fitting procedure are calculated. At the second stage, the signal arrival time is determined with the required accuracy by means of fitting of the signal waveform with a template waveform. To implement that, a special electronics has been developed which performs waveform digitization and On-Line measurement of signals' arrival times and amplitudes.

Development of a software for control of the Lidar complex at the IAO SB RAS small Lidar station

NASA Astrophysics Data System (ADS)

Marichev, V. N.; Bochkovskii, D. A.

2015-11-01

The problems are discussed in the wide circles of the scientific community in the end of the last and in the beginning of present century, related with climate change on both global and local scale. The complicated question of changing climatic and ecological systems under the effect of natural and anthropogenic factors requires the development and creation of atmospheric aerosol thermodynamic and spatial-temporal models, development of network of both ground-based and space-based services for monitoring of the atmosphere on a global scale [1, 2]. Measures on collection of great amount of data lead to the need of development of not only technical side of the solution to the problem, but also methodological, algorithmic and software. The last decade is marked by the widespread introduction of computer technology into science and increase of its consumer features, such as speed, volume of RAM and cash memory, as well as the ability of high-quality displaying the data. Therefore, the final item in the development of automation of the experiment and application of mathematical methods is the development of the software tools. Software should carry the main load in the processing and simulation of an experiment, and to be a link between theoreticians, developers of the processing methods and models of physical processes and experimentalists

Geoinformation web-system for processing and visualization of large archives of geo-referenced data

NASA Astrophysics Data System (ADS)

Gordov, E. P.; Okladnikov, I. G.; Titov, A. G.; Shulgina, T. M.

2010-12-01

Developed working model of information-computational system aimed at scientific research in area of climate change is presented. The system will allow processing and analysis of large archives of geophysical data obtained both from observations and modeling. Accumulated experience of developing information-computational web-systems providing computational processing and visualization of large archives of geo-referenced data was used during the implementation (Gordov et al, 2007; Okladnikov et al, 2008; Titov et al, 2009). Functional capabilities of the system comprise a set of procedures for mathematical and statistical analysis, processing and visualization of data. At present five archives of data are available for processing: 1st and 2nd editions of NCEP/NCAR Reanalysis, ECMWF ERA-40 Reanalysis, JMA/CRIEPI JRA-25 Reanalysis, and NOAA-CIRES XX Century Global Reanalysis Version I. To provide data processing functionality a computational modular kernel and class library providing data access for computational modules were developed. Currently a set of computational modules for climate change indices approved by WMO is available. Also a special module providing visualization of results and writing to Encapsulated Postscript, GeoTIFF and ESRI shape files was developed. As a technological basis for representation of cartographical information in Internet the GeoServer software conforming to OpenGIS standards is used. Integration of GIS-functionality with web-portal software to provide a basis for web-portal’s development as a part of geoinformation web-system is performed. Such geoinformation web-system is a next step in development of applied information-telecommunication systems offering to specialists from various scientific fields unique opportunities of performing reliable analysis of heterogeneous geophysical data using approved computational algorithms. It will allow a wide range of researchers to work with geophysical data without specific programming knowledge and to concentrate on solving their specific tasks. The system would be of special importance for education in climate change domain. This work is partially supported by RFBR grant #10-07-00547, SB RAS Basic Program Projects 4.31.1.5 and 4.31.2.7, SB RAS Integration Projects 4 and 9.

Using Web GIS "Climate" for Adaptation to Climate Change

NASA Astrophysics Data System (ADS)

Gordova, Yulia; Martynova, Yulia; Shulgina, Tamara

2015-04-01

A work is devoted to the application of an information-computational Web GIS "Climate" developed by joint team of the Institute of Monitoring of Climatic and Ecological Systems SB RAS and Tomsk State University to raise awareness about current and future climate change as a basis for further adaptation. Web-GIS "Climate» (http://climate.scert.ru/) based on modern concepts of Web 2.0 provides opportunities to study regional climate change and its consequences by providing access to climate and weather models, a large set of geophysical data and means of processing and visualization. Also, the system is used for the joint development of software applications by distributed research teams, research based on these applications and undergraduate and graduate students training. In addition, the system capabilities allow creating information resources to raise public awareness about climate change, its causes and consequences, which is a necessary step for the subsequent adaptation to these changes. Basic information course on climate change is placed in the public domain and is aimed at local population. Basic concepts and problems of modern climate change and its possible consequences are set out and illustrated in accessible language. Particular attention is paid to regional climate changes. In addition to the information part, the course also includes a selection of links to popular science network resources on current issues in Earth Sciences and a number of practical tasks to consolidate the material. These tasks are performed for a particular territory. Within the tasks users need to analyze the prepared within the "Climate" map layers and answer questions of direct interest to the public: "How did the minimum value of winter temperatures change in your area?", "What are the dynamics of maximum summer temperatures?", etc. Carrying out the analysis of the dynamics of climate change contributes to a better understanding of climate processes and further adaptation. Passing this course raises awareness of the general public, as well as prepares the user for subsequent registration in the system and work with its tools in conducting independent research. This work is partially supported by SB RAS project VIII.80.2.1, RFBR grants 13-05-12034 and 14-05-00502.

Physical activity and sedentary behavior in preschoolers: a longitudinal assessment of trajectories and determinants.

PubMed

Schmutz, Einat A; Haile, Sarah R; Leeger-Aschmann, Claudia S; Kakebeeke, Tanja H; Zysset, Annina E; Messerli-Bürgy, Nadine; Stülb, Kerstin; Arhab, Amar; Meyer, Andrea H; Munsch, Simone; Puder, Jardena J; Jenni, Oskar G; Kriemler, Susi

2018-04-04

Despite physical activity (PA) being recognized as a critically important factor for good physical and mental health already early in life and throughout the life course, prospective data on activity behavior during the preschool years remains scarce. This study examined trajectories and determinants of levels and change in total PA (TPA), moderate-to-vigorous PA (MVPA) and sedentary behavior (SB) in a representative sample of Swiss preschoolers. Data were drawn from the Swiss Preschoolers' Health Study (SPLASHY), a multi-site prospective cohort study including 555 children (53% boys) aged 2-to-6 years at baseline. A follow-up was conducted after 12 months. Activity behavior was measured using accelerometers. Information on 35 potential determinants from different socio-ecological domains was either directly measured or parent-reported. Trajectories of TPA, MVPA and SB over time were described for boys and girls. Linear mixed models were used to investigate factors that predicted levels and change in TPA, MVPA and SB. All children were sufficiently physically active according to published recommendations for preschoolers. Trajectory profiles revealed a marked increase in TPA and MVPA in boys and girls whereas SB remained fairly stable over time. Mixed modeling demonstrated that variables most relevant to determining PA levels were sex, age and activity temperament (all positively associated). Together with gross motor skills, birth weight, family structure (only for TPA) and season (only for MVPA), these factors accounted for 26 and 32% of total variance explained in TPA and MVPA, respectively. Activity temperament emerged as the strongest determinant of SB (negative association) and explained with sex, season and family structure 20% of total variance in SB. The presence of older siblings was the only factor that predicted change in PA over time. In this healthy physically active cohort of preschoolers, non-modifiable individual-level factors had the greatest influence on PA. The limited success of this and previous studies to identify modifiable determinants and the finding that most preschoolers were sufficiently active suggest that future attempts should provide insights into how preschoolers' activity levels can be maintained and fostered to prevent subsequent harmful declines attributable, amongst others, to educational transitions. Thus, good-quality longitudinal studies are needed. Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14).

Prevalence of sedentary behavior and its correlates among primary and secondary school students

PubMed Central

Ferreira, Rodrigo Wiltgen; Rombaldi, Airton José; Ricardo, Luiza Isnardi Cardoso; Hallal, Pedro Curi; Azevedo, Mario Renato

2016-01-01

Abstract Objective: To determine the students’ exposure to four different sedentary behavior (SB) indicators and their associations with gender, grade, age, economic status and physical activity level. Methods: A cross-sectional study was conducted in 2013. The SB was collected using the HELENA instrument, composed by screen time questions (TV, video games and internet) and sitting activities on school opposite shift. The cut point of ≥2h/day was used to categorize the outcome. The Poisson regression was used for associations between the outcome and the independent variables (95% significance level), controlling for confounding variables and the possible design effect. Results: The sample was composed by 8661 students. The overall prevalence of SB was 69.2% (CI95% 68.1–70.2) on weekdays, and 79.6% (CI95% 78.7–80.5) on weekends. Females were more associated with the outcome, except to electronic games. Advanced grades students were more involved in sitting tasks when compared to the early grades. Older students were more likely to surf on net for ≥2h/day. Higher economic level students were more likely to engage in video games and internet. Active individuals were less likely to engage in SB on weekdays. Conclusions: The prevalence of SB was high, mainly on weekends. The associations with sex, age, grade and physical activity level should be considered into elaboration of more efficient interventions on SB control. PMID:26826878

A study on the temperature dependence of the threshold switching characteristics of Ge2Sb2Te5

NASA Astrophysics Data System (ADS)

Lee, Suyoun; Jeong, Doo Seok; Jeong, Jeung-hyun; Zhe, Wu; Park, Young-Wook; Ahn, Hyung-Woo; Cheong, Byung-ki

2010-01-01

We investigated the temperature dependence of the threshold switching characteristics of a memory-type chalcogenide material, Ge2Sb2Te5. We found that the threshold voltage (Vth) decreased linearly with temperature, implying the existence of a critical conductivity of Ge2Sb2Te5 for its threshold switching. In addition, we investigated the effect of bias voltage and temperature on the delay time (tdel) of the threshold switching of Ge2Sb2Te5 and described the measured relationship by an analytic expression which we derived based on a physical model where thermally activated hopping is a dominant transport mechanism in the material.

Cognitive and Motivational Factors Associated with Sedentary Behavior: A Systematic Review

PubMed Central

Rollo, Scott; Gaston, Anca; Prapavessis, Harry

2016-01-01

Excessive time spent in sedentary behavior (SB) is associated with numerous health risks. These associations remain even after controlling for moderate-to-vigorous physical activity (PA) and body mass index, indicating that efforts to promote leisure time physical activity alone are insufficient. Cognitive and motivation variables represent potentially modifiable factors and have the potential of furthering our understanding of sedentary behavior. Hence, a systematic review was conducted to synthesize and critique the literature on the relationship between cognitive and motivational factors and sedentary behaviors. In April 2016, four electronic databases (Psych info, Pub Med, SPORTDiscus, Web of Science) were searched and a total of 4866 titles and abstracts were reviewed. After meeting inclusion criteria, study characteristics were extracted and the methodological quality of each study was assessed according to the Downs and Black Checklist. PRISMA guidelines for reporting of systematic reviews were followed. Twenty-five studies (16 cross-sectional, 8 longitudinal and one examining two populations and employing both a cross-sectional and prospective design) assessed 23 different cognitive and motivational factors. Seventeen studies were theory-based and 8 did not employ a theoretical model. Results showed that among SB-related cognitions, risk factors for greater sedentary time included having a more positive attitude towards SB, perceiving greater social support/norms for SB, reporting greater SB habits, having greater intentions to be sedentary, and having higher intrinsic, introjected, and external motivation towards SB. Protective factors associated with lower sedentary time included having greater feelings of self-efficacy/control over SB and greater intentions to reduce SB. Among PA-related cognitions, protective factors for lower SB included a more positive attitude towards PA, having greater social support/norms for PA, greater self-efficacy/control for PA, higher PA intentions, and higher intrinsic and identified motivation towards PA. In addition, feeling more supported and empowered in general was related with lower levels of SB. The average methodological quality score for included studies was 69% (SD = 9.15%; range 35–80%). In conclusion, a number of cognitive and motivational factors were identified that were associated with sedentarism. These findings have come from reasonably high quality studies. To further extend our understanding of the relation between cognitive and motivational factors and SB, more longitudinal, theory-driven studies examining cognitions and motivation from a sedentary perspective are required. PMID:29546206

10-year cumulative and bidirectional associations of domain-specific physical activity and sedentary behaviour with health-related quality of life in French adults: Results from the SU.VI.MAX studies.

PubMed

Omorou, Abdou Y; Vuillemin, Anne; Menai, Medhi; Latarche, Clotilde; Kesse-Guyot, Emmanuelle; Galan, Pilar; Hercberg, Serge; Oppert, Jean-Michel; Briançon, Serge

2016-07-01

The directionality of the associations of domain-specific physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) in adults remain insufficiently known. This study investigated the longitudinal associations of 10-year cumulative levels of PA and SB with HRQoL and the reverse associations. A sample of 2093 (47.8% men) participants from a cohort of French adult (SU.VI.MAX) was included. Data were collected at 3 time points (1998, 2001 and 2007) using the Modifiable Activity Questionnaire (MAQ) for PA (leisure-time and occupational) and SB (screen-viewing, reading and total sitting time) and the DUKE Health Profile for HRQoL. The cumulative level (from 0 to 3) referred to the number of time points where a high PA level, high SB or good HRQoL was reported. Regression models examined the 10-year cumulative level of PA, SB as predictors of HRQoL and reverse associations. The 10-year cumulative level of high PA, both leisure-time and occupational, predicted a higher HRQoL while the 10-year cumulative level of high screen-viewing time and high total sitting time was associated with lower HRQoL. For the reverse association, cumulative level of good HRQoL predicted more leisure-time PA, less screen-viewing time and less total sitting time but was not related to occupational PA. Relationships between PA, SB and HRQoL are complex and should not be oversimplified in one or the other direction. Taking into account domain-specific PA and SB in health promotion programs appears of prime importance to design interventions aiming at improving HRQoL. Copyright © 2016 Elsevier Inc. All rights reserved.

Physical Activity and Pediatric Obesity: A Quantile Regression Analysis

PubMed Central

Mitchell, Jonathan A.; Dowda, Marsha; Pate, Russell R.; Kordas, Katarzyna; Froberg, Karsten; Sardinha, Luís B.; Kolle, Elin; Page, Angela

2016-01-01

Purpose We aimed to determine if moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) were independently associated with body mass index (BMI) and waist circumference (WC) in children and adolescents. Methods Data from the International Children’s Accelerometry Database (ICAD) were used to address our objectives (N=11,115; 6-18y; 51% female). We calculated age and gender specific body mass index (BMI) and waist circumference (WC) Z-scores and used accelerometry to estimate MVPA and total SB. Self-reported television viewing was used as a measure of leisure time SB. Quantile regression was used to analyze the data. Results MVPA and total SB were associated with lower and higher BMI and WC Z-scores, respectively. These associations were strongest at the higher percentiles of the Z-score distributions. After including MVPA and total SB in the same model the MVPA associations remained, but the SB associations were no longer present. For example, each additional hour per day of MVPA was not associated with BMI Z-score at the 10th percentile (b=-0.02, P=0.170), but was associated with lower BMI Z-score at the 50th (b=-0.19, P<0.001) and 90th percentiles (b=-0.41, P<0.001). More television viewing was associated with higher BMI and WC and the associations were strongest at the higher percentiles of the Z-score distributions, with adjustment for MVPA and total SB. Conclusions Our observation of stronger associations at the higher percentiles indicate that increasing MVPA and decreasing television viewing at the population-level could shift the upper tails of the BMI and WC frequency distributions to lower values, thereby lowering the number of children and adolescents classified as obese. PMID:27755284

Microphysics of Clouds with the Relaxed Arakawa-Schubert Scheme (McRAS). Part I: Design and Evaluation with GATE Phase III Data.

NASA Astrophysics Data System (ADS)

Sud, Y. C.; Walker, G. K.

1999-09-01

A prognostic cloud scheme named McRAS (Microphysics of Clouds with Relaxed Arakawa-Schubert Scheme) has been designed and developed with the aim of improving moist processes, microphysics of clouds, and cloud-radiation interactions in GCMs. McRAS distinguishes three types of clouds: convective, stratiform, and boundary layer. The convective clouds transform and merge into stratiform clouds on an hourly timescale, while the boundary layer clouds merge into the stratiform clouds instantly. The cloud condensate converts into precipitation following the autoconversion equations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, as well as diffuse both horizontally and vertically with a fully interactive cloud microphysics throughout the life cycle of the cloud, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry.An evaluation of McRAS in a single-column model (SCM) with the Global Atmospheric Research Program Atlantic Tropical Experiment (GATE) Phase III data has shown that, together with the rest of the model physics, McRAS can simulate the observed temperature, humidity, and precipitation without discernible systematic errors. The time history and time mean in-cloud water and ice distribution, fractional cloudiness, cloud optical thickness, origin of precipitation in the convective anvils and towers, and the convective updraft and downdraft velocities and mass fluxes all simulate a realistic behavior. Some of these diagnostics are not verifiable with data on hand. These SCM sensitivity tests show that (i) without clouds the simulated GATE-SCM atmosphere is cooler than observed; (ii) the model's convective scheme, RAS, is an important subparameterization of McRAS; and (iii) advection of cloud water substance is helpful in simulating better cloud distribution and cloud-radiation interaction. An evaluation of the performance of McRAS in the Goddard Earth Observing System II GCM is given in a companion paper (Part II).

Clean Intermittent Catheterization in the School Setting

ERIC Educational Resources Information Center

Katrancha, Elizabeth D.

2008-01-01

Spina bifida (SB) is a neural tube defect that causes many physical and mental disabilities. Bowel and bladder incontinence is the disability seen most often in these students that requires the school nurse's attention. Clean intermittent catheterization (CIC) provides the student with SB a vehicle to reach a satisfactory level of continence,…

Ba-filled Ni–Sb–Sn based skutterudites with anomalously high lattice thermal conductivity

DOE PAGES

Paschinger, W.; Rogl, Gerda; Grytsiv, A.; ...

2016-06-21

Here, in this study, novel filled skutterudites Ba yNi 4Sb 12-xSn x (y max = 0.93) have been prepared by arc melting followed by annealing at 250, 350 and 450°C up to 30 days in vacuum-sealed quartz vials. Extension of the homogeneity region, solidus temperatures and structural investigations were performed for the skutterudite phase in the ternary Ni–Sn–Sb and in the quaternary Ba–Ni–Sb–Sn systems. Phase equilibria in the Ni–Sn–Sb system at 450°C were established by means of Electron Probe Microanalysis (EPMA) and X-ray Powder Diffraction (XPD). With rather small cages Ni 4(Sb,Sn) 12, the Ba–Ni–Sn–Sb skutterudite system is perfectly suitedmore » to study the influence of filler atoms on the phonon thermal conductivity. Single-phase samples with the composition Ni 4Sb 8.2Sn 3.8, Ba 0.42Ni 4Sb 8.2Sn 3.8 and Ba 0.92Ni 4Sb 6.7Sn 5.3 were used to measure their physical properties, i.e. temperature dependent electrical resistivity, Seebeck coefficient and thermal conductivity. The resistivity data demonstrate a crossover from metallic to semiconducting behaviour. The corresponding gap width was extracted from the maxima in the Seebeck coefficient data as a function of temperature. Single crystal X-ray structure analyses at 100, 200 and 300 K revealed the thermal expansion coefficients as well as Einstein and Debye temperatures for Ba 0.73Ni 4Sb 8.1Sn 3.9 and Ba 0.95Ni 4Sb 6.1Sn 5.9. These data were in accordance with the Debye temperatures obtained from the specific heat (4.4 K < T < 140 K) and Mössbauer spectroscopy (10 K < T < 290 K). Rather small atom displacement parameters for the Ba filler atoms indicate a severe reduction in the “rattling behaviour” consistent with the high levels of lattice thermal conductivity. The elastic moduli, collected from Resonant Ultrasonic Spectroscopy ranged from 100 GPa for Ni 4Sb 8.2Sn 3.8 to 116 GPa for Ba 0.92Ni 4Sb 6.7Sn 5.3. The thermal expansion coefficients were 11.8 × 10 -6 K -1 for Ni 4Sb 8.2Sn 3.8 and 13.8 × 10 -6 K -1 for Ba 0.92Ni 4Sb 6.7Sn 5.3. The room temperature Vickers hardness values vary within the range from 2.6 GPa to 4.7 GPa. Lastly, severe plastic deformation via high-pressure torsion was used to introduce nanostructuring; however, the physical properties before and after HPT showed no significant effect on the materials thermoelectric behaviour.« less

Studies of Nano-structured Se77Sb23- x Ge x Thin Films Prepared by Physical Vapor Condensation Technique

NASA Astrophysics Data System (ADS)

Alvi, M. A.

2017-02-01

Bulk Se77Sb23- x Ge x material with x = 4 and 12 was prepared by employing a melt quench technique. Its amorphous as well as glassy nature was confirmed by x-ray diffraction analysis and nonisothermal differential scanning calorimetry measurements. The physical vapor condensation technique was applied to prepare nanostructured thin films of Se77Sb23- x Ge x material. The surface morphology of the films was examined using field-emission scanning electron microscopy, revealing average particle size between 20 nm and 50 nm. Systematic investigation of optical absorption data indicated that the optical transition was indirect in nature. The dark conductivity (dc conductivity) of nano-structured Se77Sb23- x Ge x thin films was also investigated at temperatures from 313 K to 463 K, revealing that it tended to increase with increasing temperature. Analyses of our experimental data also indicate that the conduction is due to thermally supported tunneling of charge carriers in confined states close to the band edges. The calculated values of activation energy agree well with the optical bandgap.

Comparison of Summer and Winter Objectively Measured Physical Activity and Sedentary Behavior in Older Adults: Age, Gene/Environment Susceptibility Reykjavik Study.

PubMed

Arnardottir, Nanna Yr; Oskarsdottir, Nina Dora; Brychta, Robert J; Koster, Annemarie; van Domelen, Dane R; Caserotti, Paolo; Eiriksdottir, Gudny; Sverrisdottir, Johanna E; Johannsson, Erlingur; Launer, Lenore J; Gudnason, Vilmundur; Harris, Tamara B; Chen, Kong Y; Sveinsson, Thorarinn

2017-10-21

In Iceland, there is a large variation in daylight between summer and winter. The aim of the study was to identify how this large variation influences physical activity (PA) and sedentary behavior (SB). Free living PA was measured by a waist-worn accelerometer for one week during waking hours in 138 community-dwelling older adults (61.1% women, 80.3 ± 4.9 years) during summer and winter months. In general, SB occupied about 75% of the registered wear-time and was highly correlated with age (β = 0.36). Although the differences were small, more time was spent during the summer in all PA categories, except for the moderate-to-vigorous PA (MVPA), and SB was reduced. More lifestyle PA (LSPA) was accumulated in ≥5-min bouts during summer than winter, especially among highly active participants. This information could be important for policy makers and health professionals working with older adults. Accounting for seasonal difference is necessary in analyzing SB and PA data.

Post-hospitalization course and predictive signs of suicidal behavior of suicidal patients admitted to a psychiatric hospital: a 2-year prospective follow-up study.

PubMed

Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Utsumi, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Harima, Hirohiko; Tatebayashi, Yoshitaka; Kumagai, Naoki; Nozu, Makoto; Ishii, Hidetoki; Okazaki, Yuji

2012-10-31

Suicidal patients admitted to a psychiatric hospital are considered to be at risk of suicidal behavior (SB) and suicide. The present study aimed to seek predictors of SB recurrence of the high-risk patients by examining their post-hospitalization course. The design was 2-year prospective follow-up study of patients consecutively admitted with SB to a psychiatric center in Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined in structured interviews. Subsequently, the subjects underwent a series of follow-up assessments at 6-month intervals. The assessment included inquiries into SB recurrence, its accompanying suicidal intent (SI) and SF-8 health survey. Analyses of serial change over time in the follow-up data and Cox proportional hazards regression analyses of SB recurrence were performed. 106 patients participated in this study. The dropout rate during the follow-up was 9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6% (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and maltreatment in the developmental period were predictive of SB as a whole, and younger age and hopelessness prior to index admission were predictive of suicide attempt. Regarding diagnostic variables, anxiety disorders and personality disorders appeared to have predictive value for SB. Additionally, poor physical health assessed during the follow-up was indicated as a possible short-term predictor of SB recurrence. This study demonstrated a high incidence of SB and suicide and possible predictors of SB recurrence in the post-hospitalization period of psychiatric suicidal patients. Specialized interventions should be developed to reduce the suicide risk of this patient population.

GaSb solar cells grown on GaAs via interfacial misfit arrays for use in the III-Sb multi-junction cell

NASA Astrophysics Data System (ADS)

Nelson, George T.; Juang, Bor-Chau; Slocum, Michael A.; Bittner, Zachary S.; Laghumavarapu, Ramesh B.; Huffaker, Diana L.; Hubbard, Seth M.

2017-12-01

Growth of GaSb with low threading dislocation density directly on GaAs may be possible with the strategic strain relaxation of interfacial misfit arrays. This creates an opportunity for a multi-junction solar cell with access to a wide range of well-developed direct bandgap materials. Multi-junction cells with a single layer of GaSb/GaAs interfacial misfit arrays could achieve higher efficiency than state-of-the-art inverted metamorphic multi-junction cells while forgoing the need for costly compositionally graded buffer layers. To develop this technology, GaSb single junction cells were grown via molecular beam epitaxy on both GaSb and GaAs substrates to compare homoepitaxial and heteroepitaxial GaSb device results. The GaSb-on-GaSb cell had an AM1.5g efficiency of 5.5% and a 44-sun AM1.5d efficiency of 8.9%. The GaSb-on-GaAs cell was 1.0% efficient under AM1.5g and 4.5% at 44 suns. The lower performance of the heteroepitaxial cell was due to low minority carrier Shockley-Read-Hall lifetimes and bulk shunting caused by defects related to the mismatched growth. A physics-based device simulator was used to create an inverted triple-junction GaInP/GaAs/GaSb model. The model predicted that, with current GaSb-on-GaAs material quality, the not-current-matched, proof-of-concept cell would provide 0.5% absolute efficiency gain over a tandem GaInP/GaAs cell at 1 sun and 2.5% gain at 44 suns, indicating that the effectiveness of the GaSb junction was a function of concentration.

Is the time right for quantitative public health guidelines on sitting? A narrative review of sedentary behaviour research paradigms and findings.

PubMed

Stamatakis, Emmanuel; Ekelund, Ulf; Ding, Ding; Hamer, Mark; Bauman, Adrian E; Lee, I-Min

2018-06-10

Sedentary behaviour (SB) has been proposed as an 'independent' risk factor for chronic disease risk, attracting much research and media attention. Many countries have included generic, non-quantitative reductions in SB in their public health guidelines and calls for quantitative SB targets are increasing. The aim of this narrative review is to critically evaluate key evidence areas relating to the development of guidance on sitting for adults. We carried out a non-systematic narrative evidence synthesis across seven key areas: (1) definition of SB, (2) independence of sitting from physical activity, (3) use of television viewing as a proxy of sitting, (4) interpretation of SB evidence, (5) evidence on 'sedentary breaks', (6) evidence on objectively measured sedentary SB and mortality and (7) dose response of sitting and mortality/cardiovascular disease. Despite research progress, we still know little about the independent detrimental health effects of sitting, and the possibility that sitting is mostly the inverse of physical activity remains. Unresolved issues include an unclear definition, inconsistencies between mechanistic and epidemiological studies, over-reliance on surrogate outcomes, a very weak epidemiological evidence base to support the inclusion of 'sedentary breaks' in guidelines, reliance on self-reported sitting measures, and misinterpretation of data whereby methodologically inconsistent associations are claimed to be strong evidence. In conclusion, public health guidance requires a consistent evidence base but this is lacking for SB. The development of quantitative SB guidance, using an underdeveloped evidence base, is premature; any further recommendations for sedentary behaviour require development of the evidence base and refinement of the research paradigms used in the field. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Longitudinal Physical Activity, Body Composition, and Physical Fitness in Preschoolers.

PubMed

Leppänen, Marja H; Henriksson, Pontus; Delisle Nyström, Christine; Henriksson, Hanna; Ortega, Francisco B; Pomeroy, Jeremy; Ruiz, Jonatan R; Cadenas-Sanchez, Cristina; Löf, Marie

2017-10-01

This study aimed to investigate longitudinal associations of objectively measured physical activity (PA) and sedentary behavior (SB) with body composition and physical fitness at a 12-month follow-up in healthy Swedish 4-yr-old children. The data from the population-based MINISTOP trial were collected between 2014 and 2016, and this study included the 138 children who were in the control group. PA and SB were assessed using the wrist-worn ActiGraph (wGT3x-BT) accelerometer during seven 24-h periods and, subsequently, defined as SB, light-intensity PA, moderate-intensity PA, vigorous-intensity PA (VPA), and moderate-to-vigorous PA (MVPA). Body composition was measured using air-displacement plethysmography and physical fitness (cardiorespiratory fitness, lower and upper muscular strength as well as motor fitness) by the PREFIT fitness battery. Linear regression and isotemporal substitution models were applied. Greater VPA and MVPA at the age of 4.5 yr were associated with higher fat-free mass index (FFMI) at 5.5 yr (P < 0.001 and P = 0.044, respectively). Furthermore, greater VPA and MVPA at the age of 4.5 yr were associated with higher scores for cardiorespiratory fitness, lower body muscular strength, and motor fitness at 12-month follow-up (P = 0.001 to P = 0.031). Substituting 5 min·d of SB, light-intensity PA, or moderate-intensity PA for VPA at the age of 4.5 yr were associated with higher FFMI, and with greater upper and lower muscular strength at 12-month follow-up (P < 0.001 to P = 0.046). Higher VPA and MVPA at the age of 4.5 yr were significantly associated with higher FFMI and better physical fitness at 12-month follow-up. Our results indicate that promoting high-intensity PA at young ages may have long-term beneficial effects on childhood body composition and physical fitness, in particular muscular strength.

Validity and responsiveness of the Global Physical Activity Questionnaire (GPAQ) in assessing physical activity during pregnancy

PubMed Central

Micklesfield, Lisa K.; van Poppel, Mireille N. M.; Norris, Shane A.; Sattler, Matteo C.; Dietz, Pavel

2017-01-01

The physiological and biomechanical changes that occur during pregnancy make accurate measurement of physical activity (PA) a challenge during this unique period. The Global Physical Activity Questionnaire (GPAQ) has been used extensively in low-to-middle income countries, but has never been validated in a pregnant population. In this longitudinal study, 95 pregnant women (mean age: 29.5±5.7 years; BMI: 26.9±5.0 kg/m2) completed the GPAQ and were asked to wear an accelerometer for 7 days at two time points during pregnancy (14–18 and 29–33 weeks gestation). There was a significant difference between accelerometry and GPAQ when measuring moderate-to-vigorous physical activity (MVPA) at 29–33 weeks gestation (16.6 vs 21.4 min/day; p = 0.02) as well as sedentary behaviour (SB) at both 14–18 weeks (457.0 vs 300 min/day; p < 0.01) and 29–33 weeks gestation (431.5 vs 300 min/day; p < 0.01). There was poor agreement between the GPAQ and accelerometry for both PA and SB at both time points (ICC: -0.05–0.08). Bland Altman plots indicated that the GPAQ overestimates PA by 14.8 min/day at 14–18 weeks and by 15.8 min/day at 29–33 weeks gestation. It underestimates SB by 127.5 min/day at 14–18 weeks and by 89.2 min/day at 29–33 weeks gestation. When compared to accelerometry, the GPAQ shows poor agreement and appears to overestimate PA and underestimate SB during pregnancy. PMID:28552977

[Risk Factors Associated With School Bullying in Local Authority Schools in Four Municipalities of Valle del Cauca, Colombia. Year 2009].

PubMed

Hernández Carrillo, Mauricio; Gutiérrez Martínez, María Isabel

2013-09-01

To determine the association between family and social relationships and School Bullying (SB) among peers in public education institutions in four municipalities of the department of Valle del Cauca, Colombia, during 2009. A case-control study matched by sex and educational institution was carried out. The study population came from a secondary database provided by the Departof Health Secretaryhealth, which consisted of data gathered in a survey of schoolchildren enrolled in grades 6 to 11. The CISNEROS scale and the Family APGAR test were applied to measure outcome and exposure variables. A conditional logistic regression model was obtained to explain SB. It was found that schoolchildren living with a family where verbal and physical violence prevails, as well as in a hostile neighborhood, are more vulnerable to SB. The probability of being an SB victim is explained by: family dysfunction (OR=2.67; 95%CI, 1.05-6.82), verbal aggression at home (OR=2.81; 95%CI, 1.45-5.46), physical punishing parents (OR=2.53; 95%CI, 1.12-5.75), and neighbors who are physically aggressive to each other (OR=1.87; 95% CI, 1.00-3.56). The study confirmed that reported by Lopez, who suggested that victimization and school rejection in adolescence is related to factors outside the classroom, such as the quality of communication between parents and children. As regards family influence in the SB, Bowes indicates that a positive family atmosphere is significantly associated with the resilience of school victimization. Furthermore, being physically punished by parents generates low self-esteem in the schoolchild that leads to lack of self-protective attitudes to the attacks that occur within the school. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.

PubMed

Arnardottir, Nanna Yr; Koster, Annemarie; Domelen, Dane R Van; Brychta, Robert J; Caserotti, Paolo; Eiriksdottir, Gudny; Sverrisdottir, Johanna E; Sigurdsson, Sigurdur; Johannsson, Erlingur; Chen, Kong Y; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Sveinsson, Thorarinn

2016-01-01

Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n=352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days. More GM (β=0.11; p=0.044) and WM (β=0.11; p=0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (β=0.14; p=0.0037) and WM (β=0.11; p=0.030) was associated with TPA. The 5-year change in WM was associated with SB (β=-0.11; p=0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions. Copyright © 2015 Elsevier B.V. All rights reserved.

Use of global positioning system for physical activity research in youth: ESPAÇOS Adolescentes, Brazil.

PubMed

Alberico, Claudia Oliveira; Schipperijn, Jasper; Reis, Rodrigo S

2017-10-01

The built environment is an important factor associated with physical activity and sedentary behavior (SB) during adolescence. This study presents the methods for objective assessment of context-specific moderate to vigorous physical activity (MVPA) and SB, as well as describes results from the first project using such methodology in adolescents from a developing country. An initial sample of 381 adolescents was recruited from 32 census tracts in Curitiba, Brazil (2013); 80 had their homes geocoded and wore accelerometer and GPS devices for seven days. Four domains were defined as important contexts: home, school, transport and leisure. The majority of participants (n=80) were boys (46; 57.5%), with a normal BMI (52; 65.0%) and a mean age (SD) of 14.5 (5.5) years. Adolescents spent most of their time at home, engaging in SB. Overall, the largest proportion of MVPA was while in transport (17.1% of time spent in this context) and SB while in leisure (188.6min per day). Participants engaged in MVPA for a median of 28.7 (IQR 18.2-43.2) and 17.9 (IQR 9.2-32.1) minutes during week and weekend days, respectively. Participants spent most of their day in the leisure and home domains. The use of Geographic Information System (GIS), Global Positioning System (GPS) and accelerometer data allowed objective identification of the amount of time spent in MVPA and SB in four different domains. Though the combination of objective measures is still an emerging methodology, this is a promising and feasible approach to understanding interactions between people and their environments in developing countries. Copyright © 2017 Elsevier Inc. All rights reserved.

Android Adiposity and Lack of Moderate and Vigorous Physical Activity Are Associated With Insulin Resistance and Diabetes in Aging Adults.

PubMed

Peterson, Mark D; Al Snih, Soham; Serra-Rexach, José A; Burant, Charles

2015-08-01

Physical inactivity and excess adiposity are thought to be interdependent "lifestyle" factors and thus, many older adults are at exaggerated risk for preventable diseases. The purposes of this study were to determine the degree of discordance between body mass index (BMI) and adiposity among adults older than 50 years, and to determine the extent to which direct measures of adiposity, and objectively measured sedentary behavior (SB) and physical activity (PA) are associated with insulin resistance (IR) or diabetes. A population representative sample of 2,816 individuals, aged 50-85 years, was included from the combined 2003-2006 National Health and Nutrition Examination Survey (NHANES) datasets. BMI, percent body fat (%BF) and android adiposity as determined by dual energy x-ray absorptiometry, objectively measured SB and PA, established markers of cardiometabolic risk, IR, and type 2 diabetes were analyzed. Approximately 50% of the men and 64% of the women who were normal weight according to BMI had excessive %BF. Adults with the least SB and greatest moderate and vigorous PA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest activity had highest risk. Greater android adiposity stores were robustly associated with IR or diabetes in all adults, independent of SB and activity. Among men, less moderate-to-vigorous PA was associated with IR or diabetes; whereas among women, less lifestyle moderate activity was associated with IR or diabetes. Android adiposity and low moderate and vigorous PA are the strongest predictors of IR or diabetes among aging adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Growth and characterization of AlInAsSb layers lattice-matched to GaSb

NASA Astrophysics Data System (ADS)

Tournet, J.; Rouillard, Y.; Tournié, E.

2017-11-01

We report on the growth by solid-source MBE of random-alloy AlxIn1-xAsySb1-y layers lattice-matched to (0 0 1)-GaSb substrates, with xAl ∈ [0.25; 0.75]. The samples quality and morphology were characterized by X-ray diffraction, Nomarski microscopy and atomic force microscopy. Layers grown at 400 °C demonstrated smooth surfaces and no sign of phase decomposition. Samples with xAl ≤ 0.60 demonstrated photoluminescence (PL) at 300 K whereas samples with higher Al content only demonstrated PL at low temperature. Samples grown at 430 °C, in contrast, exhibited PL at low temperature only, whatever their composition. Inferred bandgap energies corroborate the estimation of a non-null quaternary bowing parameter made by Donati, Kaspi and Malloy in Journal of Applied Physics 94 (2003) 5814. Upon annealing, the PL peak energies increased, getting even closer to the theoretical values. These results are in agreement with recently published results on digital AlInAsSb alloys. Our work, which reports the first evidence for PL emission from random-alloy AlInAsSb layers lattice-matched to GaSb, opens the way to their use in optoelectronic devices.

Associations between objectively-measured sedentary behaviour and physical activity with bone mineral density in adults and older adults, the NHANES study.

PubMed

Chastin, S F M; Mandrichenko, O; Helbostadt, J L; Skelton, D A

2014-07-01

Lack of physical activity (PA) is an important modifiable risk factor for bone mineral density (BMD). Time spent in sedentary behaviour (SB), or time spent in non-exercising seated and reclining postures, has recently emerged as a new public health risk, independent of the amount of time someone spends being active. As national surveys report that adults spend on average 8h per day being sedentary, rising to 10h a day in older age, it has been hypothesised that a repeated exposure to sitting in modern daily life, whether it is for travelling, working or leisure, might have a deleterious effect on bone health in a way that mirrors the results of studies into the effect of lengthy periods of bed-rest. The aim of this study was to investigate for the first time a) how time spent in SB is associated with bone mineral density (BMD), b) whether this association changes depending on the amount of time spent engaging in different intensity levels of PA, and c) if the pattern of accumulation of SB and long uninterrupted periods of SB are associated with BMD. The 2005/2006 National Health and Nutrition Examination Survey (NHANES), is a cross-sectional study of a representative sample of the US population that is conducted biannually by the National Centers for Disease Control. PA and SB were assessed objectively over 7 days using an Actigraph accelerometer and BMD was measured via dual-energy X-ray absorptiometry. In this study, data are presented on four regions of the femur (femoral neck, trochanter, inter trochanter and total femur) and total spine (L1-L4). The associations between BMD, SB and PA levels were examined using multiple linear regressions stratified by gender. In addition, the association between the pattern of accumulation of SB (quantified as frequency and duration of SB) and BMD was also investigated. All models were adjusted for known risk factors associated with BMD. In total, data for 2117 individuals, aged 23-90+years (males N=1158), were available to analyse SB and femur BMD and 1942 individuals (males N=1053) for analysis of SB and spine BMD. There was no evidence of an association between SB time and hip or spinal BMD in men. For men, time spent doing moderate to vigorous activity (MVPA) and vigorous activity (VIG) was associated with higher total femur and the other hip sub-region BMD. The regression coefficient was BMVPA=0.306 (95% CI: 0.021-0.591)g/cm2 for each 10 minute increment in daily MVPA. For VIG, the regression coefficient is BVIG=0.320 (95% CI: 0.058-0.583) but this cannot be interpreted linearly as time spent in vigorous activity was square root transformed. In women, SB was negatively associated with total femur BMD and all sub-regions but not MVPA nor VIG. The regression coefficient for total femur BMD was BSB = -0.159 (95% CI: -0.241-0.076)g/cm2 for each 10 minute increment spent being sedentary each day. In addition, the duration of SB bouts was deleteriously associated with BMD for the total femur and of other hip sub-regions, but the number of bouts of SB did not have a significant effect. These associations were found to be independent of the amount of MVPA and VIG that women engage in. No associations were found between SB or PA and spinal BMD for either men or women. These results provide the first evidence that repeated exposure to sitting (SB), measured objectively in daily life, is deleteriously associated with BMD of the total femur and of all hip sub-regions in women, independent of the amount of time women engage in moderate and vigorous activity. This suggests that SB might be a risk factor for bone health in women independent of whether they engage in physical activity. In addition, the duration of SB bouts, rather than their frequency, appears to be deleteriously associated with BMD of the total femur and of all hip sub-regions. Future research should investigate the effect on bone health of interventions which set out to reduce SB and the duration of SB bouts in comparison, and as adjunct, to the promotion of PA. For men, SB is not significantly associated with BMD of the femur or spine and the results appear to confirm that moderate and vigorous activity has a protective effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Bile acids modulate signaling by functional perturbation of plasma membrane domains.

PubMed

Zhou, Yong; Maxwell, Kelsey N; Sezgin, Erdinc; Lu, Maryia; Liang, Hong; Hancock, John F; Dial, Elizabeth J; Lichtenberger, Lenard M; Levental, Ilya

2013-12-13

Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

Seasonal variation in physical activity, sedentary behaviour and sleep in a sample of UK adults.

PubMed

O'Connell, Sophie E; Griffiths, Paula L; Clemes, Stacy A

2014-01-01

Physical activity (PA), sedentary behaviour (SB), sleep and diet have all been associated with increased risk for chronic disease. Seasonality is often overlooked as a determinant of these behaviours in adults. Currently, no study has simultaneously monitored these behaviours in UK adults to assess seasonal variation. The present study investigated whether PA, SB, sleep and diet differed over season in UK adults. Forty-six adults (72% female; age = 41.7 ± 14.4 years, BMI = 24.9 ± 4.4 kg/m(2)) completed four 7-day monitoring periods; one during each season of the year. The ActiGraph GT1M was used to monitor PA and SB. Daily sleep diaries monitored time spent in bed (TIB) and total sleep time (TST). The European Prospective Investigation of Cancer (EPIC) food frequency questionnaire (FFQ) assessed diet. Repeated measures ANOVAs were used to identify seasonal differences in behaviours. Light-intensity PA was significantly higher in summer and spring (p < 0.001). SB and TIB were significantly higher in winter (p < 0.01). There were no seasonal variations detected in moderate-vigorous PA, TST or diet (p > 0.05). Findings support the concept that health promotion campaigns need to encourage year-round participation in light intensity PA, whilst limiting SB, particularly during the winter months.

Classroom-Based Physical Activity and Sedentary Behavior Interventions in Adolescents: A Systematic Review and Meta-Analysis.

PubMed

McMichan, Lauren; Gibson, Ann-Marie; Rowe, David A

2018-05-01

It is reported that 81% of adolescents are insufficiently active. Schools play a pivotal role in promoting physical activity (PA) and reducing sedentary behavior (SB). The aim of this systematic review and meta-analysis was to evaluate classroom-based PA and SB interventions in adolescents. A search strategy was developed using the Population Intervention Comparison Outcome Study (PICOS) design framework. Articles were screened using strict inclusion criteria. Study quality was assessed using the Effective Public Health Practice Project quality assessment tool ( http://www.ephpp.ca/tools.html ). Outcome data for preintervention and postintervention were extracted, and effect sizes were calculated using Cohen's d. The strategy yielded 7574 potentially relevant articles. Nine studies were included for review. Study quality was rated as strong for 1 study, moderate for 5 studies, and weak for 3 studies. Five studies were included for meta-analyses, which suggested that the classroom-based interventions had a nonsignificant effect on PA (P = .55, d = 0.05) and a small, nonsignificant effect on SB (P = .16, d = -0.11). Only 9 relevant studies were found, and the effectiveness of the classroom-based PA and SB interventions varied. Based on limited empirical studies, there is not enough evidence to determine the most effective classroom-based methodology to increase PA and SB.

Environmental and personal correlates of physical activity and sedentary behavior in African American women: An ecological momentary assessment study.

PubMed

Zenk, Shannon N; Horoi, Irina; Jones, Kelly K; Finnegan, Lorna; Corte, Colleen; Riley, Barth; Wilbur, JoEllen

2017-04-01

The authors of this study examined within-person associations of environmental factors (weather, built and social environmental barriers) and personal factors (daily hassles, affect) with moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) in African American women aged 25-64 years living in metropolitan Chicago (n = 97). In 2012-13, for seven days, women wore an accelerometer and were signaled five times per day to complete a survey covering environmental and personal factors on a study-provided smartphone. Day-level measures of each were derived, and mixed regression models were used to test associations. Poor weather was associated with a 27.3% reduction in daily MVPA. Associations between built and social environmental barriers and daily MVPA or SB were generally not statistically significant. Negative affect at the first daily signal was associated with a 38.6% decrease in subsequent daily MVPA and a 33.2-minute increase in subsequent daily SB. Each one-minute increase in MVPA during the day was associated with a 2.2% higher likelihood of positive affect at the end of the day. SB during the day was associated with lower subsequent positive affect. Real-time interventions that address overcoming poor weather and negative affect may help African American women increase MVPA and/or decrease SB.

Understanding children's sedentary behaviour: a qualitative study of the family home environment.

PubMed

Granich, Joanna; Rosenberg, Michael; Knuiman, Matthew; Timperio, Anna

2010-04-01

Electronic media (EM) (television, electronic games and computer) use has been associated with overweight and obesity among children. Little is known about the time spent in sedentary behaviour (SB) among children within the family context. The aim of this study was to explore how the family home environment may influence children's electronic-based SB. Focus groups and family interviews were conducted with 11- to 12-year old children (n = 54) and their parents (n = 38) using a semi-structured discussion guide. Transcripts were analysed using a thematic content approach. A brief self-completed questionnaire was also used to measure leisure behaviour and electronic devices at home. Children incorporated both sedentary and physical activities into their weekly routine. Factors influencing children's EM use included parent and sibling modelling and reinforcement, personal cognitions, the physical home environment and household EM use rules and restrictions. Participants were not concerned about the excessive time children spent with EM. This under-recognition emerged as a personal influencing factor and was viewed as a major barrier to modifying children's electronic-based SB. Efforts to reduce SB in children should focus on the influencing factors that reciprocally interact within the family home. An emphasis on increasing awareness about the risks associated with spending excessive time in screen-based activities should be a priority when developing intervention strategies aimed at modifying the time children spend in SB.

Family satisfaction, pain, and quality-of-life in emerging adults with spina bifida: a longitudinal analysis.

PubMed

Bellin, Melissa H; Dicianno, Brad E; Osteen, Philip; Dosa, Nienke; Aparicio, Elizabeth; Braun, Patricia; Zabel, T Andrew

2013-08-01

This study uses the Life Course Model for Spina Bifida (SB) to advance knowledge of factors associated with change in quality-of-life (QOL) among emerging adults with SB. Forty-eight participants (mean [SD], 22.04 [2.16] yrs) completed self-report questionnaires at two time points, 15 mos apart. Four QOL domains (physical health, psychological, social relationships, and environment) were measured using the World Health Organization QOL-BREF version. SB clinical data were collected via chart reviews. Paired t tests and reliable change indices evaluated group- and individual-level QOL change, respectively. Multiple regression analyses tested the contributions of the Life Course variables in explaining change in QOL over time. No significant group-level differences in the QOL domains were found between time 1 and time 2, but there was substantial individual variation in QOL over time. SB severity was related to a decline only in psychological QOL (B = -0.68, P = 0.02). Increased pain was associated with reduced physical health (B = -0.29, P = 0.049) and psychological (B = -0.29, P = 0.03) QOL at time 2, whereas greater family satisfaction was related to improved QOL in several domains. Clinicians should be aware of the negative impact of pain and the protective influence of family satisfaction on QOL in emerging adults with SB.

Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health.

PubMed

Fenton, Sally A M; Veldhuijzen van Zanten, Jet J C S; Duda, Joan L; Metsios, George S; Kitas, George D

2018-02-01

RA is a chronic autoimmune disease characterized by high grade-inflammation, and associated with elevated cardiovascular risk, rheumatoid-cachexia and functional impairment. Sedentary behaviour (SB) is linked to heightened inflammation, and is highly pervasive in RA, likely as a result of compromised physical function and persistent fatigue. This high sedentarity may exacerbate the inflammatory process in RA, and hold relevance for disease-related outcomes. The aim of this narrative review is to provide an overview of the definition, measurement and health relevance of SB in the context of RA. Contradictions are highlighted with regard to the manner in which SB is operationalized, and the significance of SB for disease outcomes in RA is outlined. The advantages and disadvantages of SB measurement approaches are also discussed. Against this background, we summarize studies that have reported SB and its health correlates in RA, and propose directions for future research. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ras proteins have multiple functions in vegetative cells of Dictyostelium.

PubMed

Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

2010-11-01

During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

PREFACE: International Congress on Energy Fluxes and Radiation Effects (EFRE-2014)

NASA Astrophysics Data System (ADS)

2014-11-01

The International Congress on Energy Fluxes and Radiation Effects 2014 (EFRE 2014) was held in Tomsk, Russia, on September 21-26, 2014. The organizers of the Congress were the Institute of High Current Electronics SB RAS and Tomsk Polytechnic University. EFRE 2014 combines three international conferences which are regularly held in Tomsk, Russia: the 18th International Symposium on High-Current Electronics (18th SHCE), the 12th International Conference on Modification of Materials with Particle Beams and Plasma Flows (12th CMM) and the 16th International Conference on Radiation Physics and Chemistry of Condensed Matter (16th RPC). The International Conference on Radiation Physics and Chemistry of Condensed Matter is a traditional representative forum devoted to the discussion of the fundamental problems of physical and chemical non-linear processes in condensed matter (mainly inorganic dielectrics) under the action of particle and photon beams of all types including pulsed power laser radiation. The International Symposium on High-Current Electronics is held biannually in Tomsk, Russia. The program of the conferences covers a wide range of scientific and technical areas including pulsed power technology, ion and electron beams, high-power microwaves, plasma and particle beam sources, modification of materials, and pulsed power applications in chemistry, biology and medicine. The 12th International Conference on Modification of Materials with Particle Beams and Plasma Flows is devoted to the discussion of the fundamental and applied issues in the field of modification of materials properties with particle beams and plasma flows. The six-day Congress brought together more than 250 specialists and scientists from different countries and organizations and provided an excellent opportunity to exchange knowledge, make oral contributions and poster presentations, and initiate discussion on the topics of interest. The proceedings were edited by Victor Lisitsyn, Vladimir Lopatin, and Anna Bogdan. We appreciate the contribution of the invited speakers and all participants, as well as sponsors "Intech Analytics" and "MICROSPLAV" for making the Congress successful.

Shc and the mechanotransduction of cellular anchorage and metastasis.

PubMed

Terada, Lance S

2017-02-17

Tissue cells continually monitor anchorage conditions by gauging the physical properties of their underlying matrix and surrounding environment. The Rho and Ras GTPases are essential components of these mechanosensory pathways. These molecular switches control both cytoskeletal as well as cell fate responses to anchorage conditions and are thus critical to our understanding of how cells respond to their physical environment and, by extension, how malignant cells gainsay these regulatory pathways. Recent studies indicate that 2 proteins produced by the SHC1 gene, thought for the most part to functionally oppose each other, collaborate in their ability to respond to mechanical force by initiating respective Rho and Ras signals. In this review, we focus on the coupling of Shc and GTPases in the cellular response to mechanical anchorage signals, with emphasis on its relevance for cancer.

Post-hospitalization course and predictive signs of suicidal behavior of suicidal patients admitted to a psychiatric hospital: a 2-year prospective follow-up study

PubMed Central

2012-01-01

Background Suicidal patients admitted to a psychiatric hospital are considered to be at risk of suicidal behavior (SB) and suicide. The present study aimed to seek predictors of SB recurrence of the high-risk patients by examining their post-hospitalization course. Method The design was 2-year prospective follow-up study of patients consecutively admitted with SB to a psychiatric center in Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined in structured interviews. Subsequently, the subjects underwent a series of follow-up assessments at 6-month intervals. The assessment included inquiries into SB recurrence, its accompanying suicidal intent (SI) and SF-8 health survey. Analyses of serial change over time in the follow-up data and Cox proportional hazards regression analyses of SB recurrence were performed. Results 106 patients participated in this study. The dropout rate during the follow-up was 9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6% (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and maltreatment in the developmental period were predictive of SB as a whole, and younger age and hopelessness prior to index admission were predictive of suicide attempt. Regarding diagnostic variables, anxiety disorders and personality disorders appeared to have predictive value for SB. Additionally, poor physical health assessed during the follow-up was indicated as a possible short-term predictor of SB recurrence. Conclusions This study demonstrated a high incidence of SB and suicide and possible predictors of SB recurrence in the post-hospitalization period of psychiatric suicidal patients. Specialized interventions should be developed to reduce the suicide risk of this patient population. PMID:23114285

Performance of Ge-Sb-Bi-Te-B Recording Media for Phase-Change Optical Disks

NASA Astrophysics Data System (ADS)

Lee, Chain-Ming; Yen, Wen-Shin; Liu, Ren-Haur; Chin, Tsung-Shune

2001-09-01

We investigated the physical properties of GeSbBiTeB materials and examined the feasibility for phase change recording. The studied compositions were Ge4Sb0.5Bi0.5Te5 and Ge2Sb1.5Bi0.5Te5 with B doping. The coexistence of Bi and B atoms into both Ge4SbTe5 and Ge2Sb2Te5 lattice maintains single fcc structure without phase separation. The Bi substitution shows benefits in decreasing crystallization temperature and activation energy, however the reflectivity is slightly reduced. 3 With small amount addition of boron about 1 at.%, the reflectivity can be increased. 2 Conventional 4-layer structure of digital versatile disk-random access memory (DVD-RAM) 2.6 GB format was used to prepare the disks for dynamic characterization and overwrite cyclability evaluations. The disk with Ge4Sb0.5Bi0.5Te5(B) recording layer shows large noise fluctuation and low overwrite erase ratio, suggesting that the crystallization speed is still insufficient. While the disk with Ge2Sb1.5Bi0.5Te5(B) recording layer shows lower writing and erasing powers, stable noise level and high overwrite erase ratio, indicating the capability for DVD-RAM applications. The effect of B doping was verified to enhance the signal amplitude and modulation.

Physical activity and sedentary behavior in people with major depressive disorder: A systematic review and meta-analysis.

PubMed

Schuch, Felipe; Vancampfort, Davy; Firth, Joseph; Rosenbaum, Simon; Ward, Philip; Reichert, Thaís; Bagatini, Natália Carvalho; Bgeginski, Roberta; Stubbs, Brendon

2017-03-01

Low levels of physical activity (PA) and sedentary behavior (SB) are independent risk factors for cardiovascular disease and premature mortality in people with major depressive disorder (MDD). Investigate levels of PA and SB and their predictors in people with MDD. Electronic databases were searched from inception till 04/2016 for articles measuring PA and SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with MDD. Random-effects meta-analyses and meta-regression analyses were conducted. Twenty-four eligible studies were identified including 2901 people with MDD (78.4% female, mean age=54 years; range: 21-77 years). People with MDD spent 126.0min (95%CI=91.9-160.1) per day engaging in all types of PA and spent 8.5hours (95%CI=7.51-9.62) during their waking day being sedentary. Compared to controls, people with MDD spent less time in total PA (SMD=-0.25, 95%CI=-0.03 to 0.15) and moderate to vigorous PA (SMD=-0.30, 95%CI=-0.40 to 0.21) and engaged in higher levels of SB (SMD=0.09, 95%CI=0.01-0.18). The proportion of people with MDD not meeting the recommended PA guidelines was 67.8% (n=13 studies), which was higher in studies relying on objective versus self-report measures (85.7% v 62.1%, p=0.04). People with MDD were more likely than controls to not meeting the recommended PA guidelines (OR = 1.50, 95%CI = 1.10–2.10). Heterogeneity was evident in most analyses. Adults with MDD engage in low levels of PA and high levels of SB. PA and SB are independent predictors of mortality, therefore, future lifestyle interventions targeting both the prevention of SB and adoption and maintenance of PA are warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

Operant Conditioning: A Tool for Special Physical Educators in the 1980s.

ERIC Educational Resources Information Center

Dunn, John M.; French, Ron

1982-01-01

The usefulness of operant conditioning for the special physical educator in managing behavior problems is pointed out, and steps to follow in applying operant conditioning techniques are outlined. (SB)

Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

PubMed

Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R

2015-08-01

The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.

Changes in microstructure and physical properties of skutterudites after severe plastic deformation.

PubMed

Rogl, Gerda; Grytsiv, Andriy; Bursik, Jiri; Horky, Jelena; Anbalagan, Ramakrishnan; Bauer, Ernst; Mallik, Ramesh Chandra; Rogl, Peter; Zehetbauer, Michael

2015-02-07

The best p-type skutterudites with ZT > 1.1 so far are didymium (DD) filled, Fe/Co substituted, Sb-based skutterudites. DD0.68Fe3CoSb12 was prepared using an annealing-reacting-melting-quenching technique followed by ball milling and hot pressing. After severe plastic deformation via high-pressure torsion (HPT), no phase changes but particular structural variations were achieved, leading to modified transport properties with higher ZT values. Although after measurement-induced heating some of the HPT induced defects were annealed out, a still attractive ZT-value was preserved. In this paper we focus on explanations for these changes via TEM investigations, Raman spectroscopy and texture measurements. The grain sizes and dislocation densities, evaluated from TEM images, showed that (i) the majority of cracks generated during high-pressure torsion are healed during annealing, leaving only small pores, that (ii) the grains have grown, and that (iii) the dislocation density is decreased. While Raman spectra indicate that after HPT processing and annealing the vibration modes related to the shorter Sb-Sb bonds in the Sb4 rings are more affected than those related to the longer Sb-Sb bonds, almost no visible changes were observed in the pole intensity and/or orientation.

Superconductivity in iron-based compounds (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 29 January 2014)

NASA Astrophysics Data System (ADS)

2014-08-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS), entitled 'Superconductivity in iron-based compounds', was held on 29 January 2014 at the conference hall of the Lebedev Physical Institute, RAS. The agenda of the session, announced on the website http://www.gpad.ac.ru of the RAS Physical Sciences Division listed the following reports: (1) Eremin I M (Institut für Theoretische Physik III, Ruhr-Universität Bochum, Bochum, Deutschland; Kazan (Volga region) Federal University, Kazan, Russian Federation) "Antiferromagnetism in iron-based superconductors: interaction of the magnetic, orbital, and lattice degrees of freedom"; (2) Korshunov M M (Kirenskii Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk) "Superconducting state in iron-based materials and spin-fluctuation pairing theory"; (3) Kuzmicheva T E (Lebedev Physical Institute, Russian Academy of Sciences, Moscow; Lomonosov Moscow State University) "Andreev spectroscopy of iron-based superconductors: temperature dependence of the order parameters and scaling of Δ_L, S with T_C"; (4) Eltsev Yu F (Lebedev Physical Institute, Russian Academy of Sciences, Moscow) "Synthesis and study of the magnetic and transport properties of iron-based superconductors of the 122 family". Papers written on the basis of oral presentations 1-4 are published below. • Antiferromagnetism in iron-based superconductors: magnetic order in the model of delocalized electrons, I M Eremin Physics-Uspekhi, 2014, Volume 57, Number 8, Pages 807-813 • Superconducting state in iron-based materials and spin-fluctuation pairing theory, M M Korshunov Physics-Uspekhi, 2014, Volume 57, Number 8, Pages 813-819 • Andreev spectroscopy of iron-based superconductors: temperature dependence of the order parameters and scaling of Δ_L, S with T_C, T E Kuzmicheva, S A Kuzmichev, M G Mikheev, Ya G Ponomarev, S N Tchesnokov, V M Pudalov, E P Khlybov, N D Zhigadlo Physics-Uspekhi, 2014, Volume 57, Number 8, Pages 819-827 • Magnetic and transport properties of single crystals of Fe-based superconductors of the 122 family, Yu F Eltsev, K S Pervakov, V A Vlasenko, S Yu Gavrilkin, E P Khlybov, V M Pudalov Physics-Uspekhi, 2014, Volume 57, Number 8, Pages 827-832

KIDS OUT! Protocol of a brief school-based intervention to promote physical activity and to reduce screen time in a sub-cohort of Finnish eighth graders.

PubMed

Jussila, Anne-Mari; Vasankari, Tommi; Paronen, Olavi; Sievänen, Harri; Tokola, Kari; Vähä-Ypyä, Henri; Broberg, Anna; Aittasalo, Minna

2015-07-10

Adolescents' physical activity (PA) is decreasing and sedentary behavior (SB) increasing alarmingly. Insufficient PA and excessive SB are both related to various health risks indicating that interventions to promote adolescents' PA and to reduce their SB are needed. Schools have a great potential to reach most adolescents, and in Finland health education (HE) as stand-alone subject provides an excellent platform for health promotion. This paper describes the protocol and evaluation (RE-AIM) of an intervention developed for three HE lessons to increase PA and reduce SB during leisure among 8(th) graders. All city-owned secondary schools in Tampere (n = 14) were invited to the study and were randomized in pairs to intervention (n = 7) and comparison group (n = 7). A specific content on PA and SB based on Health Action Process Approach model was integrated into routinely scheduled three HE lessons with the help of educational material: SoftGIS-questionnaire followed by feedback views on adolescents' current PA and SB, FeetEnergy-homework leaflet for adolescents, FeetEnergy-video in YouTube, FeetEnergy-poster for classroom and FeetEnergy-leaflet for parents. In the comparison group standard HE lessons were held. The primary indicators of Effectiveness are changes in PA and SB and in their psychosocial factors as well as in parental interference with PA and SB. The measurement points are baseline, 4 weeks after the intervention and 7 months from baseline, the last indicating also the measurement point for individual level Maintenance. The measures are accelerometers, 7-day activity diaries and questionnaires. The evaluation of Reach, Adoption and Implementation is based on the data collected during the intervention. Maintenance at organizational level is assessed two years after the intervention with a questionnaire to the HE teachers. The intervention was implemented in 2012 and the last measurements to assess organizational Maintenance were conducted in the end of 2014. A detailed description of the protocol and evaluation is provided to enable replication and better understanding of the findings, which will be reported in 2015. The findings will add our current knowledge about the feasibility and effectiveness of integrating simple structured elements into the HE lessons to increase PA and reduce SB in adolescents. NCT01633918 (June 27th, 2012).

Thermoelectric device including an alloy of GeTe and AgSbTe as the P-type element

DOEpatents

Skrabek, Emanuel Andrew; Trimmer, Donald Smith

1976-01-01

Improved alloys suitable for thermoelectric applications and having the general formula: (AgSbTe.sub.2).sub.1.sub.-x + (GeTe).sub.x wherein x has a value of about 0.80 and 0.85, have been found to possess unexpectedly high thermoelectric properties such as efficiency index, as well as other improved physical properties.

Lifestyle Practices and Obesity in Malaysian Adolescents

PubMed Central

Teo, Pey Sze; Nurul-Fadhilah, Abdullah; Aziz, Mohd Ezane; Hills, Andrew P.; Foo, Leng Huat

2014-01-01

Aim: To determine the influence of physical activity (PA) and sedentary behavior (SB) on obesity profiles of 454 Malaysian adolescents aged 12 to 19. Methods: Validated PA and SB questionnaires were used and body composition assessed using anthropometry and dual-energy X-ray absorptiometry (DXA). Results: Gender-specific multivariate analyses showed boys with high levels of total PA and moderate-to-vigorous physical activity (MVPA) exhibited significantly lower levels of total body fat, percent body fat and android fat mass compared with low PA and MVPA groups, after adjusting for potential confounders. Girls with high SB levels showed significantly higher BMI, waist circumference and DXA-derived body fat indices than those at lower SB level. Multiple logistic analyses indicated that boys with low levels of total PA and MVPA had significantly greater obesity risk, 3.0 (OR 3.0; 95% CI, 1.1–8.1; p < 0.05) and 3.8-fold (OR 3.8; 95% CI, 1.4–10.1; p < 0.01), respectively, than more active boys. Only in girls with high SB level was there a significantly increased risk of obesity, 2.9 times higher than girls at low SP levels (OR 2.8; 95% CI, 1.0–7.5; p < 0.05). Conclusions: The present findings indicate that higher PA duration and intensity reduced body fat and obesity risk while high screen-based sedentary behaviors significantly adversely influenced body fat mass, particularly amongst girls when the PA level was low. PMID:24886753

Lifestyle practices and obesity in Malaysian adolescents.

PubMed

Teo, Pey Sze; Nurul-Fadhilah, Abdullah; Aziz, Mohd Ezane; Hills, Andrew P; Foo, Leng Huat

2014-05-30

To determine the influence of physical activity (PA) and sedentary behavior (SB) on obesity profiles of 454 Malaysian adolescents aged 12 to 19. Validated PA and SB questionnaires were used and body composition assessed using anthropometry and dual-energy X-ray absorptiometry (DXA). Gender-specific multivariate analyses showed boys with high levels of total PA and moderate-to-vigorous physical activity (MVPA) exhibited significantly lower levels of total body fat, percent body fat and android fat mass compared with low PA and MVPA groups, after adjusting for potential confounders. Girls with high SB levels showed significantly higher BMI, waist circumference and DXA-derived body fat indices than those at lower SB level. Multiple logistic analyses indicated that boys with low levels of total PA and MVPA had significantly greater obesity risk, 3.0 (OR 3.0; 95% CI, 1.1-8.1; p < 0.05) and 3.8-fold (OR 3.8; 95% CI, 1.4-10.1; p < 0.01), respectively, than more active boys. Only in girls with high SB level was there a significantly increased risk of obesity, 2.9 times higher than girls at low SP levels (OR 2.8; 95% CI, 1.0-7.5; p < 0.05).   The present findings indicate that higher PA duration and intensity reduced body fat and obesity risk while high screen-based sedentary behaviors significantly adversely influenced body fat mass, particularly amongst girls when the PA level was low.

Examining Influences of Parenting Styles and Practices on Physical Activity and Sedentary Behaviors in Latino Children in the United States: Integrative Review

PubMed Central

Muñoz, Mario A; Wallington, Sherrie F; Greaney, Mary L

2018-01-01

Background Research indicates that parents influence their children’s physical activity (PA) and sedentary behaviors (SB) through their parenting styles and practices. Objective The objectives of this paper were to evaluate existing research examining the associations between parenting styles, parenting practices, and PA and SB among Latino children aged between 2 and 12 years, highlight limitations of the existing research, and generate suggestions for future research. Methods The method of this integrative review was informed by methods developed by Whittemore and Knafl, which allow for the inclusion of qualitative, quantitative, and mixed-methods studies. Using the Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines, five electronic academic databases (PubMed, SPORTDiscus, PsycINFO, PsycARTICLES, and CINAHL) were searched for peer-reviewed, full-text papers published in English. Of the 641 unique citations identified, 67 full-text papers were retrieved, and 16 were selected for review. Results The majority of the 16 reviewed studies were conducted with predominantly Mexican American or Mexican immigrant samples, and only 1 study examined the association between parenting styles and Latino children’s PA and SB. Most (n=15) reviewed studies assessed the influence of parenting practices on children’s PA and SB, and they provide good evidence that parenting practices such as offering verbal encouragement, prompting the child to be physically active, providing logistic support, engaging and being involved in PA, monitoring, and offering reinforcement and rewards encourage, facilitate, or increase children’s PA. The examined studies also provide evidence that parenting practices, such as setting rules and implementing PA restrictions due to safety concerns, weather, and using psychological control discourage, hinder, or decrease children’s PA. Conclusions Because this review found a very small number of studies examining the relationship between parenting styles and Latino children’s PA and SB, additional research is needed. Given that the majority of reviewed studies were conducted with predominantly Mexican American or Mexican immigrant samples, additional research examining parenting styles, parenting practices, and PA and SB among multiethnic Latino groups is needed to design interventions tailored to the needs of this ethnically diverse population group. PMID:29382629

Seismic structures beneath Popocatepetl (Mexico) and Gorely (Kamchatka) volcanoes derived from passive tomography studies

NASA Astrophysics Data System (ADS)

Kuznetsov, Pavel; Koulakov, Ivan

2014-05-01

A number of active volcanoes are observed in different parts of the world, and they attract great interest of scientists. Comparing their characteristics helps in understanding the origin and mechanisms of their activity. One of the most effective methods for studying the deep structure beneath volcanoes is passive source seismic tomography. In this study we present results of tomographic inversions for two active volcanoes located in different parts of the world: Popocatepetl (Mexico) and Gorely (Kamchatka, Russia). In the past century both volcanoes were actively erupted that explains great interest to their detailed investigations. In both cases we made the full data analysis starting from picking the arrival times from local events. In the case of the Popocatepetl study, a temporary seismological network was deployed by GFZ for the period from December 1999 to July 2000. Note that during this period there were a very few events recorded inside the volcano. Most of recorded earthquakes occurred in surrounding areas and they probably have the tectonic nature. We performed a special analysis to ground the efficiency of using these data for studying seismic structure beneath the network installed on the volcano. The tomographic inversion was performed using the LOTOS code by Koulakov (2009). Beneath the Popocatepetl volcano we have found a zone of strong anti-correlation between P- and S-velocities that leaded to high values of Vp/Vs ratio. Similar features were found for some other volcanoes in previous studies. We interpret these anomalies as zones of high content of fluids and melts that are related to active magma sources. For the case of Gorely volcano we used the data of a temporary network just deployed in summer 2013 by our team from IPGG, Novosibirsk. Luckily, during the field works, the volcano started to manifest strong seismic activity. In this period, 100 - 200 volcanic events occurred daily. We collected the continuous seismic records from 20 stations for 5-7 days that gives us the possibility to locate several hundreds of events and to build a preliminary seismic model beneath the Gorely volcano. We found a zone of low S-velocity located beneath the SE flank of the volcano, just between the Gorely and Mutnovsky volcanoes. This may serve as an argument for feeding these volcanoes from a single source. Although Popocatepetl and Gorely volcanoes are considerably different in their size and eruption characteristics, we found some similar features in the seismic structures, such as anti-correlation of P- and S- anomalies and high Vp/Vs ratio patterns below summits. This provides common patterns that give us the keys for understanding the general mechanism of working the volcanic systems. This study was partly supported by the projects #7.3 of BES RAS, IP SB RAS #20 and IP SB-FEB RAS #42

Magnetic and Ionospheric Observations in the Far Eastern Region of Russia During the Magnetic Storm of 5 April 2010

NASA Astrophysics Data System (ADS)

Baishev, D. G.; Moiseyev, A. V.; Boroyev, R. N.; Kobyakova, S. E.; Stepanov, A. E.; Mandrikova, O. V.; Solovev, I. S.; Khomutov, S. Yu.; Polozov, Yu. A.; Yoshikawa, A.; Yumoto, K.

2015-12-01

Magnetic and ionospheric disturbances in the far eastern region of Russia during the magnetic storm of 5 April 2010 are studied using data of geophysical stations operated by IKFIA SB RAS and IKIR FEB RAS. By performing wavelet analysis of experimental data, the wavelet powers of geomagnetic perturbations at different stations are estimated, in an attempt to investigate the dynamical development of a geomagnetic storm. It is shown that, though weak geomagnetic disturbances were present prior to the main phase of magnetic storm, the variations of the magnetic field during a storm development were found to be rather strong. The highest intensity of geomagnetic disturbances during the interplanetary shock at the Earth's magnetosphere was observed at KTN (L~9) while at ZYK (L~4) strongest geomagnetic perturbations occurred during the magnetospheric substorm with the onset at 09:03 UT. Large geomagnetic fluctuations were recorded at TIX and CHD (L~5-6), when the High-Intensity Long-Duration Continuous AE Activity (HILDCAA) was observed on 6 April 2010. Ionospheric conditions at YAK (L~3.4) and PET (L~2.2) were characterized by a pre-storm enhancement in the electron density in the F2 layer on 4 April 2010 and prolonged negative phase of the ionospheric storm during the main and recovery phases of magnetic storm on 6-8 April 2010. These experimental results underscore the importance of multi-instrumental observations and provide clues to the complex interactive processes.

Investigating the ionosphere response to exhaust products of ``Progress'' cargo spacecraft engines on the basis of Irkutsk Incoherent Scatter Radar data

NASA Astrophysics Data System (ADS)

Shpynev, Boris; Alsatkin, Sergei; Khakhinov, Vitaliy; Lebedev, Valentin

2017-04-01

The FSUE Central Research Institute of Machine Building (TsNIIMash), Rocket and Space Corporation "Energia", and Institute of Solar-Terrestrial Physics of Siberian Branch of Russian Academy of Sciences (ISTP SB RAS) jointly conducted the active space experiment "Radar-Progress" in 2007-2015. During this experiment, we used the Irkutsk Incoherent Scatter Radar to study space-time characteristics of ionospheric disturbances generated by exhaust products of "Progress" cargo spacecraft engines. As the basic effect during exhaust product injection, we consider the formation of new centers for recombination of ambient ionospheric ions O+ on molecules of water and carbon dioxide. This produces an ionization "hole" in the region of injection. In nighttime conditions when the majority of experiments were performed, this hole was filled by hydrogen ions from the plasmasphere, thus the ion composition in the vicinity of the hole and incoherent scatter spectra were changed. For successful observation of the ionization hole dynamics, the critical factors are the degree of radar antenna diagram filling by exhaust products and the velocity of the thermospheric neutral wind, which makes exhaust gases move from the antenna diagram. These two factors lead to the poor repeatability of successful experiments. Successful experiments recorded a decrease in electron density up to 35 % in the hole that existed for 30 min. The lifetime of the region with high concentration of H+ ions can be as long as one hour.

Chemical Substitution-Induced and Competitive Formation of 6H and 3C Perovskite Structures in Ba3-xSrxZnSb2O9: The Coexistence of Two Perovskites in 0.3 ≤ x ≤ 1.0.

PubMed

Li, Jing; Jiang, Pengfei; Gao, Wenliang; Cong, Rihong; Yang, Tao

2017-11-20

6H and 3C perovskites are important prototype structures in materials science. We systemically studied the structural evolution induced by the Sr 2+ -to-Ba 2+ substitution to the parent 6H perovskite Ba 3 ZnSb 2 O 9 . The 6H perovskite is only stable in the narrow range of x ≤ 0.2, which attributes to the impressibility of [Sb 2 O 9 ]. The preference of 90° Sb-O-Sb connection and the strong Sb 5+ -Sb 5+ electrostatic repulsion in [Sb 2 O 9 ] are competitive factors to stabilize or destabilize the 6H structure when chemical pressure was introduced by Sr 2+ incorporation. Therefore, in the following, a wide two-phase region containing 1:2 ordered 6H-Ba 2.8 Sr 0.2 ZnSb 2 O 9 and rock-salt ordered 3C-Ba 2 SrZnSb 2 O 9 was observed (0.3 ≤ x ≤ 1.0). In the final, the successive symmetry descending was established from cubic (Fm3̅m, 1.3 ≤ x ≤ 1.8) to tetragonal (I4/m, 2.0 ≤ x ≤ 2.4), and finally to monoclinic (I2/m, 2.6 ≤ x ≤ 3.0). Here we proved that the electronic configurations of B-site cations, with either empty, partially, or fully filled d-shell, would also affect the structure stabilization, through the orientation preference of the B-O covalent bonding. Our investigation gives a deeper understanding of the factors to the competitive formation of perovskite structures, facilitating the fine manipulation on their physical properties.

Large disparity between gallium and antimony self-diffusion in gallium antimonide.

PubMed

Bracht, H; Nicols, S P; Walukiewicz, W; Silveira, J P; Briones, F; Haller, E E

2000-11-02

The most fundamental mass transport process in solids is self-diffusion. The motion of host-lattice ('self-') atoms in solids is mediated by point defects such as vacancies or interstitial atoms, whose formation and migration enthalpies determine the kinetics of this thermally activated process. Self-diffusion studies also contribute to the understanding of the diffusion of impurities, and a quantitative understanding of self- and foreign-atom diffusion in semiconductors is central to the development of advanced electronic devices. In the past few years, self-diffusion studies have been performed successfully with isotopically controlled semiconductor heterostructures of germanium, silicon, gallium arsenide and gallium phosphide. Self-diffusion studies with isotopically controlled GaAs and GaP have been restricted to Ga self-diffusion, as only Ga has two stable isotopes, 69Ga and 71Ga. Here we report self-diffusion studies with an isotopically controlled multilayer structure of crystalline GaSb. Two stable isotopes exist for both Ga and Sb, allowing the simultaneous study of diffusion on both sublattices. Our experiments show that near the melting temperature, Ga diffuses more rapidly than Sb by over three orders of magnitude. This surprisingly large difference in atomic mobility requires a physical explanation going beyond standard diffusion models. Combining our data for Ga and Sb diffusion with related results for foreign-atom diffusion in GaSb (refs 8, 9), we conclude that the unusually slow Sb diffusion in GaSb is a consequence of reactions between defects on the Ga and Sb sublattices, which suppress the defects that are required for Sb diffusion.

Effect of Sb content on the physical properties of Ge-Se-Te chalcogenide glasses

NASA Astrophysics Data System (ADS)

Vashist, Priyanka; Anjali, Patial, Balbir Singh; Thakur, Nagesh

2018-05-01

In the present study, the bulk as-(Se80Te20)94-xGe6Sbx (x = 0, 1, 2, 4, 6, 8) glasses were synthesized using melt quenching technique. The physical properties viz coordination number, lone pair of electrons, number of constraints, glass transition temperature, mean bond energy, cohesive energy, electro-negativity and average heat of atomization of the investigated composition are reported and discussed. It is inferred that on increasing Sb content; average coordination number, average number of constraints, mean bond energy, cohesive energy and glass transition temperature increases but lone pair of electrons, average heat of atomization and deviation of stoichiometry decreases.

Fundamental motor skill, physical activity, and sedentary behavior in socioeconomically disadvantaged kindergarteners.

PubMed

Gu, Xiangli

2016-10-01

Guided by Stodden et al's conceptual model, the main purpose of the study was to examine the relation between fundamental motor skills (FMS; locomotor and objective control skills), different intensity levels of physical activity (light PA [LPA], moderate-to-vigorous PA [MVPA], and vigorous PA[VPA]), and sedentary behavior (SB) in socioeconomically disadvantaged kindergarteners. A prospective design was used in this study and the data were collected across the 2013-2014 academic school year. Participants were 256 (129 boys; 127 girls; Mage = 5.37, SD = 0.48) kindergarteners recruited from three public schools in the southern United States. Results found that FMS were significantly related to LPA, MVPA, VPA, and SB. Regression analyses indicate that locomotor skills explained significant variance for LPA (6.4%; p < .01), MVPA (7.9%; p < .001), and VPA (5.3%; p < .01) after controlling for weight status. Mediational analysis supports the significant indirect effect of MVPA on the relation between FMS and SB (95% CI: [-0.019, -0.006]). Adequate FMS development during early childhood may result in participating in more varied physical activities, thus leading to lower risk of obesity-related behaviors.

Prediction of bone mineral density and content from measures of physical activity and sedentary behavior in younger and older females.

PubMed

Braun, Saori I; Kim, Youngdeok; Jetton, Amy E; Kang, Minsoo; Morgan, Don W

2015-01-01

Little is known regarding the extent to which physical activity (PA) and sedentary behavior (SB) influence bone mineral content (BMC) and bone mineral density (BMD) in females across the lifespan. Data from 2232 females aged 12 years and older collected as part of the 2007-2008 National Health and Nutrition Examination Survey were analyzed. Categories of PA and SB were used to predict femoral and spinal BMD and BMC in four age groups (G1: 12-17; G2: 18-39; G3: 40-64; G4: ≥ 65 years). Self-reported PA categories included sufficient moderate-to-vigorous recreational PA (S-MVRPA) and insufficient MVRPA (I-MVRPA). G1 females who accumulated S-MVRPA displayed greater femoral and spinal BMC and BMD compared to G1 females who displayed I-MVRPA. For G4 females, higher levels of SB were associated with lower femoral BMC and BMD. These findings highlight the importance of engaging in sufficient moderate-to-vigorous physical activity during adolescence and reducing sedentary behavior in older adults to improve bone health in females.

On the first direct detection of gravitational waves (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 2 March 2016)

NASA Astrophysics Data System (ADS)

2016-09-01

A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS), "On the first direct detection of gravitational waves," was held in the conference hall of the Lebedev Physical Institute, RAS on 2 March 2016. The papers collected in this issue were written based on talks given at the session: (1) Pustovoit V I (Scientific and Technological Center of Unique Instrumentation, Moscow) "On the direct detection of gravitational waves"; (2) Braginsky V B, Bilenko I A, Vyatchanin S P, Gorodetsky M L, Mitrofanov V P, Prokhorov L G, Strigin S E, Khalili F Ya (Lomonosov Moscow State University, Moscow) "The road to the discovery of gravitational waves"; (3) Khazanov E A (Institute of Applied Physics, RAS, Nizhny Novgorod) "Thermooptics of magnetoactive media: Faraday isolators for high average power lasers"; (4) Cherepashchuk A M (Sternberg Astronomical Institute, Lomonosov Moscow State University, Moscow) "Discovery of gravitational waves: a new chapter in black hole studies"; (5) Lipunov V M (Sternberg Astronomical Institute, Lomonosov Moscow State University, Moscow) "Astrophysical meaning of the discovery of gravitational waves." Papers based on talks 2-5 are published in this issue of the journal. A paper based on talk 1 will be published in a forthcoming issue of Physics-Uspekhi. Additional information on the discovery of gravitational waves, the history of their theoretical prediction, and the advances in possible methods for their investigation can be found on the Physics-Uspekhi site www.ufn.ru, on the page http://ufn.ru/en/events/gravitational_waves_discovery.html dedicated to this outstanding discovery. • The road to the discovery of gravitational waves, V B Braginsky, I A Bilenko, S P Vyatchanin, M L Gorodetskii, V P Mitrofanov, L G Prokhorov, S E Strigin, F Ya Khalili Physics-Uspekhi, 2016, Volume 59, Number 9, Pages 879-885 • Thermooptics of magnetoactive media: Faraday isolators for high average power lasers, E A Khazanov Physics-Uspekhi, 2016, Volume 59, Number 9, Pages 886-909 • Discovery of gravitational waves: a new chapter in black hole studies, A M Cherepashchuk Physics-Uspekhi, 2016, Volume 59, Number 9, Pages 910-917 • Astrophysical meaning of the discovery of gravitational waves, V M Lipunov Physics-Uspekhi, 2016, Volume 59, Number 9, Pages 918-928

After-school setting, physical activity, and sedentary behavior in 5th grade boys and girls.

PubMed

Taverno Ross, S E; Dowda, M; Colabianchi, N; Saunders, R; Pate, R R

2012-09-01

After-school hours are considered critical for children's physical activity (PA) and sedentary behaviors (SB); however, whether the after-school setting influences children's activity patterns is unknown. This study examined the influence of after-school setting (i.e., parent report of the child's usual after-school setting) on 5th grade children's PA and SB, and differences by race/ethnicity. Boys whose parents reported they usually attended an after-school program had higher PA than boys who usually went home after school. A significant interaction between race/ethnicity and after-school setting showed that minority girls whose parents reported they usually attended an after-school program had higher PA and engaged in less SB compared with those who usually went home, whereas the activity patterns of white girls did not differ by after-school setting. Children's usual after-school setting affects their activity patterns; after-school programs may potentially increase PA in boys and minority girls. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Function of Embryonic Stem Cell-expressed RAS (E-RAS), a Unique RAS Family Member, Correlates with Its Additional Motifs and Its Structural Properties.

PubMed

Nakhaei-Rad, Saeideh; Nakhaeizadeh, Hossein; Kordes, Claus; Cirstea, Ion C; Schmick, Malte; Dvorsky, Radovan; Bastiaens, Philippe I H; Häussinger, Dieter; Ahmadian, Mohammad Reza

2015-06-19

E-RAS is a member of the RAS family specifically expressed in embryonic stem cells, gastric tumors, and hepatic stellate cells. Unlike classical RAS isoforms (H-, N-, and K-RAS4B), E-RAS has, in addition to striking and remarkable sequence deviations, an extended 38-amino acid-long unique N-terminal region with still unknown functions. We investigated the molecular mechanism of E-RAS regulation and function with respect to its sequence and structural features. We found that N-terminal extension of E-RAS is important for E-RAS signaling activity. E-RAS protein most remarkably revealed a different mode of effector interaction as compared with H-RAS, which correlates with deviations in the effector-binding site of E-RAS. Of all these residues, tryptophan 79 (arginine 41 in H-RAS), in the interswitch region, modulates the effector selectivity of RAS proteins from H-RAS to E-RAS features. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Climatic Change and Dynamics of Northern Hemisphere Storm-tracks: Changes in Transient Eddies Behavior

NASA Astrophysics Data System (ADS)

Martynova, Yuliya; Krupchatnikov, Vladimir

2013-04-01

An evidence of our understanding of the general circulation is whether we can predict changes in the general circulation that might be associated with past or future climate changes. Changes in the location, intensity or seasonality of major climatological features of the general circulation could be more important than average temperature changes, particularly where these changes could affect local hydrology, energy balances, etc. Under these major climatological features we assume the poleward expansion of the tropical circulation (Hadley circulation), static stability (changes in the vertical temperature structure of the atmosphere), role of SST forcing, sea ice extension, extratropical eddies behavior. We have a question: would the climate change significantly affect the location and intensity of midlatitude storm-tracks and associated jets? Mean-flow interaction in midlatitudes produces low-frequency variations in the latitude of the jets. It is reasonable to think that a modest climate change might significantly affects the jets location and their associated storm tracks. The storm-tracks are defined as the region of strong baroclinicity (maximum meridional temperature gradient), which are determined on the basis of eddy statistics like eddy fluxes of angular momentum, energy, and water (with the use of high-bandpass filter). In the Northern Hemisphere, there are two major storms: in the region of Atlantic and Pacific. The storm-tracks play important role in the dynamics of weather and climate. They affect the global energy cycle and the hydrological cycle, and as a result they bring heavy rains and other hazardous weather phenomena in the middle latitudes. The recent increase in global tropopause heights is closely associated with systematic temperature changes below and above the tropopause. Temperature increases in the troposphere and decreases in the stratosphere. The pattern of warming and cooling also affects the zonal wind structure in the region of the subtropical upper troposphere and lower stratosphere (UTLS). Extratropical tropospheric eddies play a central role in this mechanism. The eddies tend to move eastward with the zonal flow and equatorward toward the subtropics until they reach their critical latitudes, where their phase speed equals the speed of the background zonal flow. This work is partially supported by the Ministry of education and science of the Russian Federation (con-tract #8345), SB RAS project VIII.80.2.1, RFBR grant #11-05-01190a, and integrated project SB RAS #131.

PREFACE: 1st International School and Conference "Saint Petersburg OPEN 2014" on Optoelectronics, Photonics, Engineering and Nanostructures

NASA Astrophysics Data System (ADS)

2014-09-01

Dear Colleagues, 1st International School and Conference "Saint Petersburg OPEN 2014" on Optoelectronics, Photonics, Engineering and Nanostructures was held on March 25 - 27, 2014 at St. Petersburg Academic University - Nanotechnology Research and Education Centre of the Russian Academy of Sciences. The School and Conference included a series of invited talks given by leading professors with the aim to introduce young scientists with actual problems and major advances in physics and technology. The keynote speakers were: Mikhail Glazov (Ioffe Physico-Technical Institute RAS, Russia) Vladimir Dubrovskii (Saint Petersburg Academic University RAS, Russia) Alexey Kavokin (University of Southampton, United Kingdom and St. Petersburg State University, Russia) Vladimir Korenev (Ioffe Physico-Technical Institute RAS, Russia) Sergey Kukushkin (Institute of Problems of Mechanical Engineering RAS, Russia) Nikita Pikhtin (Ioffe Physico-Technical Institute RAS, Russia and "Elfolum" Ltd., Russia) Dmitry Firsov (Saint Petersburg State Polytechnical University, Russia) During the poster session all undergraduate and graduate students attending the conference presented their works. Sufficiently large number of participants with more than 160 student attendees from all over the world allowed the Conference to provide a fertile ground for the fruitful discussions between the young scientists as well as to become a perfect platform for the valuable discussions between student authors and highly experienced scientists. The best student papers, which were selected by the Program Committee and by the invited speakers basing on the theses and their poster presentation, were awarded with diplomas of the conference - see the photos. This year's School and Conference is supported by SPIE (The International Society for Optics and Photonics), OSA (The Optical Society), St. Petersburg State Polytechnical University and by Skolkovo Foundation. It is a continuation of the annual schools and seminars for youth on topical problems of physics and technology that is organized by the Academic University since 2009. We invite all the students and young scientists to attend "Saint Petersburg OPEN" in 2015! Please, find details at http://spbopen2015.spbau.com/ With best wishes, Editorial Board, Program and Organizing Committees

mHealth Technologies to Influence Physical Activity and Sedentary Behaviors: Behavior Change Techniques, Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Direito, Artur; Carraça, Eliana; Rawstorn, Jonathan; Whittaker, Robyn; Maddison, Ralph

2017-04-01

mHealth programs offer potential for practical and cost-effective delivery of interventions capable of reaching many individuals. To (1) compare the effectiveness of mHealth interventions to promote physical activity (PA) and reduce sedentary behavior (SB) in free-living young people and adults with a comparator exposed to usual care/minimal intervention; (2) determine whether, and to what extent, such interventions affect PA and SB levels and (3) use the taxonomy of behavior change techniques (BCTs) to describe intervention characteristics. A systematic review and meta-analysis following PRISMA guidelines was undertaken to identify randomized controlled trials (RCTs) comparing mHealth interventions with usual or minimal care among individuals free from conditions that could limit PA. Total PA, moderate-to-vigorous intensity physical activity (MVPA), walking and SB outcomes were extracted. Intervention content was independently coded following the 93-item taxonomy of BCTs. Twenty-one RCTs (1701 participants-700 with objectively measured PA) met eligibility criteria. SB decreased more following mHealth interventions than after usual care (standardised mean difference (SMD) -0.26, 95 % confidence interval (CI) -0.53 to -0.00). Summary effects across studies were small to moderate and non-significant for total PA (SMD 0.14, 95 % CI -0.12 to 0.41); MVPA (SMD 0.37, 95 % CI -0.03 to 0.77); and walking (SMD 0.14, 95 % CI -0.01 to 0.29). BCTs were employed more frequently in intervention (mean = 6.9, range 2 to 12) than in comparator conditions (mean = 3.1, range 0 to 10). Of all BCTs, only 31 were employed in intervention conditions. Current mHealth interventions have small effects on PA/SB. Technological advancements will enable more comprehensive, interactive and responsive intervention delivery. Future mHealth PA studies should ensure that all the active ingredients of the intervention are reported in sufficient detail.

Results of a Phase 2, Randomized,Vehicle-Controlled Study Evaluating the Efficacy,Tolerability, and Safety of Daily or Twice Daily SB204 for the Treatment of Acne Vulgaris.

PubMed

Eichenfield, Lawrence F; Gold, Linda Stein; Nahm, Walter K; Cook-Bolden, Fran E; Pariser, David M

2016-12-01

This randomized, double-blind, placebo-controlled, Phase 2 study compared efficacy, tolerability, and safety of SB204 once or twice daily to vehicle in the treatment of acne vulgaris. Eligible subjects were to be between 12 and 40 years old, have facial acne vulgaris with 25 to 70 non-inflammatory lesions, 20 to 40 inflammatory lesions, no more than 2 nodules, and a baseline Investigator's Global Assessment (IGA) score of moderate or severe. The co-primary efficacy endpoints were the absolute change in inflammatory and non-inflammatory lesion counts and IGA success rate (baseline to week 12). Safety assessments included reported adverse events (AEs), physical examinations, and laboratory testing. Tolerability was evaluated by the investigators based on the occurrence and severity of erythema, scaling, dryness, pruritus, and burning/stinging. A total of 213 subjects were randomized: 27 subjects to vehicle once daily; 29 subjects to vehicle twice daily; 53 subjects to SB204 2% twice daily; 52 subjects to SB204 4% once daily; and 52 subjects to SB204 4% twice daily. When compared to vehicle, treatment with all 3 SB204 regimens significantly reduced the absolute inflammatory lesion count and SB204 4% once daily reduced the absolute non-inflammatory lesion count. Treatment with SB204 4% once daily demonstrated a significant reduction in percent inflammatory lesions by week 4. There were no significant differences in the IGA success rates between groups at the end of treatment. All treatment regimens of SB204 were found to be safe and well tolerated. When compared to vehicle, SB204 2% and SB204 4% significantly decreased the absolute inflammatory lesion count and SB204 4% once daily also significantly decreased the absolute non-inflammatory lesion count in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 2% and 4% was found to be safe and well tolerated. J Drugs Dermatol. 2016;15(12):1496-1502.

Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T Cells

PubMed Central

Jun, Jesse E.; Rubio, Ignacio; Roose, Jeroen P.

2013-01-01

The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells. PMID:24027568

Joint Use Policies: Are they related to adolescent behavior?

PubMed Central

Chriqui, Jamie; Chaloupka, Frank J.; Johnston, Lloyd

2014-01-01

Objective Joint use policies (JUP) encourage shared facility use, usually between schools and a city or private organization, for both physical activity-related and non-physical activity-related programs. Little is known about JUP’s impact on physical activity (PA). This study examined whether more specific JUPs were associated with increased PA and decreased sedentary behavior (SB) in adolescents. Methods Data on PA, sports participation, and SB were taken from annual cross-sectional nationally representative samples of 51,269 8th, 10th and 12th grade public school students nested in 461 school districts in the US from 2009–2011. JUP measures were constructed using information obtained from corresponding school district JU policies. Multivariable analyses were conducted, controlling for individual demographic and socioeconomic characteristics and clustering at the district level. Results Results showed small associations between more specific JUPs and increased PA (IRR 1.01, 95% CI: 1.00, 1.02). Closer examination of specific JUP provisions indicates that specifying what times facilities are available for use was associated with vigorous exercise and prioritizing school or affiliated organizations’ use and which spaces were available for use were associated with vigorous exercise and more frequent PA participation, which includes participation in sports or athletics. No associations were found between more specific JUPs and SB. Conclusions JUPS may have small influences on adolescent physical activity behavior. Future longitudinal studies should be conducted to examine the impact of JUPs in conjunction with other physical activity-related policies and environmental changes to determine what impact they have on overall adolescent physical activity and sedentary behavior. PMID:25199731

Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

NASA Astrophysics Data System (ADS)

Rodriguez, Jorge H.; Deligkaris, Christos

2013-03-01

Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[ α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N2-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail. Present address: Department of Physics, Drury University

A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.

PubMed

John, Bincy Anu; Xu, Tingting; Ripp, Steven; Wang, Hwa-Chain Robert

2017-02-01

The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research. The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination. Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals. Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the Same Regulatory Sequences.

PubMed

Drosten, Matthias; Simón-Carrasco, Lucía; Hernández-Porras, Isabel; Lechuga, Carmen G; Blasco, María T; Jacob, Harrys K C; Fabbiano, Salvatore; Potenza, Nicoletta; Bustelo, Xosé R; Guerra, Carmen; Barbacid, Mariano

2017-02-01

Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-Ras G12V oncogene sequences. Germline expression of H-Ras G12V or K-Ras G12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes. Whereas H-Ras G12V elicited papillomas and hematopoietic tumors, K-Ras G12V induced lung tumors and gastric lesions. Pulmonary expression of H-Ras G12V created a senescence-like state caused by excessive MAPK signaling. Likewise, H-Ras G12V but not K-Ras G12V induced senescence in mouse embryonic fibroblasts. Label-free quantitative analysis revealed that minor differences in H-Ras G12V expression levels led to drastically different biological outputs, suggesting that subtle differences in MAPK signaling confer nonequivalent functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res; 77(3); 707-18. ©2016 AACR. ©2016 American Association for Cancer Research.

The Tumor Suppressor DiRas3 Forms a Complex with H-Ras and C-RAF Proteins and Regulates Localization, Dimerization, and Kinase Activity of C-RAF*

PubMed Central

Baljuls, Angela; Beck, Matthias; Oenel, Ayla; Robubi, Armin; Kroschewski, Ruth; Hekman, Mirko; Rudel, Thomas; Rapp, Ulf R.

2012-01-01

The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down-regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic effect of DiRas3 is achieved through several mechanisms, including inhibition of cell proliferation, motility, and invasion, as well as induction of apoptosis and autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling through Ras/MAPK and PI3K. Despite intensive research, the mode of interference of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of speculation. In this study, we show that DiRas3 associates with the H-Ras oncogene and that activation of H-Ras enforces this interaction. Furthermore, while associated with DiRas3, H-Ras is able to bind to its effector protein C-RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H-Ras is more stable than the two protein complexes H-Ras·C-RAF or H-Ras·DiRas3, respectively. The consequence of this complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID:22605333

Electronic and optical properties of GaSb:N from first principles

NASA Astrophysics Data System (ADS)

Jadaun, Priyamvada; Nair, Hari; Lordi, Vincenzo; Bank, Seth; Banerjee, Sanjay

2014-03-01

We present an ab-initio study of dilute nitride III-Vs, focusing on dilute nitride GaSb (GaSb:N). GaSb:N displays promise towards realization of optoelectronic devices accessing the mid-infrared wavelength regime. Theoretical and experimental results on its electronic and optical properties are however few. To address this, we present a first principles, density functional theory study using the hybrid HSE06 exchange-correlation functional of GaSb doped with 1.6% nitrogen. We conduct a comparative study on GaAs:N, also with 1.6% nitrogen mole fraction, and find that GaSb:N has a smaller band gap and displays more band gap bowing than GaAs:N. In addition we examine the orbital character of the bands, finding the lowest conduction band to be quasi-delocalized, with a large N-3s contribution. At high concentrations, the N atoms interact via the host matrix, forming a dispersive band of their own which governs optoelectronic properties and dominates band gap bowing. While this band drives the optical and electronic properties of GaSb:N, its physics is not captured by traditional models for dilute-nitrides. We thus propose that a complete theory of dilute-nitrides should incorporate orbital character examination, especially at high N concentrations. Texas Advanced Computing Center (TACC), U.S. Department of Energy, Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

Effect of rhythmic auditory stimulation on gait performance in children with spastic cerebral palsy.

PubMed

Kwak, Eunmi Emily

2007-01-01

The purpose of this study was to use Rhythmic Auditory Stimulation (RAS) for children with spastic cerebral palsy (CP) in a clinical setting in order to determine its effectiveness in gait training for ambulation. RAS has been shown to improve gait performance in patients with significant gait deficits. All 25 participants (6 to 20 years old) had spastic CP and were ambulatory, but needed to stabilize and gain more coordinated movement. Participants were placed in three groups: the control group, the therapist-guided training (TGT) group, and the self-guided training (SGT) group. The TGT group showed a statistically significant difference in stride length, velocity, and symmetry. The analysis of the results in SGT group suggests that the self-guided training might not be as effective as therapist-guided depending on motivation level. The results of this study support three conclusions: (a) RAS does influence gait performance of people with CP; (b) individual characteristics, such as cognitive functioning, support of parents, and physical ability play an important role in designing a training application, the effectiveness of RAS, and expected benefits from the training; and (c) velocity and stride length can be improved by enhancing balance, trajectory, and kinematic stability without increasing cadence.

Application of Molecular Interaction Volume Model for Phase Equilibrium of Sn-Based Binary System in Vacuum Distillation

NASA Astrophysics Data System (ADS)

Kong, Lingxin; Yang, Bin; Xu, Baoqiang; Li, Yifu

2014-09-01

Based on the molecular interaction volume model (MIVM), the activities of components of Sn-Sb, Sb-Bi, Sn-Zn, Sn-Cu, and Sn-Ag alloys were predicted. The predicted values are in good agreement with the experimental data, which indicate that the MIVM is of better stability and reliability due to its good physical basis. A significant advantage of the MIVM lies in its ability to predict the thermodynamic properties of liquid alloys using only two parameters. The phase equilibria of Sn-Sb and Sn-Bi alloys were calculated based on the properties of pure components and the activity coefficients, which indicates that Sn-Sb and Sn-Bi alloys can be separated thoroughly by vacuum distillation. This study extends previous investigations and provides an effective and convenient model on which to base refining simulations for Sn-based alloys.

Giant supercurrent states in a superconductor-InAs/GaSb-superconductor junction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xiaoyan, E-mail: xshi@sandia.gov; Pan, W.; Hawkins, S. D.

2015-10-07

Superconductivity in topological materials has attracted a great deal of interest in both electron physics and material sciences since the theoretical predictions that Majorana fermions can be realized in topological superconductors. Topological superconductivity could be realized in a type II, band-inverted, InAs/GaSb quantum well if it is in proximity to a conventional superconductor. Here, we report observations of the proximity effect induced giant supercurrent states in an InAs/GaSb bilayer system that is sandwiched between two superconducting tantalum electrodes to form a superconductor-InAs/GaSb-superconductor junction. Electron transport results show that the supercurrent states can be preserved in a surprisingly large temperature-magnetic fieldmore » (T – H) parameter space. In addition, the evolution of differential resistance in T and H reveals an interesting superconducting gap structure.« less

Band gap tuning and optical absorption in type-II InAs/GaSb mid infrared short period superlattices: 14 bands K Dot-Operator p study

DOE Office of Scientific and Technical Information (OSTI.GOV)

AbuEl-Rub, Khaled M.

2012-09-06

The MBE growth of short-period InAs/GaSb type-II superlattice structures, varied around 20.5 A InAs/24 A GaSb were [J. Applied physics, 96, 2580 (2004)] carried out by Haugan et al. These SLs were designed to produce devices with an optimum mid-infrared photoresponse and a sharpest photoresponse cutoff. We have used a realistic and reliable 14-band k.p formalism description of the superlattice electronic band structure to calculate the absorption coefficient in such short-period InAs/GaSb type-II superlattices. The parameters for this formalism are known from fitting to independent experiments for the bulk materials. The band-gap energies are obtained without any fitting parameters, andmore » are in good agreement with experimental data.« less

The section TiInSe/sub 2/-TiSbSe/sub 2/ of the system Ti-In-Sb-Se

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guseinov, G.D.; Chapanova, L.M.; Mal'sagov, A.U.

1985-09-01

The ternary compounds A /SUP I/ B /SUP III/ C/sub 2/ /SUP VI/ (A /SUP I/ is univalent Ti; B /SUP III/ is Ga or In; and C /SUP VI/ is S, Se or Te) form a class of semiconductors with a large number of different gap widths. The compounds crystallize in the chalcopyrite structure. Solid solutions based on these compounds, which permit varying smoothly the gap width and other physical parameters over wide limits, are of great interest. The authors synthesized the compounds TiInSe/sub 2/ and TiSbSe/sub 2/ from the starting materials Ti-000, In-000, Sb-000 and Se-OSCh-17-4 by directmore » fusion of the components, taken in a stoichiometric ratio, in quartz ampules evacuated to 1.3 X 10/sup -3/ Pa and sealed.« less

A distinct class of dominant negative Ras mutants: cytosolic GTP-bound Ras effector domain mutants that inhibit Ras signaling and transformation and enhance cell adhesion.

PubMed

Fiordalisi, James J; Holly, Stephen P; Johnson, Ronald L; Parise, Leslie V; Cox, Adrienne D

2002-03-29

Cytosolic GTP-bound Ras has been shown to act as a dominant negative (DN) inhibitor of Ras by sequestering Raf in non-productive cytosolic complexes. Nevertheless, this distinct class of DN mutants has been neither well characterized nor extensively used to analyze Ras signaling. In contrast, DN Ras17N, which functions by blocking Ras guanine nucleotide exchange factors, has been well characterized and is widely used. Cytosolic GTP-bound Ras mutants could be used to inhibit particular Ras effectors by introducing additional mutations (T35S, E37G or Y40C) that permit them to associate selectively with and inhibit Raf, RalGDS, or phosphoinositide 3-kinase, respectively. When the wild-type Ras effector binding region is used, cytosolic Ras should associate with all Ras effectors, even those that are not yet identified, making these DN Ras mutants effective inhibitors of multiple Ras functions. We generated cytosolic GTP-bound H-, N-, and K-Ras, and we assessed their ability to inhibit Ras-induced phenotypes. In fibroblasts, cytosolic H-, N-, and K-Ras inhibited Ras-induced Elk-1 activation and focus formation, induced a flattened cell morphology, and increased adhesion to fibronectin through modulation of a beta(1)-subunit-containing integrin, thereby demonstrating that DN activity is not limited to a subset of Ras isoforms. We also generated cytosolic GTP-bound Ras effector domain mutants (EDMs), each of which reduced the ability of cytosolic GTP-bound Ras proteins to inhibit Elk-1 activation and to induce cell flattening, implicating multiple pathways in these phenotypes. In contrast, Ras-induced focus formation, platelet-derived growth factor (PDGF)-, or Ras-induced phospho-Akt levels and cell adhesion to fibronectin were affected by T35S and Y40C EDMs, whereas PDGF- or Ras-induced phospho-Erk levels were affected only by the T35S EDM, implying that a more limited set of Ras-mediated pathways participate in these phenotypes. These data constitute the first extensive characterization of this functionally distinct class of DN Ras inhibitor proteins.

Temperature-driven topological quantum phase transitions in a phase-change material Ge2Sb2Te5.

PubMed

Eremeev, S V; Rusinov, I P; Echenique, P M; Chulkov, E V

2016-12-13

The Ge 2 Sb 2 Te 5 is a phase-change material widely used in optical memory devices and is a leading candidate for next generation non-volatile random access memory devices which are key elements of various electronics and portable systems. Despite the compound is under intense investigation its electronic structure is currently not fully understood. The present work sheds new light on the electronic structure of the Ge 2 Sb 2 Te 5 crystalline phases. We demonstrate by predicting from first-principles calculations that stable crystal structures of Ge 2 Sb 2 Te 5 possess different topological quantum phases: a topological insulator phase is realized in low-temperature structure and Weyl semimetal phase is a characteristic of the high-temperature structure. Since the structural phase transitions are caused by the temperature the switching between different topologically non-trivial phases can be driven by variation of the temperature. The obtained results reveal the rich physics of the Ge 2 Sb 2 Te 5 compound and open previously unexplored possibility for spintronics applications of this material, substantially expanding its application potential.

A new quaternary semiconductor compound (Ba2Sb4GeS10): Ab initio study

NASA Astrophysics Data System (ADS)

Ozisik, Havva Bogaz; Ozisik, Haci; Deligoz, Engin

2017-03-01

The newly synthesised Ba2Sb4GeS10 compound is notable because of the interesting features of the quaternary Sb-containing materials. The first principle method has been used to determine the physical properties of this compound. In particular, the electronic structure has been analysed using both conventional GGA-PBE and HSE06 functional. The values of the band gap for PBE and HSE06 calculations were 1.324 and 1.84 eV, respectively. The calculated elastic constants were used to predict polycrystalline mechanical properties. The estimated Vickers hardness (2.7 GPa) values show that Ba2Sb4GeS10 is soft matter. Moreover, the vibrational properties of the compound have been studied. The calculation of the elastic constants and phonon dispersion curves indicates that the Ba2Sb4GeS10 compound is stable both mechanically and dynamically. Furthermore, the minimum thermal conductivity and optical properties, such as dielectric functions and energy loss function, have also been discussed in detail in this paper.

Nanodopant-Induced Band Modulation in AgPbmSbTe2+m-Type Nanocomposites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yi; Ke, Xuezhi; Chen, Changfeng

2011-01-01

We elucidate the fundamental physics of nanoscale dopants in narrow band-gap thermoelectric nanocomposites XPbmYTe2+m (X=Ag,Na; Y=Sb,Bi) using first-principles calculations. Our re- sults unveil distinct band-structure modulations, most notably a sizable band-gap widening driven by nanodopant-induced lattice strain and a band split-off at the conduction band minimum caused by the spin-orbit interaction of the dopant Sb or Bi atoms. Boltzmann transport calculations demon- strate that these band modulations have significant but competing effects on high-temperature elec- tron transport behavior. These results offer insights for understanding recent experimental findings and suggest principles for optimizing thermoelectric properties of narrow band-gap semiconductors.

Electrodeposition of zinc antimony alloy thermoelectric materials

NASA Astrophysics Data System (ADS)

Hairin, A. L. N.; Romainor, M. N.; Othman, R.; Daud, F. D. M.

2018-01-01

Zinc antimonite, Zn4Sb3 is a promising thermoelectric material because of its high thermoelectric performance and abundance of Zn and Sb in nature. Thus, in this study, samples of Zn-Sb alloy were prepared using electrodeposition method because of its simple experimental set-up, which also carried out in the room temperature. From the XRD results, all samples deposited exhibit Zn-Sb alloy compositions. The best results were S1 and S3 as they had dominant peaks that showed the crystal lattice of Zn4Sb3. From the SEM images, the surface morphology of Zn-Sb alloy deposited samples showed were all-irregular, course and rough structures. While, the atoms arrangement of the deposited samples were all flowery-like. Based on physical properties characterization, the best samples; S1 (0.1M ZnCl2-0.1M SbCl3, 100mA, 120min) and S3 (0.1M ZnCl2-0.1M SbCl3, 50mA, 120min), were selected and investigated their thermoelectric performances; electrical conductivity and Seebeck coefficient, to determine their power factor, PF. Heat capacity of the samples was also examined to relate it with thermal conductivity of Zn-Sb deposited samples. For thermoelectric performance, S1 obtained power factor of 1.37x10-7V/K. Ω.cm at 102°C with the Seebeck coefficient of 181μV/K. While as for S3, the power factor was 1.58x10-7V/K. Ω.cm with Seebeck coefficient of 113μV/K at 101°C. From DSC analysis, it showed that S3 obtained higher Cp than S1. Cp for S3 was 46.8093mJ/°C while S1 was 38.3722mJ/°C.

Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission

PubMed Central

van der Hoeven, Dharini; Cho, Kwang-jin; Ma, Xiaoping; Chigurupati, Sravanthi; Parton, Robert G.

2013-01-01

Ras proteins regulate signaling pathways important for cell growth, differentiation, and survival. Oncogenic mutant Ras proteins are commonly expressed in human tumors, with mutations of the K-Ras isoform being most prevalent. To be active, K-Ras must undergo posttranslational processing and associate with the plasma membrane. We therefore devised a high-content screening assay to search for inhibitors of K-Ras plasma membrane association. Using this assay, we identified fendiline, an L-type calcium channel blocker, as a specific inhibitor of K-Ras plasma membrane targeting with no detectable effect on the localization of H- and N-Ras. Other classes of L-type calcium channel blockers did not mislocalize K-Ras, suggesting a mechanism that is unrelated to calcium channel blockade. Fendiline did not inhibit K-Ras posttranslational processing but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus, endosomes, and cytosol. Fendiline significantly inhibited signaling downstream of constitutively active K-Ras and endogenous K-Ras signaling in cells transformed by oncogenic H-Ras. Consistent with these effects, fendiline blocked the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Taken together, these results suggest that inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras-specific anticancer therapeutics. PMID:23129805

Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

PubMed Central

Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

2015-01-01

The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

Involvement of H- and N-Ras isoforms in transforming growth factor-{beta}1-induced proliferation and in collagen and fibronectin synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez-Salgado, Carlos; Fuentes-Calvo, Isabel; Instituto 'Reina Sofia' de Investigacion Nefrologica, Universidad de Salamanca, 37007 Salamanca

2006-07-01

Transforming growth factor {beta}1 (TGF-{beta}1) has a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-{beta} and Ras signaling pathways are closely related: TGF-{beta}1 overcomes Ras mitogenic effects and Ras counteracts TGF-{beta} signaling. Tubule-interstitial fibrosis is associated to increases in Ras, Erk, and Akt activation in a renal fibrosis model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras effectors Erk and Akt, in TGF-{beta}1-mediated extracellular matrix (ECM) synthesis and proliferation, using embrionary fibroblasts from double knockout (KO) mice for H- and N-Ras (H-ras {sup -/-}/N-ras {sup -/-}) isoforms andmore » from heterozygote mice (H-ras {sup +/-}/N-ras {sup +/-}). ECM synthesis is increased in basal conditions in H-ras {sup -/-}/N-ras {sup -/-} fibroblasts, this increase being higher after stimulation with TGF-{beta}1. TGF-{beta}1-induced fibroblast proliferation is smaller in H-ras {sup -/-}/N-ras {sup -/-} than in H-ras {sup +/-}/N-ras {sup +/-} fibroblasts. Erk activation is decreased in H-ras {sup -/-}/N-ras {sup -/-} fibroblasts; inhibition of Erk activation reduces fibroblast proliferation. Akt activation is higher in double KO fibroblasts than in heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation may be involved in the increase in ECM synthesis observed in the absence of H- and N-Ras.« less

[Study on the infection of taiga ticks with Borrelia in the territory of Novosibirsk Scientific Center SB PAS].

PubMed

Borgoiakov, V Iu; Fomenko, N V; Panov, V V; Chikova, E D

2010-01-01

In our study, Borrelia were revealed in the taiga ticks Ixodes persulcatus collected on vegetation by flagging, as well as in the ticks removed from the people who asked for help in the vaccination center located in the Novosibirsk Scientific Center of the Siberian Branch of Russian Academy of Science (NS SB RAS). By the isolation of Borrelia on BSK-H medum, the occurrence of B. garinii, B. afzelii, and B. miyamotoi was established in the territory of NSC. B. miyamotoi isolates were unstable and lost their ability to growth in later passages. DNA of the same three species of Borrelia was detected by PCR in the samples of ticks, both collected on vegetation by flagging and removed from humans. DNA of B. garinii was recorded most often; DNA of B. afzelii was less frequent; and the least number of positive samples was shown for B. miyamotoi. In the ticks collected on vegetation by flagging, DNA of B. garinii was found in 38.6%, B. afzelii in 9.9%, and B. miyamoboi in 3.9% of samples. In the ticks removed from people, number of positive samples was lesser; so, DNA of B. garinii was detected in 24.2%, B. afzelii in 6.9%, and B. miyamotoi in 5.6% of samples. Mixed infection with two Borrelia species was recorded, and DNA of B. mivamnotoi more often detected simultaneously with DNA of B. garinii.

Structure evolution upon chemical and physical pressure in (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tiittanen, T.; Karppinen, M., E-mail: maarit.karppinen@aalto.fi

Here we demonstrate the gradual structural transformation from the monoclinic I2/m to tetragonal I4/m, cubic Fm-3m and hexagonal P6{sub 3}/mmc structure upon the isovalent larger-for-smaller A-site cation substitution in the B-site ordered double-perovskite system (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6}. This is the same transformation sequence previously observed up to Fm-3m upon heating the parent Sr{sub 2}FeSbO{sub 6} phase to high temperatures. High-pressure treatment, on the other hand, transforms the hexagonal P6{sub 3}/mmc structure of the other end member Ba{sub 2}FeSbO{sub 6} back to the cubic Fm-3m structure. Hence we may conclude that chemical pressure, physical pressure and decreasing temperature allmore » work towards the same direction in the (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6} system. Also shown is that with increasing Ba-for-Sr substitution level, i.e. with decreasing chemical pressure effect, the degree-of-order among the B-site cations, Fe and Sb, decreases. - Graphical abstract: In the (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6} double-perovskite system the gradual structural transformation from the monoclinic I2/m to tetragonal I4/m, cubic Fm-3m and hexagonal P6{sub 3}/mmc structure is seen upon the isovalent larger-for-smaller A-site cation substitution. High-pressure treatment under 4 GPa extends stability of the cubic Fm-3m structure within a wider substitution range of x. - Highlights: • Gradual structural transitions upon A-cation substitution in (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6.} • With increasing x structure changes from I2/m to I4/m, Fm-3m and P6{sub 3}/mmc. • Degree of B-site order decreases with increasing x and A-site cation radius. • High-pressure treatment extends cubic Fm-3m phase stability for wider x range. • High-pressure treatment affects bond lengths mostly around the A-cation.« less

Local Structure of Sb in Cretaceous-Tertiary Boundary Clays from Stevns Klint By the XAFS Method

NASA Astrophysics Data System (ADS)

Hongu, H.; Yoshiasa, A.; Tobase, T.; Hiratoko, T.; Isobe, H.; Arima, H.; Sugiyama, K.; Okube, M.

2014-12-01

The Cretaceous-Tertiary (K-T) mass extinctions has been thought to be due to the asteroid impact since Ir anomalies was found by Alvarez et al. (1980) . The boundary clay is also enriched in Cr, Co, Ni, Cu, Zn, As and Sb. Especially concentrations of Sb and As are unusually large. However, the origins and concentration processes of Sb are unknown. In this study, local structure around antimony atoms in K-T boundary clay from Stevns Klint, Denmark, was determined by Sb K-edge XAFS spectroscopy. The XAFS analyses give the information about the chemical state and coordination environment around Sb atoms and help identify of the concentration phase, and also may provide various kinds of information about the asteroid impact and mass extinction. The XAFS measurements were performed at the BL-NW10A beamline at the Photon Factory in KEK, Tsukuba, Japan. The XANES spectra and radial structure function (RSF) showed that Sb in K-T boundary clays is high oxidation state Sb5+ and occupies a SbO6 octahedral site. The Sb-O interatomic distance in K-T clay sample is 2.08(1) A. It is known that Sb5+ is stable form in soil and soil water under an equilibrium situation within the Earth's surface environment. Antimony belongs to group 15 in the periodic table below arsenic, and the chemical behavior of Sb5+ is similar to that of As5+. Because there is a close correlation on co-precipitation between As and Fe (Ebihara and Miura, 1996; Sakai et al., 2007) , it is considered that Sb also correlates closely with Fe compounds (e.g., ferric hydroxides). Abundant ferric hydroxides occur in K-T boundary clays. It is considered that one of the reasons of abnormal high concentrations of Sb and As in K-T boundary clays is a lot of dust from impact ejecta falls with iron ions and deposits on surface of the Earth for a short period of time after the asteroid impact. ReferencesL. W. Alvarez, Science, 208, 1095-1108 (1980) M. Ebihara and T. Miura, Geochimica et Cosmochimica Acta, 60, 5133-5144 (1996) S. Sakai et al., The American Institute of Physics, Conference Proceeding, 882, 274-276 (2007)

What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

PubMed

Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

2010-06-11

Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd. All rights reserved.

RasGRP3 regulates the migration of glioma cells via interaction with Arp3

PubMed Central

Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Poisson, Laila M.; Blumberg, Peter M.; Brodie, Chaya

2015-01-01

Glioblastoma (GBM), the most aggressive primary brain tumors, are highly infiltrative. Although GBM express high Ras activity and Ras proteins have been implicated in gliomagenesis, Ras-activating mutations are not frequent in these tumors. RasGRP3, an important signaling protein responsive to diacylglycerol (DAG), increases Ras activation. Here, we examined the expression and functions of RasGRP3 in GBM and glioma cells. RasGRP3 expression was upregulated in GBM specimens and glioma stem cells compared with normal brains and neural stem cells, respectively. RasGRP3 activated Ras and Rap1 in glioma cells and increased cell migration and invasion partially via Ras activation. Using pull-down assay and mass spectroscopy we identified the actin-related protein, Arp3, as a novel interacting protein of RasGRP3. The interaction of RasGRP3 and Arp3 was validated by immunofluorescence staining and co-immunoprecipitation, and PMA, which activates RasGRP3 and induces its translocation to the peri-nuclear region, increased the association of Arp3 and RasGRP3. Arp3 was upregulated in GBM, regulated cell spreading and migration and its silencing partially decreased these effects of RasGRP3 in glioma cells. In summary, RasGRP3 acts as an important integrating signaling protein of the DAG and Ras signaling pathways and actin polymerization and represents an important therapeutic target in GBM. PMID:25682201

Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: modulation of cell survival and migration.

PubMed

Pamonsinlapatham, Perayot; Gril, Brunilde; Dufour, Sylvie; Hadj-Slimane, Réda; Gigoux, Véronique; Pethe, Stéphanie; L'hoste, Sébastien; Camonis, Jacques; Garbay, Christiane; Raynaud, Françoise; Vidal, Michel

2008-11-01

Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras. We used confocal microscopy to analyze our stably transfected cell model producing mutant Ras (PC3Ras(V12)). Staining for RasGAP-SH3/Capns1 co-localization was two-fold stronger in the protrusions of Ras(V12) cells than in PC3 cells. RasGAP or Capns1 knockdown in PC3Ras(V12) cells induced a two- to three-fold increase in apoptosis. Capns1 gene silencing reduced the speed and increased the persistence of movement in PC3Ras(V12) cells. In contrast, RasGAP knockdown in PC3Ras(V12) cells increased cell migration. Knockdown of both proteins altered the speed and directionality of cell motility. Our findings suggest that RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival.

Mutation-Specific RAS Oncogenicity Explains N-RAS Codon 61 Selection in Melanoma

PubMed Central

Burd, Christin E.; Liu, Wenjin; Huynh, Minh V.; Waqas, Meriam A.; Gillahan, James E.; Clark, Kelly S.; Fu, Kailing; Martin, Brit L.; Jeck, William R.; Souroullas, George P.; Darr, David B.; Zedek, Daniel C.; Miley, Michael J.; Baguley, Bruce C.; Campbell, Sharon L.

2014-01-01

N-RAS mutation at codon 12, 13 or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an N-RasQ61R knock-in allele to similarly designed K-RasG12D and N-RasG12D alleles. With concomitant p16INK4a inactivation, K-RasG12D or N-RasQ61R expression efficiently promoted melanoma in vivo, whereas N-RasG12D did not. Additionally, N-RasQ61R mutation potently cooperated with Lkb1/Stk11 loss to induce highly metastatic disease. Functional comparisons of N-RasQ61R and N-RasG12D revealed little difference in the ability of these proteins to engage PI3K or RAF. Instead, N-RasQ61R showed enhanced nucleotide binding, decreased intrinsic GTPase activity and increased stability when compared to N-RasG12D. This work identifies a faithful model of human N-RAS mutant melanoma, and suggests that the increased melanomagenecity of N-RasQ61R over N-RasG12D is due to heightened abundance of the active, GTP-bound form rather than differences in the engagement of downstream effector pathways. PMID:25252692

K-Ras Populates Conformational States Differently from Its Isoform H-Ras and Oncogenic Mutant K-RasG12D.

PubMed

Parker, Jillian A; Volmar, Alicia Y; Pavlopoulos, Spiro; Mattos, Carla

2018-06-05

Structures of wild-type K-Ras from crystals obtained in the presence of guanosine triphosphate (GTP) or its analogs have remained elusive. Of the K-Ras mutants, only K-RasG12D and K-RasQ61H are available in the PDB representing the activated form of the GTPase not in complex with other proteins. We present the crystal structure of wild-type K-Ras bound to the GTP analog GppCH 2 p, with K-Ras in the state 1 conformation. Signatures of conformational states obtained by one-dimensional proton NMR confirm that K-Ras has a more substantial population of state 1 in solution than H-Ras, which predominantly favors state 2. The oncogenic mutant K-RasG12D favors state 2, changing the balance of conformational states in favor of interactions with effector proteins. Differences in the population of conformational states between K-Ras and H-Ras, as well as between K-Ras and its mutants, can provide a structural basis for focused targeting of the K-Ras isoform in cancer-specific strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Faceting, composition and crystal phase evolution in III-V antimonide nanowire heterostructures revealed by combining microscopy techniques.

PubMed

Xu, Tao; Dick, Kimberly A; Plissard, Sébastien; Nguyen, Thanh Hai; Makoudi, Younes; Berthe, Maxime; Nys, Jean-Philippe; Wallart, Xavier; Grandidier, Bruno; Caroff, Philippe

2012-03-09

III-V antimonide nanowires are among the most interesting semiconductors for transport physics, nanoelectronics and long-wavelength optoelectronic devices due to their optimal material properties. In order to investigate their complex crystal structure evolution, faceting and composition, we report a combined scanning electron microscopy (SEM), transmission electron microscopy (TEM), and scanning tunneling microscopy (STM) study of gold-nucleated ternary InAs/InAs(1-x)Sb(x) nanowire heterostructures grown by molecular beam epitaxy. SEM showed the general morphology and faceting, TEM revealed the internal crystal structure and ternary compositions, while STM was successfully applied to characterize the oxide-free nanowire sidewalls, in terms of nanofaceting morphology, atomic structure and surface composition. The complementary use of these techniques allows for correlation of the morphological and structural properties of the nanowires with the amount of Sb incorporated during growth. The addition of even a minute amount of Sb to InAs changes the crystal structure from perfect wurtzite to perfect zinc blende, via intermediate stacking fault and pseudo-periodic twinning regimes. Moreover, the addition of Sb during the axial growth of InAs/InAs(1-x)Sb(x) heterostructure nanowires causes a significant conformal lateral overgrowth on both segments, leading to the spontaneous formation of a core-shell structure, with an Sb-rich shell.

Physical Androgyny and Cognitive Functioning in Adolescence

ERIC Educational Resources Information Center

Petersen, Anne C.

1976-01-01

This study investigated the relationship of physical manifestations of sex hormone influence to cognitive functioning in a longitudinal sample of 106 adolescent males and 99 females (ages 13, 16, and 18 years). Analyses of the 35 males and 40 females who had all cognitive and physical data at all three ages are reported here. (Author/SB)

Effects of Varying Epoch Lengths, Wear Time Algorithms, and Activity Cut-Points on Estimates of Child Sedentary Behavior and Physical Activity from Accelerometer Data.

PubMed

Banda, Jorge A; Haydel, K Farish; Davila, Tania; Desai, Manisha; Bryson, Susan; Haskell, William L; Matheson, Donna; Robinson, Thomas N

2016-01-01

To examine the effects of accelerometer epoch lengths, wear time (WT) algorithms, and activity cut-points on estimates of WT, sedentary behavior (SB), and physical activity (PA). 268 7-11 year-olds with BMI ≥ 85th percentile for age and sex wore accelerometers on their right hips for 4-7 days. Data were processed and analyzed at epoch lengths of 1-, 5-, 10-, 15-, 30-, and 60-seconds. For each epoch length, WT minutes/day was determined using three common WT algorithms, and minutes/day and percent time spent in SB, light (LPA), moderate (MPA), and vigorous (VPA) PA were determined using five common activity cut-points. ANOVA tested differences in WT, SB, LPA, MPA, VPA, and MVPA when using the different epoch lengths, WT algorithms, and activity cut-points. WT minutes/day varied significantly by epoch length when using the NHANES WT algorithm (p < .0001), but did not vary significantly by epoch length when using the ≥ 20 minute consecutive zero or Choi WT algorithms. Minutes/day and percent time spent in SB, LPA, MPA, VPA, and MVPA varied significantly by epoch length for all sets of activity cut-points tested with all three WT algorithms (all p < .0001). Across all epoch lengths, minutes/day and percent time spent in SB, LPA, MPA, VPA, and MVPA also varied significantly across all sets of activity cut-points with all three WT algorithms (all p < .0001). The common practice of converting WT algorithms and activity cut-point definitions to match different epoch lengths may introduce significant errors. Estimates of SB and PA from studies that process and analyze data using different epoch lengths, WT algorithms, and/or activity cut-points are not comparable, potentially leading to very different results, interpretations, and conclusions, misleading research and public policy.

Examining Influences of Parenting Styles and Practices on Physical Activity and Sedentary Behaviors in Latino Children in the United States: Integrative Review.

PubMed

Lindsay, Ana Cristina; Wasserman, Minerva; Muñoz, Mario A; Wallington, Sherrie F; Greaney, Mary L

2018-01-30

Research indicates that parents influence their children's physical activity (PA) and sedentary behaviors (SB) through their parenting styles and practices. The objectives of this paper were to evaluate existing research examining the associations between parenting styles, parenting practices, and PA and SB among Latino children aged between 2 and 12 years, highlight limitations of the existing research, and generate suggestions for future research. The method of this integrative review was informed by methods developed by Whittemore and Knafl, which allow for the inclusion of qualitative, quantitative, and mixed-methods studies. Using the Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines, five electronic academic databases (PubMed, SPORTDiscus, PsycINFO, PsycARTICLES, and CINAHL) were searched for peer-reviewed, full-text papers published in English. Of the 641 unique citations identified, 67 full-text papers were retrieved, and 16 were selected for review. The majority of the 16 reviewed studies were conducted with predominantly Mexican American or Mexican immigrant samples, and only 1 study examined the association between parenting styles and Latino children's PA and SB. Most (n=15) reviewed studies assessed the influence of parenting practices on children's PA and SB, and they provide good evidence that parenting practices such as offering verbal encouragement, prompting the child to be physically active, providing logistic support, engaging and being involved in PA, monitoring, and offering reinforcement and rewards encourage, facilitate, or increase children's PA. The examined studies also provide evidence that parenting practices, such as setting rules and implementing PA restrictions due to safety concerns, weather, and using psychological control discourage, hinder, or decrease children's PA. Because this review found a very small number of studies examining the relationship between parenting styles and Latino children's PA and SB, additional research is needed. Given that the majority of reviewed studies were conducted with predominantly Mexican American or Mexican immigrant samples, additional research examining parenting styles, parenting practices, and PA and SB among multiethnic Latino groups is needed to design interventions tailored to the needs of this ethnically diverse population group. ©Ana Cristina Lindsay, Minerva Wasserman, Mario A Muñoz, Sherrie F Wallington, Mary L Greaney. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 30.01.2018.

A cluster-randomized controlled trial to reduce sedentary behavior and promote physical activity and health of 8-9 year olds: the Transform-Us! study.

PubMed

Salmon, Jo; Arundell, Lauren; Hume, Clare; Brown, Helen; Hesketh, Kylie; Dunstan, David W; Daly, Robin M; Pearson, Natalie; Cerin, Ester; Moodie, Marj; Sheppard, Lauren; Ball, Kylie; Bagley, Sarah; Paw, Mai Chin A; Crawford, David

2011-10-04

Physical activity (PA) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior (SB) may be detrimental to children's health independent of PA. The primary aim of the Transform-Us! study is to determine whether an 18-month, behavioral and environmental intervention in the school and family settings results in higher levels of PA and lower rates of SB among 8-9 year old children compared with usual practice (post-intervention and 12-months follow-up). The secondary aims are to determine the independent and combined effects of PA and SB on children's cardio-metabolic health risk factors; identify the factors that mediate the success of the intervention; and determine whether the intervention is cost-effective. A four-arm cluster-randomized controlled trial (RCT) with a 2 × 2 factorial design, with schools as the unit of randomization. Twenty schools will be allocated to one of four intervention groups, sedentary behavior (SB-I), physical activity (PA-I), combined SB and PA (SB+PA-I) or current practice control (C), which will be evaluated among approximately 600 children aged 8-9 years in school year 3 living in Melbourne, Australia. All children in year 3 at intervention schools in 2010 (8-9 years) will receive the intervention over an 18-month period with a maintenance 'booster' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessments. To maximize the sample and to capture new students arriving at intervention and control schools, recruitment will be on-going up to the post-intervention time point. Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey. To our knowledge, Transform-Us! is the first RCT to examine the effectiveness of intervention strategies for reducing children's overall sedentary time, promoting PA and optimizing health outcomes. The integration of consistent strategies and messages to children from teachers and parents in both school and family settings is a critical component of this study, and if shown to be effective, may have a significant impact on educational policies as well as on pedagogical and parenting practices. ACTRN12609000715279; Current Controlled Trials ISRCTN83725066.

Metamorphic InAsSb/AlInAsSb Heterostructures for Optoelectronic Applications

DTIC Science & Technology

2013-03-20

respectively. VC 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4796181] The development of highly efficient light emitting devi...C12 elastic constants 14 and the standard relationship between strains in perpendicular directions (e ¼ 2 c12c11 ejj) 15 we deter- mined the residual...line as the cloud of reflexes from the pseudomorphic part of the compositionally graded buffers. To obtain information about electroluminescence char

Outdoor play in children: associations with objectively-measured physical activity, sedentary behavior and weight status.

PubMed

Stone, Michelle R; Faulkner, Guy E J

2014-08-01

To determine the amount of time children play outdoors and examine associations with weekday, weekend and after-school physical activity (PA), sedentary behavior (SB), and weight-status (normal-weight, overweight/obese). Data were extracted from Project BEAT (Toronto, 2010-2011; www.beat.utoronto.ca). Children's (n=856; mean age=11±0.6years) PA and SB were measured using accelerometry. Outdoor play (OP) was assessed via parental report and collapsed into three categories (<1h/day, 1-2h/day, >2h/day) and differences in anthropometric and PA characteristics were assessed. 55.1%, 37.2%, and 7.7% of children played outdoors for <1h/day, 1-2h/day and >2h/day, respectively, on weekdays. OP was higher on weekends and in boys. OP was associated with SB, light PA and MVPA at all time-points, whereby children attaining <1h/day had lower activity profiles. Boys playing outdoors for <1h/day were more likely to be overweight/obese and had lower PA levels than normal weight boys. However, overweight/obese boys who spent >2h/day playing outdoors had PA profiles similar to normal weight counterparts. Encouraging children to spend more time outdoors may be an effective strategy for increasing PA, reducing SB, and preventing excess weight gain (particularly boys' play). Copyright © 2014 Elsevier Inc. All rights reserved.

The intellectual profile of abused and neglected children in the Philippines: An analysis of SB5 IQ scores of sexually abused, physically abused and neglected children.

PubMed

Bengwasan, Peejay D

2018-05-24

Child abuse and neglect have been associated with cognitive deficits, among other effects on child development. This study explores the prediction that child abuse and neglect has an impact on Stanford-Binet Intelligence Scales 5th Edition (SB5) IQ scores, in relation to gender, age and type of abuse experienced. 300 children with experiences of abuse and neglect were included in the study, comprising 100 sexually abused, 100 physically abused and 100 neglected children. Overall, all scores on the SB5 were found to be significantly lower than the minimum average scores on the test. Verbal IQ (VIQ) scores were likewise found to be significantly lower than Nonverbal IQ (NVIQ) scores. Full Scale IQ (FSIQ) scores did not reveal heterogeneity when gender was factored in. Age and type of abuse (with a moderate effect size) on the other hand, showed significant differences among groups. Statistical analyses of SB5 Factor Index Scores revealed that abused children, in general, have significantly higher Visual-Spatial Processing (VS) and Quantitative Reasoning (QR) scores and lower scores in Knowledge (KN). There was a large effect size found in such an analysis. Age (with a large effect size), gender and type of abuse (with moderate effect sizes) give significant variations to this obtained profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

Including granulometric sediment coastal data composition into the Black Sea GIS

NASA Astrophysics Data System (ADS)

Zhuk, Elena; Khaliulin, Alexey; Krylenko, Marina; Krylenko, Viacheslav; Zodiatis, George; Nikolaidis, Marios; Nikolaidis, Andreas

2017-09-01

The module structure of the Black Sea GIS allows the increasing of its functionality, including new data types and defining new procedures accessing them, their visualization and integration with existing data by their conjoint processing and representation. The Black Sea GIS is released as free software; Mapserver is used as a mapping service; MySQL DBMS works with relational data. A new additional feature provided, is the ability of including coastal data obtained in SB SIO RAS. The data represent granulometric composition of the Anapa bay-bar sediments. The Anapa bay-bar is an accumulative sand form (about 50 km long) located on the northwest Russian Black Sea coast. The entire bay-bar and especially its southern part with sand beaches 50-200 m wide is intensively used in recreation. This work is based on the results of field studies of 2010-2014 in the southern part of the Anapa bay-bar researched by scientists of the Shirshov Institute of Oceanology RAS. Since the shore under consideration has no clearly pronounced reference points, "virtual" points located within 1 km distance from each other were selected. Transversal profiles cross these points. The granulometric composition was studied along with 45 profiles. The samples taken in every profile were from the most characteristic morphological parts of the beach. In this study we used shoreline zone samples. Twenty one granule fractions (mm) were separated in the laboratory. The module which processes coastal data allows to select coastal data based on territory/region and granulometric sediment composition. Also, it allows to visualize coastal maps with user-selected features combined with other GIS data.

Formononetin-induced apoptosis by activation of Ras/p38 mitogen-activated protein kinase in estrogen receptor-positive human breast cancer cells.

PubMed

Chen, J; Sun, L

2012-12-01

Formononetin is one of the main active components of red clover plants, and considered as a phytoestrogen. Its pharmacological effects in vivo may be either estrogenic or anti-estrogenic, mainly depending upon the estrogen levels. Our recent studies suggested that formononetin inactivated IGF1/IGF1R-PI3K/Akt pathways and decreased cyclin D1 mRNA and protein expression in human breast cancer cells in vitro and in vivo. In the present study, we further investigated the molecular mechanisms involved in the induced apoptosis effect of formononetin on breast cancer cells. Our results suggested that formononetin inhibited the proliferation of ER-positive MCF-7 cells and T47D cells. In contrast, formononetin could not inhibit the cell of growth of ER-negative breast cancer cells such as MDA-MB-435 S cells. We further found that formononetin activated MAPK signaling pathway in a dose-dependent manner, which resulted in the increased ratio of Bax/Bcl-2, and induced apoptosis on MCF-7 cells. However, when MCF-7 cells were pretreated with p38MAPK inhibitor SB203580 before formononetin, apoptosis induced by formononetin was significantly attenuated. Thus, we conclude that the induced apoptosis effect of formononetin on human breast cancer cells were related to Ras-p38MAPK pathway. Considering that red clover plants are widely used clinically, our results provide the foundation for future development of formononetin for treatment of ER-positive breast cancer. © Georg Thieme Verlag KG Stuttgart · New York.

Casting a Wider Net: Rational Synthesis Design of Low-Dimensional Bulk Materials.

PubMed

Benavides, Katherine A; Oswald, Iain W H; Chan, Julia Y

2018-01-16

The discovery of novel magnetic and electronic properties in low-dimensional materials has led to the pursuit of hierarchical materials with specific substructures. Low-dimensional solids are highly anisotropic by nature and show promise in new quantum materials leading to exotic physical properties not realized in three-dimensional materials. We have the opportunity to extend our synthetic strategy of the flux-growth method to designing single crystalline low-dimensional materials in bulk. The goal of this Account is to highlight the synthesis and physical properties of several low-dimensional intermetallic compounds containing specific structural motifs that are linked to desirable magnetic and electrical properties. We turned our efforts toward intermetallic compounds consisting of antimony nets because they are closely linked to properties such as high carrier mobility (the velocity of an electron moving through a material under a magnetic field) and large magnetoresistance (the change in resistivity with an applied magnetic field), both of which are desirable properties for technological applications. The SmSb 2 structure type is of particular interest because it is comprised of rectangular antimony nets and rare earth ions stacked between the antimony nets in a square antiprismatic environment. LnSb 2 (Ln = La-Nd, Sm) have been shown to be highly anisotropic with SmSb 2 exhibiting magnetoresistance of over 50000% for H∥c axis and ∼2400% for H∥ab. Using this structure type as an initial building block, we envision the insertion of transition metal substructures into the SmSb 2 structure type to produce ternary materials. We describe compounds adopting the HfCuSi 2 structure type as an insertion of a tetrahedral transition metal-antimony subunit into the LnSb 2 host structure. We studied LnNi 1-x Sb 2 (Ln = Y, Gd-Er), where positive magnetoresistance reaching above 100% was found for the Y, Gd, and Ho analogues. We investigated the influence of the transition metal sublattice by substituting Ni into Ce(Cu 1-x Ni x ) y Sb 2 (y < 0.8) and found that the material is highly anisotropic and metamagnetic transitions appear at ∼0.5 and 1 T in compounds with higher Ni concentration. Metamagnetism is characterized by a sharp increase in the magnetic response of a material with increasing applied magnetic field, which was also observed in LnSb 2 (Ln = Ce-Nd). We also endeavored to study materials that possess a transition metal sublattice with the potential for geometric frustration. An example is the La 2 Fe 4 Sb 5 structure type, which consists of antimony square nets and an iron-based network arranged in nearly equilateral triangles, a feature found in magnetically frustrated systems. We discovered spin glass behavior in Ln 2 Fe 4 Sb 5 (Ln = La-Nd, Sm) and evidence that the transition metal sublattice contributes to the magnetic interactions of Ln 2 Fe 4 Sb 5 . We investigated the magnetic properties of Pr 2 Fe 4-x Co x Sb 5 (x < 2.3) and found that as the Co concentration increases, a second magnetic transition leads from a localized to an itinerant system. The La 2 Fe 4 Sb 5 structure type is quite robust and allows for the incorporation of other transition metals, thereby making it an excellent candidate to study competing magnetic interactions in lanthanide-containing intermetallic compounds. In this manuscript, we aim to share our experiences of bulk intermetallic compounds to inspire the development of new low-dimensional materials.

Overexpression of K-p21Ras play a prominent role in lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Peng-bo; Zhou, Xin-liang; Yang, Ju-lun

2018-06-01

The proto-oncogene ras product, p21Ras, has been found overexpression in many human tumors. However, the subtypes of overexpressed p21Ras still remain unclear. The purpose of this study was to investigate overexpressed isoforms of p21Ras and their roles in the progress of lung cancer. Method: The expression of total p21Ras in normal lung tissues and lung cancers was determined by immunohistochemically staining with monoclonal antibody (Mab) KGHR-1 which could recognize and broad spectrum reaction with the (K/H/N) ras protein. Then, the isoforms of p21Ras was examined by specific Mab for each p21Ras subtypes. Results: Low expression of total p21Ras was found in 26.67% (8/30) of normal lung tissues, and 81.31% (87/107) of adenocarcinoma harbored overexpressed total p21Ras. Besides, 70.00% (35/50) of squamous cell carcinoma were detected overexpressed total p21Ras. In addition, 122 lung cancer tissues from overexpression of total p21Ras protein were selected to detect the expression of each subtype. And all the 122 lung cancer tissues were K-p21Ras overexpression. Moreover, there was a statistical significance difference between the expression level of total p21Ras and differentiation, and the same results were observed between the expression level of total p21Ras and lymph node metastasis (P<0.05). However, there was no correlation between the expression level of total p21Ras and gender, age, tumor size (P>0.05). Conclusions: Overexpression of K-p21Ras plays a prominent role in the progress of lung cancer and it is suggested that the p21Ras could serve as a promising treatment target in lung cancer.

(Tl, Sb) and (Tl, Bi) binary surface reconstructions on Ge(111) substrate

NASA Astrophysics Data System (ADS)

Gruznev, D. V.; Bondarenko, L. V.; Tupchaya, A. Y.; Yakovlev, A. A.; Mihalyuk, A. N.; Zotov, A. V.; Saranin, A. A.

2018-03-01

2D compounds made of Group-III and Group-V elements on the surface of silicon and germanium attract considerable attention due to prospects of creating III-V binary monolayers, which are predicted to hold advanced physical properties. In the present work, we have investigated two such systems, (Tl, Sb)/Ge(111) and (Tl, Bi)/Ge(111) using scanning tunneling microscopy, low energy electron diffraction observations and density-functional-theory calculations. In addition to the previously reported surface structures of 2D (Tl, Sb) and (Tl, Bi) compounds on Si(111), we found new ones, namely, √{ 7} × √{ 7} and 3 × 3. Formation processes and plausible models of their atomic arrangements are discussed.

A comparative TCAD assessment of III-V channel materials for future high speed and low power logic applications

NASA Astrophysics Data System (ADS)

Gomes, U. P.; Takhar, K.; Ranjan, K.; Rathi, S.; Biswas, D.

2015-02-01

In this work, by means physics based drift-diffusion simulations, three different narrow band gap semiconductors; InAs, InSb and In0.53Ga0.47As, and their associated heterostructures have been studied for future high speed and low power logic applications. It is observed that In0.53Ga0.47As has higher immunity towards short channel effects with low DIBL and sub-threshold slope than InSb and InAs. Also it is observed that for the same device geometry InSb has the highest drive current and lower intrinsic delay but its ION/IOFF figure of merit is deteriorated due to excess leakage current.

Observation of Conductance Quantization in InSb Nanowire Networks

PubMed Central

2017-01-01

Majorana zero modes (MZMs) are prime candidates for robust topological quantum bits, holding a great promise for quantum computing. Semiconducting nanowires with strong spin orbit coupling offer a promising platform to harness one-dimensional electron transport for Majorana physics. Demonstrating the topological nature of MZMs relies on braiding, accomplished by moving MZMs around each other in a certain sequence. Most of the proposed Majorana braiding circuits require nanowire networks with minimal disorder. Here, the electronic transport across a junction between two merged InSb nanowires is studied to investigate how disordered these nanowire networks are. Conductance quantization plateaus are observed in most of the contact pairs of the epitaxial InSb nanowire networks: the hallmark of ballistic transport behavior. PMID:28665621

Preface

NASA Astrophysics Data System (ADS)

Pattison, Bryan; Borisov, Alexander

2017-06-01

The 19th International Symposium on Very High Energy Cosmic Ray Interactions (ISVHECRI 2016), held at the P.N. Lebedev Physical Institute of the Russian Academy of Sciences, Moscow (LPI RAS) from 22 to 28 August 2016, attracted more than 120 participants. The Symposium was carried out under the auspices of the International Union of Pure and Applied Physics (IUPAP) with financial support from the Federal Agency for Scientific Organizations and the Russian Foundation for Basic Research.

The effects of mothers’ musical background on sedentary behavior, physical activity, and exercise adherence in their 5-6-years-old children using movement-to-music video program

PubMed Central

Raitanen, Jani; Husu, Pauliina; Kujala, Urho M.; Luoto, Riitta M.

2018-01-01

Objectives The purpose of this study was to examine whether mothers’ musical background has an effect on their own and their children’s sedentary behavior (SB) and physical activity (PA). The aim was also to assess children’s and their mothers’ exercise adherence when using movement-to-music video program. Design Sub-group analysis of an intervention group in a randomized controlled trial (ISRCTN33885819). Method Seventy-one mother-child-pairs were divided into two categories based on mothers’ musical background. Each pair performed 8 weeks exercise intervention using movement-to-music video program. SB and PA were assessed objectively by accelerometer, and exercise activity, fidelity, and enjoyment were assessed via exercise diaries and questionnaires. Logistic regression model was used to analyze associations in the main outcomes between the groups. Results Those children whose mothers had musical background (MB) had greater probability to increase their light PA during the intervention, but not moderate-to-vigorous PA compared to those children whose mothers did not have musical background (NMB). SB increased in both groups. Mothers in the NMB group had greater probability to increase their light and moderate-to-vigorous PA and decrease their SB than mothers in the MB group. However, exercise adherence decreased considerably in all groups. Completeness, fidelity, and enjoyment were higher among the NMB group compared to the MB group. Conclusions The present results showed that mothers without musical background were more interested in movement-to-music exercises, as well as their children. For further studies it would be important to evaluate an effect of children’s own music-based activities on their SB and PA. PMID:29668726

Physical Therapy and Infants with Down's Syndrome: The Effects of Early Intervention.

ERIC Educational Resources Information Center

Harris, Susan R.

1981-01-01

The neuromotor development of Down's syndrome (DS) infants is reviewed, current physical therapy approaches are cited, a neurodevelopmental treatment (NDT) approach is described, and a study on the effects of NDT on motor performance in DS infants is reported. (SB)

Resistance of R-Ras knockout mice to skin tumour induction

PubMed Central

May, Ulrike; Prince, Stuart; Vähätupa, Maria; Laitinen, Anni M.; Nieminen, Katriina; Uusitalo-Järvinen, Hannele; Järvinen, Tero A. H.

2015-01-01

The R-ras gene encodes a small GTPase that is a member of the Ras family. Despite close sequence similarities, R-Ras is functionally distinct from the prototypic Ras proteins; no transformative activity and no activating mutations of R-Ras in human malignancies have been reported for it. R-Ras activity appears inhibitory towards tumour proliferation and invasion, and to promote cellular quiescence. Contrary to this, using mice with a deletion of the R-ras gene, we found that R-Ras facilitates DMBA/TPA-induced skin tumour induction. The tumours appeared in wild-type (WT) mice on average 6 weeks earlier than in R-Ras knockout (R-Ras KO) mice. WT mice developed almost 6 times more tumours than R-Ras KO mice. Despite strong R-Ras protein expression in the dermal blood vessels, no R-Ras could be detected in the epidermis from where the tumours arose. The DMBA/TPA skin tumourigenesis-model is highly dependent upon inflammation, and we found a greatly attenuated skin inflammatory response to DMBA/TPA-treatment in the R-Ras KO mice in the context of leukocyte infiltration and proinflammatory cytokine expression. Thus, these data suggest that despite its characterised role in promoting cellular quiescence, R-Ras is pro-tumourigenic in the DMBA/TPA tumour model and important for the inflammatory response to DMBA/TPA treatment. PMID:26133397

Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK

PubMed Central

Wang, Qin; Downey, Gregory P.; McCulloch, Christopher A.

2011-01-01

In connective tissue cells, IL-1-induced ERK activation leading to matrix metalloproteinase (MMP)-3 expression is dependent on cooperative interactions between focal adhesions and the endoplasmic reticulum (ER). As Ras can be activated on the ER, we investigated the role of Ras in IL-1 signaling and focal adhesion formation. We found that constitutively active H-Ras, K-Ras or N-Ras enhanced focal adhesion maturation and β1-integrin activation. IL-1 promoted the accumulation of Ras isoforms in ER and focal adhesion fractions, as shown in cells cotransfected with GFP-tagged Ras isoforms and YFP-ER protein and by analysis of subcellular fractions enriched for ER or focal adhesion proteins. Dominant-negative H-Ras or K-Ras reduced accumulation of H-Ras and K-Ras in focal adhesions induced by IL-1 and also blocked ERK activation and focal adhesion maturation. Ras-GRF was enriched constitutively in focal adhesion fractions and was required for Ras recruitment to focal adhesions. We conclude that Ras activation and IL-1 signaling are interactive processes that regulate the maturation of focal adhesions, which, in turn, is required for ERK activation.—Wang, Q., Downey, G. P., McCulloch, C. A. Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK. PMID:21719512

Targeting the RAS oncogene

PubMed Central

Takashima, Asami

2013-01-01

Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies. PMID:23360111

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

PubMed

Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

2010-06-30

Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

PubMed

Vercoulen, Yvonne; Kondo, Yasushi; Iwig, Jeffrey S; Janssen, Axel B; White, Katharine A; Amini, Mojtaba; Barber, Diane L; Kuriyan, John; Roose, Jeroen P

2017-09-27

RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1

PubMed Central

Iwig, Jeffrey S; Vercoulen, Yvonne; Das, Rahul; Barros, Tiago; Limnander, Andre; Che, Yan; Pelton, Jeffrey G; Wemmer, David E; Roose, Jeroen P; Kuriyan, John

2013-01-01

RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI: http://dx.doi.org/10.7554/eLife.00813.001 PMID:23908768

Importance of including ammonium sulfate ((NH4)2SO4) aerosols for ice cloud parameterization in GCMs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharjee, P. S.; Sud, Yogesh C.; Liu, Xiaohong

2010-02-22

A common deficiency of many cloud-physics parameterizations including the NASA’s microphysics of clouds with aerosol- cloud interactions (hereafter called McRAS-AC) is that they simulate less (larger) than the observed ice cloud particle number (size). A single column model (SCM) of McRAS-AC and Global Circulation Model (GCM) physics together with an adiabatic parcel model (APM) for ice-cloud nucleation (IN) of aerosols were used to systematically examine the influence of ammonium sulfate ((NH4)2SO4) aerosols, not included in the present formulations of McRAS-AC. Specifically, the influence of (NH4)2SO4 aerosols on the optical properties of both liquid and ice clouds were analyzed. First anmore » (NH4)2SO4 parameterization was included in the APM to assess its effect vis-à-vis that of the other aerosols. Subsequently, several evaluation tests were conducted over the ARM-SGP and thirteen other locations (sorted into pristine and polluted conditions) distributed over marine and continental sites with the SCM. The statistics of the simulated cloud climatology were evaluated against the available ground and satellite data. The results showed that inclusion of (NH4)2SO4 in the SCM made a remarkable improvement in the simulated effective radius of ice clouds. However, the corresponding ice-cloud optical thickness increased more than is observed. This can be caused by lack of cloud advection and evaporation. We argue that this deficiency can be mitigated by adjusting the other tunable parameters of McRAS-AC such as precipitation efficiency. Inclusion of ice cloud particle splintering introduced through well- established empirical equations is found to further improve the results. Preliminary tests show that these changes make a substantial improvement in simulating the cloud optical properties in the GCM, particularly by simulating a far more realistic cloud distribution over the ITCZ.« less

Antigastric parietal cell and antithyroid autoantibodies in patients with recurrent aphthous stomatitis.

PubMed

Wu, Yang-Che; Wu, Yu-Hsueh; Wang, Yi-Ping; Chang, Julia Yu-Fong; Chen, Hsin-Ming; Sun, Andy

2017-01-01

Anti-gastric parietal cell antibody (GPCA), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA) have not yet been reported in patients with recurrent aphthous stomatitis (RAS). This study mainly assessed the frequencies of the presence of serum GPCA, TGA, and TMA in different types of RAS patients. Serum GPCA, TGA, and TMA levels were measured in 355 RAS patients of different subtypes and in 355 age- and sex-matched healthy control individuals. We found that 13.0%, 19.4%, and 19.7% of 355 RAS patients, 16.7%, 23.3%, and 21.7% of 60 major-typed RAS patients, 12.2%, 18.6%, and 19.3% of 295 minor-typed RAS patients, 18.1%, 20.0%, and 21.9% of 160 atrophic glossitis-positive RAS (AG+/RAS) patients, and 8.7%, 19.0%, and 17.9% of 195 AG-negative RAS (AG-/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. RAS, major-typed RAS, minor-typed RAS, AG+/RAS, and AG-/RAS patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control individuals (all p < 0.001). Of 65 TGA/TMA-positive RAS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 76.9%, 12.3%, and 10.8% of these TGA/TMA-positive RAS patients had normal, lower, and higher serum TSH levels, respectively. We conclude that approximately one-third RAS patients may have GPCA/TGA/TMA positivity in their sera. Because some GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and some TGA/TMA-positive patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these patients should be referred to doctors for further management. Copyright © 2016. Published by Elsevier B.V.

Ras and relatives--job sharing and networking keep an old family together.

PubMed

Ehrhardt, Annette; Ehrhardt, Götz R A; Guo, Xuecui; Schrader, John W

2002-10-01

Many members of the Ras superfamily of GTPases have been implicated in the regulation of hematopoietic cells, with roles in growth, survival, differentiation, cytokine production, chemotaxis, vesicle-trafficking, and phagocytosis. The well-known p21 Ras proteins H-Ras, N-Ras, K-Ras 4A, and K-Ras 4B are also frequently mutated in human cancer and leukemia. Besides the four p21 Ras proteins, the Ras subfamily of the Ras superfamily includes R-Ras, TC21 (R-Ras2), M-Ras (R-Ras3), Rap1A, Rap1B, Rap2A, Rap2B, RalA, and RalB. They exhibit remarkable overall amino acid identities, especially in the regions interacting with the guanine nucleotide exchange factors that catalyze their activation. In addition, there is considerable sharing of various downstream effectors through which they transmit signals and of GTPase activating proteins that downregulate their activity, resulting in overlap in their regulation and effector function. Relatively little is known about the physiological functions of individual Ras family members, although the presence of well-conserved orthologs in Caenorhabditis elegans suggests that their individual roles are both specific and vital. The structural and functional similarities have meant that commonly used research tools fail to discriminate between the different family members, and functions previously attributed to one family member may be shared with other members of the Ras family. Here we discuss similarities and differences in activation, effector usage, and functions of different members of the Ras subfamily. We also review the possibility that the differential localization of Ras proteins in different parts of the cell membrane may govern their responses to activation of cell surface receptors.

Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3.

PubMed

Czikora, Agnes; Kedei, Noemi; Kalish, Heather; Blumberg, Peter M

2017-12-01

RasGRP comprises a family of guanine nucleotide exchange factors, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP1 possesses REM (Ras exchange), GEF (catalytic), EF-hand, C1, SuPT (suppressor of PT), and PT (plasma membrane-targeting) domains, among which the C1 domain drives membrane localization in response to diacylglycerol or phorbol ester and the PT domain recognizes phosphoinositides. The homologous family member RasGRP3 shows less plasma membrane localization. The objective of this study was to explore the role of the different domains of RasGRP3 in membrane translocation in response to phorbol esters. The full-length RasGRP3 shows limited translocation to the plasma membrane in response to PMA, even when the basic hydrophobic cluster in the PT domain, reported to be critical for RasGRP1 translocation to endogenous activators, is mutated to resemble that of RasGRP1. Moreover, exchange of the C-termini (SuPT-PT domain) of the two proteins had little effect on their plasma membrane translocation. On the other hand, while the C1 domain of RasGRP3 alone showed partial plasma membrane translocation, truncated RasGRP3 constructs, which contain the PT domain and are missing the REM, showed stronger translocation, indicating that the REM of RasGRP3 was a suppressor of its membrane interaction. The REM of RasGRP1 failed to show comparable suppression of RasGRP3 translocation. The marked differences between RasGRP3 and RasGRP1 in membrane interaction necessarily will contribute to their different behavior in cells and are relevant to the design of selective ligands as potential therapeutic agents. Published by Elsevier B.V.

Developing a community based service model for disability: Listening to the needs of all beneficiaries and providers.

PubMed

Collins, Katrina

2017-12-11

To inform the strategic and operational development of a community based service model at the Crann Centre, Cork, Ireland for SB children, adults, their families and providers. A needs assessment was conducted by gathering the views of multiple stakeholder perspectives within the SB community in the geographical region the Centre will serve. The intention is to create project deliverables that are responsive to the needs highlighted through this research. The study used a multi method design with a participatory research approach to explore the needs of SB individuals, families and providers. This involved in depth interviews, focus groups and online surveys. One hundred and fifty-nine respondents contributed to this qualitative needs assessment. The research established a range of psychosocial, clinical, vocational and educational issues causing ongoing difficulties for SB individuals and families. Providers highlighted supports that would benefit the social and clinical wellbeing of persons with SB. Collectively participants in the study reported that there was an absence of coordinated, continuous and comprehensive service delivery for the SB community in the region. This was amplified by geographical location of services and access to relevant supports. Consensus across stakeholders in this research pointed to the necessity for an innovative model of community based provision at the Crann Centre. This was described as offering a service with family at the core of an assets based model of practice. A key finding was the lack of importance placed on the social and emotional development of SB individuals. Traditionally participants described a singular focus on physical health through clinically defined treatment models. The desire for a social model of disability that informed health and wellbeing of SB individuals and families emerged as a prominent recommendation from the research.

A cross-sectional study examining the expression of splice variants K-RAS4A and K-RAS4B in advanced non-small-cell lung cancer patients.

PubMed

Aran, Veronica; Masson Domingues, Pedro; Carvalho de Macedo, Fabiane; Moreira de Sousa, Carlos Augusto; Caldas Montella, Tatiane; de Souza Accioly, Maria Theresa; Ferreira, Carlos Gil

2018-02-01

Mammalian cells differently express 4 RAS isoforms: H-RAS, N-RAS, K-RAS4A and K-RAS4B, which are important in promoting oncogenic processes when mutated. In lung cancer, the K-RAS isoform is the most frequently altered RAS protein, being also a difficult therapeutic target. Interestingly, there are two K-RAS splice variants (K-RAS4A and K-RAS4B) and little is known about the role of K-RAS4A. Most studies targeting K-RAS, or analysing it as a prognostic factor, have not taken into account the two isoforms. Consequently, the in-depth investigation of them is needed. The present study analysed 98 specimens from advanced non-small cell lung cancer (NSCLC) adenocarcinoma patients originated from Brazil. The alterations present in K-RAS at the DNA level (Sanger sequencing) as well as the expression of the splicing isoforms at the RNA (qRT-PCR) and protein levels (immunohistochemistry analysis), were evaluated. Possible associations between clinicopathological features and the molecular findings were also investigated. Our results showed that in the non-smoking population, the cancer incidence was higher among women. In contrast, in smokers and former smokers, the incidence was higher among men. Regarding sequencing results, 10.5% of valid samples presented mutations in exon 2, being all wild-type for exon 3, and the most frequently occurring base change was the transversion G → T. Our qRT-PCR and immunohistochemical analysis showed that both, K-RAS4A and K-RAS4B, were differently expressed in NSCLC tumour samples. For example, tumour specimens showed higher K-RAS4A mRNA expression in relation to commercial normal lung control than did K-RAS4B. In addition, K-RAS4B protein expression was frequently stronger than K-RAS4A in the patients analysed. Our results highlight the differential expression of K-RAS4A and K-RAS4B in advanced adenocarcinoma NSCLC patients and underline the need to further clarify the enigma behind their biological significance in various cancer types, including NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

Downregulation of Ras C-terminal processing by JNK inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mouri, Wataru; Department of Neurosurgery, Yamagata University School of Medicine, Yamagata 990-9585; Biology Division, National Cancer Center Research Institute, Tokyo 104-0045

2008-06-27

After translation, Ras proteins undergo a series of modifications at their C-termini. This post-translational C-terminal processing is essential for Ras to become functional, but it remains unknown whether and how Ras C-terminal processing is regulated. Here we show that the C-terminal processing and subsequent plasma membrane localization of H-Ras as well as the activation of the downstream signaling pathways by H-Ras are prevented by JNK inhibition. Conversely, JNK activation by ultraviolet irradiation resulted in promotion of C-terminal processing of H-Ras. Furthermore, increased cell density promoted C-terminal processing of H-Ras most likely through an autocrine/paracrine mechanism, which was also blocked undermore » JNK-inhibited condition. Ras C-terminal processing was sensitive to JNK inhibition in the case of H- and N-Ras but not K-Ras, and in a variety of cell types. Thus, our results suggest for the first time that Ras C-terminal processing is a regulated mechanism in which JNK is involved.« less

Mid-infrared emission and Judd-Ofelt analysis of Dy3+-doped infrared Ga-Sb-S and Ga-Sb-S-PbI2 chalcohalide glasses

NASA Astrophysics Data System (ADS)

Guo, Jixiao; Jiao, Qing; He, Xiaolong; Guo, Hansong; Tong, Jianghao; Zhang, Zhihang; Jiang, Fuchao; Wang, Guoxiang

2018-03-01

Dy3+-doped Ga-Sb-S and Ga-Sb-S-PbI2 chalcohalide glasses were prepared by traditional melt quenching method. The effect of halide PbI2 on the physical and optical properties of Dy3+ ions was investigated. The density and ionic concentration of the host sample increased with the introduction of PbI2 halides, whereas the refractive index at 1.55 μm decreased. The Judd-Ofelt parameters showed that Ω2 increased in PbI2-modified glass, whereas the Ω6 value showed the opposite tendency. Infrared emission spectrum also showed that the intensity increased with PbI2 addition, and considerable enhancement at 2.8 μm was observed in the mid-infrared region. The halide PbI2 promoted the reduction of phonon energy of the host and the improvement of the laser pump efficiency, which led to the construction of optimized infrared glass materials for optical applications.

Synthetic Studies of Antimony Sulfur Iodide and Predictions/Synthesis of New Nitrogen Containing Crystal Structures.

DTIC Science & Technology

1983-02-01

Okazaki, 2 it appeared likely that well-aligned SbSI would have extremely useful piezoelectric properties. It was appreciated that a source of high purity...which often facilitate this, and may also lead to special physical effects (as with the ferroelectric behavior of SbSI). In hydroxyapatite , there are two...Fabrication of Piezoelectric Cerdmics," Ferroelectrics 41, 77-69 (1982). 3. P.E.O. Morgan, "Synthetic Studies of Antimony Sulfur Iodide," Proposal to ONR from

Electrical, Optical and Structural Studies of INAS/INGASB VLWIR Superlattices

DTIC Science & Technology

2013-01-01

period measured by x-ray diffraction and the optical band gap energy determined by the photoresponse spectra. Sample InAs (Å) GaSb (Å) In (%) IF (Å...8x8 EFA. 22 Temperature-dependent lattice constants, band gap energies , and other physical data for InAs and GaSb are taken from Vurgaftman et al...gallium antimonide to achieve energy band gaps less than 50 meV with a superlattice period on the order of 68 Å. Similar to the work reported on

Review: Intracardiac intracellular angiotensin system in diabetes

PubMed Central

Kumar, Rajesh; Yong, Qian Chen; Thomas, Candice M.

2012-01-01

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies. PMID:22170614

The influence of lightning activity and anthropogenic factors on large-scale characteristics of natural fires

NASA Astrophysics Data System (ADS)

Eliseev, A. V.; Mokhov, I. I.; Chernokulsky, A. V.

2017-01-01

A module for simulating of natural fires (NFs) in the climate model of the A.M. Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences (IAP RAS CM), is extended with respect to the influence of lightning activity and population density on the ignition frequency and fire suppression. The IAP RAS CM is used to perform numerical experiments in accordance with the conditions of the project that intercompares climate models, CMIP5 (Coupled Models Intercomparison Project, phase 5). The frequency of lightning flashes was assigned in accordance with the LIS/OTD satellite data. In the calculations performed, anthropogenic ignitions play an important role in NF occurrences, except for regions at subpolar latitudes and, to a lesser degree, tropical and subtropical regions. Taking into account the dependence of fire frequency on lightning activity and population density intensifies the influence of characteristics of natural fires on the climate changes in tropics and subtropics as compared to the version of the IAP RAS CM that does not take the influence of ignition sources on the large-scale characteristics of NFs into consideration.

RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation

PubMed Central

Lim, Chinten James; Spiegelman, George B.; Weeks, Gerald

2001-01-01

Disruption of Dictyostelium rasC, encoding a Ras subfamily protein, generated cells incapable of aggregation. While rasC expression is enriched in a cell type-specific manner during post-aggregative development, the defect in rasC– cells is restricted to aggregation and fully corrected by application of exogenous cAMP pulses. cAMP is not produced in rasC– cells stimulated by 2′-deoxy-cAMP, but is produced in response to GTPγS in cell lysates, indicating that G-protein-coupled cAMP receptor activation of adenylyl cyclase is regulated by RasC. However, cAMP-induced ERK2 phosphorylation is unaffected in rasC– cells, indicating that RasC is not an upstream activator of the mitogen-activated protein kinase required for cAMP relay. rasC– cells also exhibit reduced chemotaxis to cAMP during early development and delayed response to periodic cAMP stimuli produced by wild-type cells in chimeric mixtures. Furthermore, cAMP-induced Akt/PKB phosphorylation through a phosphatidylinositide 3-kinase (PI3K)-dependent pathway is dramatically reduced in rasC– cells, suggesting that G-protein-coupled serpentine receptor activation of PI3K is regulated by RasC. Cells lacking the RasGEF, AleA, exhibit similar defects as rasC– cells, suggesting that AleA may activate RasC. PMID:11500376

RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation.

PubMed

Lim, C J; Spiegelman, G B; Weeks, G

2001-08-15

Disruption of Dictyostelium rasC, encoding a Ras subfamily protein, generated cells incapable of aggregation. While rasC expression is enriched in a cell type-specific manner during post-aggregative development, the defect in rasC(-) cells is restricted to aggregation and fully corrected by application of exogenous cAMP pulses. cAMP is not produced in rasC(-) cells stimulated by 2'-deoxy-cAMP, but is produced in response to GTPgammaS in cell lysates, indicating that G-protein-coupled cAMP receptor activation of adenylyl cyclase is regulated by RasC. However, cAMP-induced ERK2 phosphorylation is unaffected in rasC(-) cells, indicating that RasC is not an upstream activator of the mitogen-activated protein kinase required for cAMP relay. rasC(-) cells also exhibit reduced chemotaxis to cAMP during early development and delayed response to periodic cAMP stimuli produced by wild-type cells in chimeric mixtures. Furthermore, cAMP-induced Akt/PKB phosphorylation through a phosphatidylinositide 3-kinase (PI3K)-dependent pathway is dramatically reduced in rasC(-) cells, suggesting that G-protein-coupled serpentine receptor activation of PI3K is regulated by RasC. Cells lacking the RasGEF, AleA, exhibit similar defects as rasC(-) cells, suggesting that AleA may activate RasC.

Deconstructing Ras Signaling in the Thymus

PubMed Central

Kortum, Robert L.; Sommers, Connie L.; Pinski, John M.; Alexander, Clayton P.; Merrill, Robert K.; Li, Wenmei; Love, Paul E.

2012-01-01

Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1 deletion was required to block negative selection. This functional redundancy in RasGEFs during negative selection may act as a failsafe mechanism ensuring appropriate central tolerance. PMID:22586275

H-Ras Exerts Opposing Effects on Type I Interferon Responses Depending on Its Activation Status.

PubMed

Chen, Guann-An; Lin, Yun-Ru; Chung, Hai-Ting; Hwang, Lih-Hwa

2017-01-01

Using shRNA high-throughput screening, we identified H-Ras as a regulator of antiviral activity, whose depletion could enhance Sindbis virus replication. Further analyses indicated that depletion of H-Ras results in a robust increase in vesicular stomatitis virus infection and a decrease in Sendai virus (SeV)-induced retinoic acid-inducible gene-I-like receptor (RLR) signaling. Interestingly, however, ectopic expression of wild-type H-Ras results in a biphasic mode of RLR signaling regulation: while low-level expression of H-Ras enhances SeV-induced RLR signaling, high-level expression of H-Ras significantly inhibits this signaling. The inhibitory effects correlate with the activation status of H-Ras. As a result, oncogenic H-Ras, H-RasV12, strongly inhibits SeV-induced IFN-β promoter activity and type I interferon signaling. Conversely, the positive effects exerted by H-Ras on RLR signaling are independent of its signaling activity, as a constitutively inactive form of H-Ras, H-RasN17, also positively regulates RLR signaling. Mechanistically, we demonstrate that depletion of H-Ras reduces the formation of MAVS-TNF receptor-associated factor 3 signaling complexes. These results reveal that the H-Ras protein plays a role in promoting MAVS signalosome assembly in the mitochondria, whereas oncogenic H-Ras exerts a negative effect on type I IFN responses.

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

PubMed Central

Vidal, J; Muinelo, L; Dalmases, A; Jones, F; Edelstein, D; Iglesias, M; Orrillo, M; Abalo, A; Rodríguez, C; Brozos, E; Vidal, Y; Candamio, S; Vázquez, F; Ruiz, J; Guix, M; Visa, L; Sikri, V; Albanell, J; Bellosillo, B; López, R; Montagut, C

2017-01-01

Abstract Background RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments. PMID:28419195

Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling | Office of Cancer Genomics

Cancer.gov

In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras.

Aerothermodynamics of expert ballistic vehicle at hypersonic speeds

NASA Astrophysics Data System (ADS)

Kharitonov, A. M.; Adamov, N. P.; Chirkashenko, V. F.; Mazhul, I. I.; Shpak, S. I.; Shiplyuk, A. N.; Vasenyov, L. G.; Zvegintsev, V. I.; Muylaert, J. M.

2012-01-01

The European EXPErimental Re-entry Test bed (EXPERT) vehicle is intended for studying various basic phenomena, such as the boundary-layer transition on blunted bodies, real gas effects during shock wave/boundary layer interaction, and effect of surface catalycity. Another task is to develop methods for recalculating the results of windtunnel experiments to flight conditions. The EXPERT program implies large-scale preflight research, in particular, various calculations with the use of advanced numerical methods, experimental studies of the models in various wind tunnels, and comparative analysis of data obtained for possible extrapolation of data to in-flight conditions. The experimental studies are performed in various aerodynamic centers of Europe and Russia under contracts with ESA-ESTEC. In particular, extensive experiments are performed at the Von Karman Institute for Fluid Dynamics (VKI, Belgium) and also at the DLR aerospace center in Germany. At ITAM SB RAS, the experimental studies of the EXPERT model characteristic were performed under ISTC Projects 2109, 3151, and 3550, in the T-313 supersonic wind tunnel and AT-303 hypersonic wind tunnel.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

PubMed Central

2010-01-01

Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors. PMID:20591134

Relationship between sedentary behavior and depression: A mediation analysis of influential factors across the lifespan among 42,469 people in low- and middle-income countries.

PubMed

Stubbs, Brendon; Vancampfort, Davy; Firth, Joseph; Schuch, Felipe B; Hallgren, Mats; Smith, Lee; Gardner, Benjamin; Kahl, Kai G; Veronese, Nicola; Solmi, Marco; Carvalho, André F; Koyanagi, Ai

2018-03-15

Sedentary behavior (SB) is associated with diabetes, cardiovascular disease and low mood. There is a paucity of multi-national research investigating SB and depression, particularly among low- and middle-income countries. This study investigated the association between SB and depression, and factors which influence this. Cross-sectional data were analyzed from the World Health Organization's Study on Global Ageing and Adult Health. Depression was based on the Composite International Diagnostic Interview. The association between depression and SB (self-report) was estimated by multivariable linear and logistic regression analyses. Mediation analysis was used to identify influential factors. A total of 42,469 individuals (50.1% female, mean 43.8 years) were included. People with depression spent 25.6 (95%CI8.5-42.7) more daily minutes in SB than non-depressed participants. This discrepancy was most notable in adults aged ≥ 65y (35.6min more in those with depression). Overall, adjusting for socio-demographics and country, depression was associated with a 1.94 (95%CI1.31-2.85) times higher odds for high SB (i.e., ≥ 8h/day). The largest proportion of the SB-depression relationship was explained by mobility limitations (49.9%), followed by impairments in sleep/energy (43.4%), pain/discomfort (31.1%), anxiety (30.0%), disability (25.6%), cognition (16.1%), and problems with vision (11.0%). Other health behaviors (physical activity, alcohol consumption, smoking), body mass index, and social cohesion did not influence the SB-depression relationship. People with depression are at increased risk of engaging in high levels of SB. This first multi-national study offers potentially valuable insight for a number of hypotheses which may influence this relationship, although testing with longitudinal studies is needed. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

PubMed Central

Cox, Adrienne D.; Der, Channing J.; Philips, Mark R.

2015-01-01

RAS proteins require membrane association for their biological activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTIs) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anti-cancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated post-translational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. PMID:25878363

Moving to business - changes in physical activity and sedentary behavior after multilevel intervention in small and medium-size workplaces.

PubMed

Aittasalo, Minna; Livson, Matleena; Lusa, Sirpa; Romo, Ahti; Vähä-Ypyä, Henri; Tokola, Kari; Sievänen, Harri; Mänttäri, Ari; Vasankari, Tommi

2017-04-17

Regular physical activity (PA) promotes and excessive sedentary behavior (SB) deteriorates health. Yet the Finnish working-aged population spends most of the day sitting. A 1-year Moving To Business (MTB) -intervention supported small and medium-size workplaces to combat sedentariness. This paper reports the changes in employees' PA and SB from before MTB (baseline) to 1 year after baseline (follow-up). Twelve workplaces with a total of 396 employees participated. Each workplace nominated a team to promote PA and reduce SB at organizational, working unit and employee level. The teams were mentored regionally through meetings, workshop and tools. Changes in PA and SB were assessed with a questionnaire and an accelerometer. Wald Confidence Interval (Cl) for a difference of proportions with matched pairs was used in the questionnaire data (%-points with 95% CI) and linear mixed model in the accelerometer data (minutes and % of wear-time with 95% CI). The mean age of the respondents to the questionnaire (N = 296; 75%) was 42.6 (SD 10.9), 64% were women, 95% had some education after high school, 74% worked in the day shift, 71% did sedentary work and 51% were overweight. The mean number of actions implemented in the workplaces was 6.8 and the multilevel approach was fully applied in 6 workplaces. Based on the questionnaire the time spent in SB decreased from baseline to follow-up 16% (95% CI -29 to -3) in total and 22% (-41 to -3) at work. The accelerometer showed daily increases of 33.7 min (15.3 to 52.1) and 6.8% (3.1 to 10.4) in total PA, 30.9 min (15.3 to 46.5) and 6.1% (2.9 to 9.2) in light PA and 673 (209 to 1139) more steps at work. Daily SB at work decreased 44.9 min (-68.0 to -21.8) and 7.6% (-11.9 to -3.2). Daily leisure PA declined 11.0 min (-24.9 to 2.9) and 3.2% (-6.2 to -0.2). Number of levels or actions had no effect on changes. Employees' PA increased and SB reduced at work during the intervention. At the same time leisure PA decreased slightly. Workplaces can achieve meaningful changes in employees' PA and SB if assisted systematically. Controlled studies are needed to confirm the present findings. NCT01999205 , registration date 11/01/2013.

AMPK and Endothelial Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2

PubMed Central

Cho, Kwang-jin; Casteel, Darren E.; Prakash, Priyanka; Tan, Lingxiao; van der Hoeven, Dharini; Salim, Angela A.; Kim, Choel; Capon, Robert J.; Lacey, Ernest; Cunha, Shane R.; Gorfe, Alemayehu A.

2016-01-01

K-Ras must localize to the plasma membrane and be arrayed in nanoclusters for biological activity. We show here that K-Ras is a substrate for cyclic GMP-dependent protein kinases (PKGs). In intact cells, activated PKG2 selectively colocalizes with K-Ras on the plasma membrane and phosphorylates K-Ras at Ser181 in the C-terminal polybasic domain. K-Ras phosphorylation by PKG2 is triggered by activation of AMP-activated protein kinase (AMPK) and requires endothelial nitric oxide synthase and soluble guanylyl cyclase. Phosphorylated K-Ras reorganizes into distinct nanoclusters that retune the signal output. Phosphorylation acutely enhances K-Ras plasma membrane affinity, but phosphorylated K-Ras is progressively lost from the plasma membrane via endocytic recycling. Concordantly, chronic pharmacological activation of AMPK → PKG2 signaling with mitochondrial inhibitors, nitric oxide, or sildenafil inhibits proliferation of K-Ras-positive non-small cell lung cancer cells. The study shows that K-Ras is a target of a metabolic stress-signaling pathway that can be leveraged to inhibit oncogenic K-Ras function. PMID:27697864

Prepatellar and olecranon bursitis: literature review and development of a treatment algorithm.

PubMed

Baumbach, Sebastian F; Lobo, Christopher M; Badyine, Ilias; Mutschler, Wolf; Kanz, Karl-Georg

2014-03-01

Olecranon bursitis and prepatellar bursitis are common entities, with a minimum annual incidence of 10/100,000, predominantly affecting male patients (80 %) aged 40-60 years. Approximately 1/3 of cases are septic (SB) and 2/3 of cases are non-septic (NSB), with substantial variations in treatment regimens internationally. The aim of the study was the development of a literature review-based treatment algorithm for prepatellar and olecranon bursitis. Following a systematic review of Pubmed, the Cochrane Library, textbooks of emergency medicine and surgery, and a manual reference search, 52 relevant papers were identified. The initial differentiation between SB and NSB was based on clinical presentation, bursal aspirate, and blood sampling analysis. Physical findings suggesting SB were fever >37.8 °C, prebursal temperature difference greater 2.2 °C, and skin lesions. Relevant findings for bursal aspirate were purulent aspirate, fluid-to-serum glucose ratio <50 %, white cell count >3,000 cells/μl, polymorphonuclear cells >50 %, positive Gram staining, and positive culture. General treatment measures for SB and NSB consist of bursal aspiration, NSAIDs, and PRICE. For patients with confirmed NSB and high athletic or occupational demands, intrabursal steroid injection may be performed. In the case of SB, antibiotic therapy should be initiated. Surgical treatment, i.e., incision, drainage, or bursectomy, should be restricted to severe, refractory, or chronic/recurrent cases. The available evidence did not support the central European concept of immediate bursectomy in cases of SB. A conservative treatment regimen should be pursued, following bursal aspirate-based differentiation between SB and NSB.

In TCR-Stimulated T-cells, N-ras Regulates Specific Genes and Signal Transduction Pathways

PubMed Central

Lynch, Stephen J.; Zavadil, Jiri; Pellicer, Angel

2013-01-01

It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level T-cell receptor stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome. First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells. We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level T-cell receptor stimulus. Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments (Dntt, Slc9a6, Chst1, and Lars2). Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types. PMID:23755101

Case Report: Rhabdomyolysis in Service Member Following SERE Physical Training

DTIC Science & Technology

2017-09-19

Member following SERE physical training. Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Capt Matthew A Pombo Se. TASK...NOTES 14. ABSTRACT Case Report: Rhabdomyolysis in Service Member following SERE physical training. Authors: Matthew A. Pombo, DO (Capt, USAF...in Service Member following SERE physical training. Authors: Matthew A. Pombo, DO (Capt, USAF); Dwaipayan Chakraborti, MD (MAJ, USA); Joseph Marcus

Ras GTPases Modulate Morphogenesis, Sporulation and Cellulase Gene Expression in the Cellulolytic Fungus Trichoderma reesei

PubMed Central

Zhang, Jiwei; Zhang, Yanmei; Zhong, Yaohua; Qu, Yinbo; Wang, Tianhong

2012-01-01

Background The model cellulolytic fungus Trichoderma reesei (teleomorph Hypocrea jecorina) is capable of responding to environmental cues to compete for nutrients in its natural saprophytic habitat despite its genome encodes fewer degradative enzymes. Efficient signalling pathways in perception and interpretation of environmental signals are indispensable in this process. Ras GTPases represent a kind of critical signal proteins involved in signal transduction and regulation of gene expression. In T. reesei the genome contains two Ras subfamily small GTPases TrRas1 and TrRas2 homologous to Ras1 and Ras2 from S. cerevisiae, but their functions remain unknown. Methodology/Principal Findings Here, we have investigated the roles of GTPases TrRas1 and TrRas2 during fungal morphogenesis and cellulase gene expression. We show that both TrRas1 and TrRas2 play important roles in some cellular processes such as polarized apical growth, hyphal branch formation, sporulation and cAMP level adjustment, while TrRas1 is more dominant in these processes. Strikingly, we find that TrRas2 is involved in modulation of cellulase gene expression. Deletion of TrRas2 results in considerably decreased transcription of cellulolytic genes upon growth on cellulose. Although the strain carrying a constitutively activated TrRas2G16V allele exhibits increased cellulase gene transcription, the cbh1 and cbh2 expression in this mutant still strictly depends on cellulose, indicating TrRas2 does not directly mediate the transmission of the cellulose signal. In addition, our data suggest that the effect of TrRas2 on cellulase gene is exerted through regulation of transcript abundance of cellulase transcription factors such as Xyr1, but the influence is independent of cAMP signalling pathway. Conclusions/Significance Together, these findings elucidate the functions for Ras signalling of T. reesei in cellular morphogenesis, especially in cellulase gene expression, which contribute to deciphering the powerful competitive ability of plant cell wall degrading fungi in nature. PMID:23152805

Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering

PubMed Central

Blaževitš, Olga; Mideksa, Yonatan G.; Šolman, Maja; Ligabue, Alessio; Ariotti, Nicholas; Nakhaeizadeh, Hossein; Fansa, Eyad K.; Papageorgiou, Anastassios C.; Wittinghofer, Alfred; Ahmadian, Mohammad R.; Abankwa, Daniel

2016-01-01

Galectin-1 (Gal-1) dimers crosslink carbohydrates on cell surface receptors. Carbohydrate-derived inhibitors have been developed for cancer treatment. Intracellularly, Gal-1 was suggested to interact with the farnesylated C-terminus of Ras thus specifically stabilizing GTP-H-ras nanoscale signalling hubs in the membrane, termed nanoclusters. The latter activity may present an alternative mechanism for how overexpressed Gal-1 stimulates tumourigenesis. Here we revise the current model for the interaction of Gal-1 with H-ras. We show that it indirectly forms a complex with GTP-H-ras via a high-affinity interaction with the Ras binding domain (RBD) of Ras effectors. A computationally generated model of the Gal-1/C-Raf-RBD complex is validated by mutational analysis. Both cellular FRET as well as proximity ligation assay experiments confirm interaction of Gal-1 with Raf proteins in mammalian cells. Consistently, interference with H-rasG12V-effector interactions basically abolishes H-ras nanoclustering. In addition, an intact dimer interface of Gal-1 is required for it to positively regulate H-rasG12V nanoclustering, but negatively K-rasG12V nanoclustering. Our findings suggest stacked dimers of H-ras, Raf and Gal-1 as building blocks of GTP-H-ras-nanocluster at high Gal-1 levels. Based on our results the Gal-1/effector interface represents a potential drug target site in diseases with aberrant Ras signalling. PMID:27087647

Metabolic Rate Regulation by the Renin-Angiotensin System: Brain vs. Body

PubMed Central

Grobe, Justin L.; Rahmouni, Kamal; Liu, Xuebo; Sigmund, Curt D.

2013-01-01

Substantial evidence supports a role for the renin-angiotensin system (RAS) in the regulation of metabolic function, but an apparent paradox exists where genetic or pharmacological inhibition of the RAS occasionally have similar physiological effects as chronic angiotensin infusion. Similarly, while RAS targeting in animal models has robust metabolic consequences, effects in humans are more subtle. Here we review the data supporting a role for the RAS in metabolic rate regulation and propose a model where the local brain RAS works in opposition to the peripheral RAS, thus helping to explain the paradoxically similar effects of RAS supplementation and inhibition. Selectively modulating the peripheral RAS or brain RAS may thus provide a more effective treatment paradigm for obesity and obesity-related disorders. PMID:22491893

The Affordable Medicines Facility-malaria (AMFm): are remote areas benefiting from the intervention?

PubMed

Ye, Yazoume; Arnold, Fred; Noor, Abdisalan; Wamukoya, Marilyn; Amuasi, John; Blay, Samuel; Mberu, Blessing; Ren, Ruilin; Kyobutungi, Catherine; Wekesah, Frederick; Gatakaa, Hellen; Toda, Mitsuru; Njogu, Julius; Evance, Illah; O'Connell, Kathryn; Shewchuk, Tanya; Thougher, Sarah; Mann, Andrea; Willey, Barbara; Goodman, Catherine; Hanson, Kara

2015-10-09

To assess the availability, price and market share of quality-assured artemisinin-based combination therapy (QAACT) in remote areas (RAs) compared with non-remote areas (nRAs) in Kenya and Ghana at end-line of the Affordable Medicines Facility-malaria (AMFm) intervention. Areas were classified by remoteness using a composite index computed from estimated travel times to three levels of service centres. The index was used to five categories of remoteness, which were then grouped into two categories of remote and non-remote areas. The number of public or private outlets with the potential to sell or distribute anti-malarial medicines, screened in nRAs and RAs, respectively, was 501 and 194 in Ghana and 9980 and 2353 in Kenya. The analysis compares RAs with nRAs in terms of availability, price and market share of QAACT in each country. QAACT were similarly available in RAs as nRAs in Ghana and Kenya. In both countries, there was no statistical difference in availability of QAACT with AMFm logo between RAs and nRAs in public health facilities (PHFs), while private-for-profit (PFP) outlets had lower availability in RA than in nRAs (Ghana: 66.0 vs 82.2 %, p < 0.0001; Kenya: 44.9 vs 63.5 %, p = <0.0001. The median price of QAACT with AMFm logo for PFP outlets in RAs (USD1.25 in Ghana and USD0.69 in Kenya) was above the recommended retail price in Ghana (US$0.95) and Kenya (US$0.46), and much higher than in nRAs for both countries. QAACT with AMFm logo represented the majority of QAACT in RAs and nRAs in Kenya and Ghana. In the PFP sector in Ghana, the market share for QAACT with AMFm logo was significantly higher in RAs than in nRAs (75.6 vs 51.4 %, p < 0.0001). In contrast, in similar outlets in Kenya, the market share of QAACT with AMFm logo was significantly lower in RAs than in nRAs (39.4 vs 65.1 %, p < 0.0001). The findings indicate the AMFm programme contributed to making QAACT more available in RAs in these two countries. Therefore, the AMFm approach can inform other health interventions aiming at reaching hard-to-reach populations, particularly in the context of universal access to health interventions. However, further examination of the factors accounting for the deep penetration of the AMFm programme into RAs is needed to inform actions to improve the healthcare delivery system, particularly in RAs.

Phenotypic Screening Identifies Protein Synthesis Inhibitors as H-Ras-Nanocluster-Increasing Tumor Growth Inducers.

PubMed

Najumudeen, Arafath K; Posada, Itziar M D; Lectez, Benoit; Zhou, Yong; Landor, Sebastian K-J; Fallarero, Adyary; Vuorela, Pia; Hancock, John; Abankwa, Daniel

2015-12-15

Ras isoforms H-, N-, and K-ras are each mutated in specific cancer types at varying frequencies and have different activities in cell fate control. On the plasma membrane, Ras proteins are laterally segregated into isoform-specific nanoscale signaling hubs, termed nanoclusters. As Ras nanoclusters are required for Ras signaling, chemical modulators of nanoclusters represent ideal candidates for the specific modulation of Ras activity in cancer drug development. We therefore conducted a chemical screen with commercial and in-house natural product libraries using a cell-based H-ras-nanoclustering FRET assay. Next to established Ras inhibitors, such as a statin and farnesyl-transferase inhibitor, we surprisingly identified five protein synthesis inhibitors as positive regulators. Using commonly employed cycloheximide as a representative compound, we show that protein synthesis inhibition increased nanoclustering and effector recruitment specifically of active H-ras but not of K-ras. Consistent with these data, cycloheximide treatment activated both Erk and Akt kinases and specifically promoted H-rasG12V-induced, but not K-rasG12V-induced, PC12 cell differentiation. Intriguingly, cycloheximide increased the number of mammospheres, which are enriched for cancer stem cells. Depletion of H-ras in combination with cycloheximide significantly reduced mammosphere formation, suggesting an exquisite synthetic lethality. The potential of cycloheximide to promote tumor cell growth was also reflected in its ability to increase breast cancer cell tumors grown in ovo. These results illustrate the possibility of identifying Ras-isoform-specific modulators using nanocluster-directed screening. They also suggest an unexpected feedback from protein synthesis inhibition to Ras signaling, which might present a vulnerability in certain tumor cell types.

Platelet-derived growth factor-dependent association of the GTPase-activating protein of Ras and Src.

PubMed Central

Schlesinger, T K; Demali, K A; Johnson, G L; Kazlauskas, A

1999-01-01

Here we report that the platelet-derived growth factor beta receptor (betaPDGFR) is not the only tyrosine kinase able to associate with the GTPase-activating protein of Ras (RasGAP). The interaction of non-betaPDGFR kinase(s) with RasGAP was dependent on stimulation with platelet-derived growth factor (PDGF) and seemed to require tyrosine phosphorylation of RasGAP. Because the tyrosine phosphorylation site of RasGAP is in a sequence context that is favoured by the Src homology 2 ('SH2') domain of Src family members, we tested the possibility that Src was the kinase that associated with RasGAP. Indeed, Src interacted with phosphorylated RasGAP fusion proteins; immunodepletion of Src markedly decreased the recovery of the RasGAP-associated kinase activity. Thus PDGF-dependent tyrosine phosphorylation of RasGAP results in the formation of a complex between RasGAP and Src. To begin to address the relevance of these observations, we focused on the consequences of the interaction of Src and RasGAP. We found that a receptor mutant that did not activate Src was unable to efficiently mediate the tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Taken together, these observations support the following hypothesis. When RasGAP is recruited to the betaPDGFR, it is phosphorylated and associates with Src. Once bound to RasGAP, Src is no longer able to promote the phosphorylation of PLCgamma. This hypothesis offers a mechanistic explanation for our previously published findings that the recruitment of RasGAP to the betaPDGFR attenuates the tyrosine phosphorylation of PLCgamma. Finally, these findings suggest a novel way in which RasGAP negatively regulates signal relay by the betaPDGFR. PMID:10567236

Genetic Validation of Cell Proliferation via Ras-Independent Activation of the Raf/Mek/Erk Pathway.

PubMed

Lechuga, Carmen G; Simón-Carrasco, Lucía; Jacob, Harrys K C; Drosten, Matthias

2017-01-01

Signaling transmitted by the Ras family of small GTPases (H-, N-, and K-Ras) is essential for proliferation of mouse embryonic fibroblasts (MEFs). However, constitutive activation of the downstream Raf/Mek/Erk pathway can bypass the requirement for Ras proteins and allow cells to proliferate in the absence of the three Ras isoforms. Here we describe a protocol for a colony formation assay that permits evaluating the role of candidate proteins that are positive or negative regulators of cell proliferation mediated via Ras-independent Raf/Mek/Erk pathway activation. K-Ras lox (H-Ras -/- , N-Ras -/- , K-Ras lox/lox , RERT ert/ert ) MEFs are infected with retro- or lentiviral vectors expressing wild-type or constitutively activated candidate cDNAs, shRNAs, or sgRNAs in combination with Cas9 to ascertain the possibility of candidate proteins to function either as an activator or inhibitor of Ras-independent Raf/Mek/Erk activation. These cells are then seeded in the absence or presence of 4-Hydroxytamoxifen (4-OHT), which activates the resident CreERT2 alleles resulting in elimination of the conditional K-Ras alleles and ultimately generating Rasless cells. Colony formation in the presence of 4-OHT indicates cell proliferation via Ras-independent Raf/Mek/Erk activation.

Regulation of Son of sevenless by the membrane-actin linker protein ezrin

PubMed Central

Geißler, Katja J.; Jung, M. Juliane; Riecken, Lars Björn; Sperka, Tobias; Cui, Yan; Schacke, Stephan; Merkel, Ulrike; Markwart, Robby; Rubio, Ignacio; Than, Manuel E.; Breithaupt, Constanze; Peuker, Sebastian; Seifert, Reinhard; Kaupp, Ulrich Benjamin; Herrlich, Peter; Morrison, Helen

2013-01-01

Receptor tyrosine kinases participate in several signaling pathways through small G proteins such as Ras (rat sarcoma). An important component in the activation of these G proteins is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. For optimal activity, a second Ras molecule acts as an allosteric activator by binding to a second Ras-binding site within SOS. This allosteric Ras-binding site is blocked by autoinhibitory domains of SOS. We have reported recently that Ras activation also requires the actin-binding proteins ezrin, radixin, and moesin. Here we report the mechanism by which ezrin modulates SOS activity and thereby Ras activation. Active ezrin enhances Ras/MAPK signaling and interacts with both SOS and Ras in vivo and in vitro. Moreover, in vitro kinetic assays with recombinant proteins show that ezrin also is important for the activity of SOS itself. Ezrin interacts with GDP-Ras and with the Dbl homology (DH)/pleckstrin homology (PH) domains of SOS, bringing GDP-Ras to the proximity of the allosteric site of SOS. These actions of ezrin are antagonized by the neurofibromatosis type 2 tumor-suppressor protein merlin. We propose an additional essential step in SOS/Ras control that is relevant for human cancer as well as all physiological processes involving Ras. PMID:24297905

Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.

PubMed

Han, Chang Woo; Jeong, Mi Suk; Jang, Se Bok

2017-09-16

Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines. However, the specific molecular mechanism by which H-REV107 inhibits Ras is still unknown. In the present study, we suggest that H-REV107 forms a strong complex with activating oncogenic mutation Q61H K-Ras from various biochemical binding assays and modeled structures. In addition, the interaction sites between K-Ras and H-REV107 were predicted based on homology modeling. Here, we found that some structure-based mutants of the K-Ras disrupted the complex formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. Copyright © 2017 Elsevier Inc. All rights reserved.

Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2010-08-01

Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

RENAL MICROVASCULAR DISEASE DETERMINES THE RESPONSES TO REVASCULARIZATION IN EXPERIMENTAL RENOVASCULAR DISEASE

PubMed Central

Chade, Alejandro R.; Kelsen, Silvia

2011-01-01

Background Percutaneous trasluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolve renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. Methods and Results RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 was infused intra-renally (RAS+VEGF, 0.05 µg/kg). Single-kidney function was assessed in all pigs in vivo using ultra-fast CT after 6 weeks. Half of the RAS/RAS+VEGF completed their observation, and the other half underwent PTRA, VEGF was repeated, and CT studies repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex-vivo using 3D micro-CT, and renal fibrosis quantified. Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Conclusion Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage. PMID:20587789

Palmitoylation regulates vesicular trafficking of R-Ras to membrane ruffles and effects on ruffling and cell spreading

PubMed Central

Wurtzel, Jeremy G.T.; Kumar, Puneet; Goldfinger, Lawrence E.

2012-01-01

In this study we investigated the dynamics of R-Ras intracellular trafficking and its contributions to the unique roles of R-Ras in membrane ruffling and cell spreading. Wild type and constitutively active R-Ras localized to membranes of both Rab11- and transferrin-positive and -negative vesicles, which trafficked anterograde to the leading edge in migrating cells. H-Ras also co-localized with R-Ras in many of these vesicles in the vicinity of the Golgi, but R-Ras and H-Ras vesicles segregated proximal to the leading edge, in a manner dictated by the C-terminal membrane-targeting sequences. These segregated vesicle trafficking patterns corresponded to distinct modes of targeting to membrane ruffles at the leading edge. Geranylgeranylation was required for membrane anchorage of R-Ras, whereas palmitoylation was required for exit from the Golgi in post-Golgi vesicle membranes and trafficking to the plasma membrane. R-Ras vesicle membranes did not contain phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), whereas R-Ras co-localized with PtdIns(3,4,5)P3 in membrane ruffles. Finally, palmitoylation-deficient R-Ras blocked membrane ruffling, R-Ras/PI3-kinase interaction, enrichment of PtdIns(3,4,5)P3 at the plasma membrane, and R-Ras-dependent cell spreading. Thus, lipid modification of R-Ras dictates its vesicle trafficking, targeting to membrane ruffles, and its unique roles in localizing PtdIns(3,4,5)P3 to ruffles and promoting cell spreading. PMID:22751447

Application of web-GIS approach for climate change study

NASA Astrophysics Data System (ADS)

Okladnikov, Igor; Gordov, Evgeny; Titov, Alexander; Bogomolov, Vasily; Martynova, Yuliya; Shulgina, Tamara

2013-04-01

Georeferenced datasets are currently actively used in numerous applications including modeling, interpretation and forecast of climatic and ecosystem changes for various spatial and temporal scales. Due to inherent heterogeneity of environmental datasets as well as their huge size which might constitute up to tens terabytes for a single dataset at present studies in the area of climate and environmental change require a special software support. A dedicated web-GIS information-computational system for analysis of georeferenced climatological and meteorological data has been created. It is based on OGC standards and involves many modern solutions such as object-oriented programming model, modular composition, and JavaScript libraries based on GeoExt library, ExtJS Framework and OpenLayers software. The main advantage of the system lies in a possibility to perform mathematical and statistical data analysis, graphical visualization of results with GIS-functionality, and to prepare binary output files with just only a modern graphical web-browser installed on a common desktop computer connected to Internet. Several geophysical datasets represented by two editions of NCEP/NCAR Reanalysis, JMA/CRIEPI JRA-25 Reanalysis, ECMWF ERA-40 Reanalysis, ECMWF ERA Interim Reanalysis, MRI/JMA APHRODITE's Water Resources Project Reanalysis, DWD Global Precipitation Climatology Centre's data, GMAO Modern Era-Retrospective analysis for Research and Applications, meteorological observational data for the territory of the former USSR for the 20th century, results of modeling by global and regional climatological models, and others are available for processing by the system. And this list is extending. Also a functionality to run WRF and "Planet simulator" models was implemented in the system. Due to many preset parameters and limited time and spatial ranges set in the system these models have low computational power requirements and could be used in educational workflow for better understanding of basic climatological and meteorological processes. The Web-GIS information-computational system for geophysical data analysis provides specialists involved into multidisciplinary research projects with reliable and practical instruments for complex analysis of climate and ecosystems changes on global and regional scales. Using it even unskilled user without specific knowledge can perform computational processing and visualization of large meteorological, climatological and satellite monitoring datasets through unified web-interface in a common graphical web-browser. This work is partially supported by the Ministry of education and science of the Russian Federation (contract #8345), SB RAS project VIII.80.2.1, RFBR grant #11-05-01190a, and integrated project SB RAS #131.

Dragging ras back in the ring.

PubMed

Stephen, Andrew G; Esposito, Dominic; Bagni, Rachel K; McCormick, Frank

2014-03-17

Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras oncoproteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

The RAS mutation status predicts survival in patients undergoing hepatic resection for colorectal liver metastases: The results from a genetic analysis of all-RAS.

PubMed

Amikura, Katsumi; Akagi, Kiwamu; Ogura, Toshiro; Takahashi, Amane; Sakamoto, Hirohiko

2018-03-01

We investigated the impact of mutations in KRAS exons 3-4 and NRAS exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients with colorectal liver metastasis (CLM) undergoing hepatic resection. We analyzed 421 samples from CLM patients for their all-RAS mutation status to compare the overall survival rate (OS), recurrence-free survival rate (RFS), and the pattern of recurrence between the patients with and without RAS mutations. RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding 79 patients who received anti-EGFR antibody therapy, 168 were classified as all-RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors associated with OS and RFS identified the RAS status as an independent factor (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024). Recurrence with lung metastasis was observed significantly more frequent in patients with RAS mutations than in patients with RAS wild-type (P = 0.0005). Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy. © 2017 Wiley Periodicals, Inc.

Ras, an Actor on Many Stages

PubMed Central

Arozarena, Imanol; Calvo, Fernando; Crespo, Piero

2011-01-01

Among the wealth of information that we have gathered about Ras in the past decade, the introduction of the concept of space in the field has constituted a major revolution that has enabled many pieces of the Ras puzzle to fall into place. In the early days, it was believed that Ras functioned exclusively at the plasma membrane. Today, we know that within the plasma membrane, the 3 Ras isoforms—H-Ras, K-Ras, and N-Ras—occupy different microdomains and that these isoforms are also present and active in endomembranes. We have also discovered that Ras proteins are not statically associated with these localizations; instead, they traffic dynamically between compartments. And we have learned that at these localizations, Ras is under site-specific regulatory mechanisms, distinctively engaging effector pathways and switching on diverse genetic programs to generate different biological responses. All of these processes are possible in great part due to the posttranslational modifications whereby Ras proteins bind to membranes and to regulatory events such as phosphorylation and ubiquitination that Ras is subject to. As such, space and these control mechanisms act in conjunction to endow Ras signals with an enormous signal variability that makes possible its multiple biological roles. These data have established the concept that the Ras signal, instead of being one single, homogeneous entity, results from the integration of multiple, site-specified subsignals, and Ras has become a paradigm of how space can differentially shape signaling. PMID:21779492

Physical Compatibility of Micafungin With Sodium Bicarbonate Hydration Fluids Commonly Used With High-Dose Methotrexate Chemotherapy.

PubMed

Joiner, Logan C; Tynes, Clay; Arnold, John; Miller, Rachel R; Gorman, Greg

2018-04-01

Purpose: The purpose of this study was to determine the physical compatibility of micafungin with commonly used concentrations of sodium bicarbonate hydration fluids administered via a Y-site connected to a central venous catheter (Y-site/CVC). Methods: Micafungin sodium (evaluated concentration of 1.5 mg/mL) was combined in a 3:1 (vehicle:drug) ratio with the following commonly used hydration vehicles: 40 mEq/L sodium bicarbonate in 5% dextrose in water with ¼ normal saline (40SB-D5W-1/4NS), 75 mEq/L sodium bicarbonate in D5W (75SB-D5W), and 154 mEq/L sodium bicarbonate in D5W (154SB-D5W). A 3:1 ratio was used based on the flow rates (typically 125 mL/m 2 /h for bicarbonate-containing vehicles and 50 mL/h for micafungin) of the corresponding solutions in a clinical setting. Visual observations recorded to determine physical compatibility included visual inspection against different backgrounds (unaided, black, and white). Other physical observations were as follows: odor, evolution of gas, pH, and turbidity immediately recorded after mixing and at specified time points up to 2 hours. Evaluations at each time point were compared against baseline observation values at Time 0. Results: All combinations tested were found to be compatible up to 2 hours. Time points beyond 2 hours cannot be safely verified as compatible. Conclusion: Micafungin may be administered safely using a Y-site/CVC delivery system with all the vehicles tested in this study.

Communicating about obesity and weight-related topics with children with a physical disability and their families: spina bifida as an example.

PubMed

McPherson, Amy C; Swift, Judy A; Peters, Michelle; Lyons, Julia; Joy Knibbe, Tara; Church, Paige; Chen, Lorry; Farrell, Renée M; Willem Gorter, Jan

2017-04-01

The purpose of this study was to explore the experiences of children with spina bifida (SB), their families and healthcare professionals (HCPs) when discussing weight-related topics. In-depth qualitative interviews were conducted with HCPs from Canadian outpatient SB clinics (n = 13), children aged 6-18 years with SB (n = 17) and their parents (n = 20). Data were analyzed using a phenomenological approach within an interpretative paradigm. Many HCPs were not confident talking about weight, concerned that they would damage relationships with children and families. Parents wanted routine weight surveillance, but were worried about their children's self-esteem if their weight was discussed. They wanted HCPs to acknowledge the challenges of weight management in children with a physical disability and provide specialized solutions. Children wanted a positively framed and tailored approach to weight discussions, although this had generally not been their experience. Stakeholders describe therapeutic relationships that are currently disconnected around the issue of weight and obesity. However, children, parents and HCPs all believed that discussing this topic was critical. Positively framed, strengths-based and tailored approaches to weight-related discussions are warranted. Implications for Rehabilitation Rates of overweight and obesity in children and youth with physical disabilities are substantially higher than their typically developing peers. Healthcare professionals, children with physical disabilities and families often find weight-related discussions challenging and disconnected. Weight-related discussions should be tailored to the child and family's circumstances and priorities. Positively framed and strengths-based approaches to weight-related discussions are warranted.

Rat embryo cells immortalized with transfected oncogenes are transformed by gamma irradiation.

PubMed

Endlich, B; Salavati, R; Sullivan, T; Ling, C C

1992-12-01

Cesium-137 gamma rays were used to transform rat embryo cells (REC) which were first transfected with activated c-myc or c-Ha-ras oncogenes to produce immortal cell lines (REC:myc and REC:ras). When exposed to 6 Gy of 137Cs gamma rays, some cells became morphologically transformed with focus formation frequencies of approximately 3 x 10(-4) for REC:myc and approximately 1 x 10(-4) for REC:ras, respectively. Cells isolated from foci of gamma-ray-transformed REC:myc (REC:myc:gamma) formed anchorage-independent colonies and were tumorigenic in nude mice, but foci from gamma-ray-transformed REC:ras (REC:ras:gamma) did not exhibit either of these criteria of transformation. Similar to the results with gamma irradiation, we observed a sequence-dependent phenomenon when myc and ras were transfected into REC, one at a time. REC immortalized by ras transfection were not converted to a tumorigenic phenotype by secondary transfection with myc, but REC transfected with myc were very susceptible to transformation by subsequent ras transfection. This suggests that myc-immortalized cells are more permissive to transformation via secondary treatments. In sequentially transfected REC, myc expression was high whether it was transfected first or second, whereas ras expression was highest when the ras gene was transfected secondarily into myc-containing REC. Molecular analysis of REC:ras:gamma transformants showed no alterations in structure of the transfected ras or of the endogenous ras, myc, p53, or fos genes. The expression of ras and p53 was increased in some isolates of REC:ras:gamma, but myc and fos expression were not affected. Similarly, REC:myc:gamma transformants did not demonstrate rearrangement or amplification of the transfected or the endogenous myc genes, or of the potentially cooperating Ha-, Ki-, or N-ras genes. Northern hybridization analysis revealed increased expression of N-ras in two isolates, REC:myc:gamma 33 and gamma 41, but no alterations in the expression of myc, raf, Ha-ras, or Ki-ras genes in any REC:myc transformant. DNA from several transformed REC:myc:gamma cell lines induced focus formation in recipient C3H 10T1/2 and NIH 3T3 cells. The NIH 3T3 foci tested positive when hybridized to a probe for rat repetitive DNA. A detailed analysis of the NIH 3T3 transformants generated from REC:myc:gamma 33 and gamma 41 DNA failed to detect Ha-ras, Ki-ras, raf, neu, trk, abl, fms, or src oncogenes of rat origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Structural Dynamics in Ras and Related Proteins upon Nucleotide Switching.

PubMed

Harrison, Rane A; Lu, Jia; Carrasco, Martin; Hunter, John; Manandhar, Anuj; Gondi, Sudershan; Westover, Kenneth D; Engen, John R

2016-11-20

Structural dynamics of Ras proteins contributes to their activity in signal transduction cascades. Directly targeting Ras proteins with small molecules may rely on the movement of a conserved structural motif, switch II. To understand Ras signaling and advance Ras-targeting strategies, experimental methods to measure Ras dynamics are required. Here, we demonstrate the utility of hydrogen-deuterium exchange (HDX) mass spectrometry (MS) to measure Ras dynamics by studying representatives from two branches of the Ras superfamily, Ras and Rho. A comparison of differential deuterium exchange between active (GMPPNP-bound) and inactive (GDP-bound) proteins revealed differences between the families, with the most notable differences occurring in the phosphate-binding loop and switch II. The P-loop exchange signature correlated with switch II dynamics observed in molecular dynamics simulations focused on measuring main-chain movement. HDX provides a means of evaluating Ras protein dynamics, which may be useful for understanding the mechanisms of Ras signaling, including activated signaling of pathologic mutants, and for targeting strategies that rely on protein dynamics. Copyright © 2016 Elsevier Ltd. All rights reserved.

RasGRP1 opposes proliferative EGFR–SOS1–Ras signals and restricts intestinal epithelial cell growth

PubMed Central

Depeille, Philippe; Henricks, Linda M.; van de Ven, Robert A. H.; Lemmens, Ed; Wang, Chih-Yang; Matli, Mary; Werb, Zena; Haigis, Kevin M.; Donner, David; Warren, Robert; Roose, Jeroen P.

2015-01-01

The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome. Biochemically, we find that RasGRP1 creates a negative feedback loop that limits proliferative EGFR–SOS1–Ras signals in CRC cells. Genetic Rasgrp1 depletion from mice with either an activating mutation in KRas or with aberrant Wnt signalling due to a mutation in Apc resulted in both cases in exacerbated Ras–ERK signalling and cell proliferation. The unexpected opposing cell biological effects of EGFR–RasGRP1 and EGFR–SOS1 signals in the same cell shed light on the intricacy of EGFR-Ras signalling in normal epithelium and carcinoma. PMID:26005835

Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Travers, Timothy; Lopez Bautista, Cesar Augusto; Van, Que

Activation of RAF kinase involves the association of its RAS-binding domain (RBD) and cysteine-rich domain (CRD) with membrane-anchored RAS. However, the overall architecture of the RAS/RBD/CRD ternary complex and the orientations of its constituent domains at the membrane remain unclear. Here in this paper, we have combined all-atom and coarse-grained molecular dynamics (MD) simulations with experimental data to construct and validate a model of membrane-anchored CRD, and used this as a basis to explore models of membrane-anchored RAS/RBD/CRD complex. First, simulations of the CRD revealed that it anchors to the membrane via insertion of its two hydrophobic loops, which ismore » consistent with our NMR measurements of CRD bound to nanodiscs. Simulations of the CRD in the context of membrane-anchored RAS/RBD then show how CRD association with either RAS or RBD could play an unexpected role in guiding the membrane orientations of RAS/RBD. This finding has implications for the formation of RAS-RAS dimers, as different membrane orientations of RAS expose distinct putative dimerization interfaces.« less

Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain

DOE PAGES

Travers, Timothy; Lopez Bautista, Cesar Augusto; Van, Que; ...

2018-05-31

Activation of RAF kinase involves the association of its RAS-binding domain (RBD) and cysteine-rich domain (CRD) with membrane-anchored RAS. However, the overall architecture of the RAS/RBD/CRD ternary complex and the orientations of its constituent domains at the membrane remain unclear. Here in this paper, we have combined all-atom and coarse-grained molecular dynamics (MD) simulations with experimental data to construct and validate a model of membrane-anchored CRD, and used this as a basis to explore models of membrane-anchored RAS/RBD/CRD complex. First, simulations of the CRD revealed that it anchors to the membrane via insertion of its two hydrophobic loops, which ismore » consistent with our NMR measurements of CRD bound to nanodiscs. Simulations of the CRD in the context of membrane-anchored RAS/RBD then show how CRD association with either RAS or RBD could play an unexpected role in guiding the membrane orientations of RAS/RBD. This finding has implications for the formation of RAS-RAS dimers, as different membrane orientations of RAS expose distinct putative dimerization interfaces.« less

p21ras independent down-regulation of ras-induced increases in natural antibody binding during tumor progression.

PubMed

Tough, D F; Feng, X; Chow, D A

1995-01-01

Selective outgrowth of v-H-ras-infected 10T1/2 cells based on the cointroduction of a gene for resistance to geneticin (G418), yielded cells which exhibited an increased capacity to bind polyclonal serum natural antibody (NAb). This demonstrated an NAb-susceptible phase of tumor development which would be a basic requirement for NAb-mediated surveillance of tumors. The ras-oncogene dependence of the high-NAb-binding phenotype provided a model for assessing NAb resistance against ras transformants in vivo and for a comparative analysis of phenotypic and genetic alterations contributing to the progression of ras transformants. Variants were developed through in vitro and in vivo models of tumor progression. T24-H-ras and v-H-ras transformants were isolated in vitro through more rigorous growth conditions, focus formation in the presence of untransformed cells with no selecting drug. These clones expressed p21ras but exhibited little or no increase in NAb binding. Variants recovered following growth from intravenous or threshold subcutaneous (s.c.) inocula of high-NAb-binding ras transformants in syngeneic C3H/HeN mice exhibited decreases in NAb binding but no uniform change in p21ras. Concurring inverse correlations between NAb binding and s.c. tumorigenicity were exhibited by the T24-H-ras transformant clones, the ras transformants grown in vivo, and the v-H-ras-transformed clones isolated in the presence versus the absence of untransformed cells. This consistent inverse correlation, together with the reduced NAb binding of the ras transformants grown in vivo, provides strong evidence that NAb participates in the defense against ras-transformed cells in vivo. The lack of any direct correlation between p21ras expression and the reduction in NAb binding or the increase in tumorigenicity of cells generated through progression in vivo suggested the regulatory action of additional genes. Hybridization studies between high- and low-NAb-binding clones implicated the activation of an additional oncogene and inactivation of an antioncogene in the down-regulation of the ras-induced increases in NAb binding associated with tumor progression.

Using the Intervention Mapping and Behavioral Intervention Technology Frameworks: Development of an mHealth Intervention for Physical Activity and Sedentary Behavior Change.

PubMed

Direito, Artur; Walsh, Deirdre; Hinbarji, Moohamad; Albatal, Rami; Tooley, Mark; Whittaker, Robyn; Maddison, Ralph

2018-06-01

Few interventions to promote physical activity (PA) adapt dynamically to changes in individuals' behavior. Interventions targeting determinants of behavior are linked with increased effectiveness and should reflect changes in behavior over time. This article describes the application of two frameworks to assist the development of an adaptive evidence-based smartphone-delivered intervention aimed at influencing PA and sedentary behaviors (SB). Intervention mapping was used to identify the determinants influencing uptake of PA and optimal behavior change techniques (BCTs). Behavioral intervention technology was used to translate and operationalize the BCTs and its modes of delivery. The intervention was based on the integrated behavior change model, focused on nine determinants, consisted of 33 BCTs, and included three main components: (1) automated capture of daily PA and SB via an existing smartphone application, (2) classification of the individual into an activity profile according to their PA and SB, and (3) behavior change content delivery in a dynamic fashion via a proof-of-concept application. This article illustrates how two complementary frameworks can be used to guide the development of a mobile health behavior change program. This approach can guide the development of future mHealth programs.

EphA2 Drives the Segregation of Ras-Transformed Epithelial Cells from Normal Neighbors.

PubMed

Porazinski, Sean; de Navascués, Joaquín; Yako, Yuta; Hill, William; Jones, Matthew Robert; Maddison, Robert; Fujita, Yasuyuki; Hogan, Catherine

2016-12-05

In epithelial tissues, cells expressing oncogenic Ras (hereafter RasV12 cells) are detected by normal neighbors and as a result are often extruded from the tissue [1-6]. RasV12 cells are eliminated apically, suggesting that extrusion may be a tumor-suppressive process. Extrusion depends on E-cadherin-based cell-cell adhesions and signaling to the actin-myosin cytoskeleton [2, 6]. However, the signals underlying detection of the RasV12 cell and triggering extrusion are poorly understood. Here we identify differential EphA2 signaling as the mechanism by which RasV12 cells are detected in epithelial cell sheets. Cell-cell interactions between normal cells and RasV12 cells trigger ephrin-A-EphA2 signaling, which induces a cell repulsion response in RasV12 cells. Concomitantly, RasV12 cell contractility increases in an EphA2-dependent manner. Together, these responses drive the separation of RasV12 cells from normal cells. In the absence of ephrin-A-EphA2 signals, RasV12 cells integrate with normal cells and adopt a pro-invasive morphology. We also show that Drosophila Eph (DEph) is detected in segregating clones of RasV12 cells and is functionally required to drive segregation of RasV12 cells in vivo, suggesting that our in vitro findings are conserved in evolution. We propose that expression of RasV12 in single or small clusters of cells within a healthy epithelium creates ectopic EphA2 boundaries, which drive the segregation and elimination of the transformed cell from the tissue. Thus, deregulation of Eph/ephrin would allow RasV12 cells to go undetected and expand within an epithelium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer.

PubMed

Kim, Tae Won; Peeters, Marc; Thomas, Anne L; Gibbs, Peter; Hool, Kristina; Zhang, Jianqi; Ang, Agnes; Bach, Bruce Allen; Price, Timothy

2018-06-13

The accumulation of emergent RAS mutations during anti-epidermal growth factor receptor (EGFR) therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status. This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the Plasma Select -R™ 64-gene panel at 0.1% sensitivity. Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival (OS) for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval: 11.5-15.4) and 7.9 months (6.4-9.6), respectively ( P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations. Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Copyright ©2018, American Association for Cancer Research.

A New Strategy to Control and Eradicate "Undruggable" Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology.

PubMed

Van Sciver, Robert E; Lee, Michael P; Lee, Caroline Dasom; Lafever, Alex C; Svyatova, Elizaveta; Kanda, Kevin; Colliver, Amber L; Siewertsz van Reesema, Lauren L; Tang-Tan, Angela M; Zheleva, Vasilena; Bwayi, Monicah N; Bian, Minglei; Schmidt, Rebecca L; Matrisian, Lynn M; Petersen, Gloria M; Tang, Amy H

2018-05-14

Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely "undruggable". Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper RAS signaling. Guided by molecular insights and core principles obtained from developmental and evolutionary biology, we propose an anti-SIAH-centered anti-K-RAS strategy as a logical and alternative anticancer strategy to dampen uncontrolled K-RAS hyperactivation and halt tumor growth and metastasis in pancreatic cancer. The clinical utility of developing SIAH as both a tumor-specific and therapy-responsive biomarker, as well as a viable anti-K-RAS drug target, is logically simple and conceptually innovative. SIAH clearly constitutes a major tumor vulnerability and K-RAS signaling bottleneck in pancreatic ductal adenocarcinoma (PDAC). Given the high degree of evolutionary conservation in the K-RAS/SIAH signaling pathway, an anti-SIAH-based anti-PDAC therapy will synergize with covalent K-RAS inhibitors and direct K-RAS targeted initiatives to control and eradicate pancreatic cancer in the future.

Does Harvey-Ras gene expression lead to oral squamous cell carcinoma? A clinicopathological aspect

PubMed Central

Krishna, Akhilesh; Singh, Shraddha; Singh, Vineeta; Kumar, Vijay; Singh, Uma Shankar; Sankhwar, Satya Narayan

2018-01-01

Background: Harvey-Ras (H-Ras) is an important guanosine triphosphatase protein for the regulation of cellular growth and survival. Altered Ras signaling has been observed in different types of cancer either by gene amplification and/or mutation. The H-Ras oncogene mutations are well reported, but expression of the H-Ras gene is still unknown. Objective: This study aimed to examine both protein and messenger-RNA (mRNA) expressions of H-Ras in oral squamous cell carcinoma (OSCC) and analyzed the association with risk habits and the clinicopathological profile of cases. Methodology: A total of 65 tissue specimens of OSCC (case group) and equal number of normal tissues (control group) were included in this study. H-Ras protein and mRNA expressions were analyzed using immunohistochemical and quantitative real time-polymerase chain reaction techniques, respectively. Results: The H-Ras protein was significantly overexpressed in the oral carcinoma group compared to the normal group (P = 0.03). Most of the OSCC cases showed positive staining with moderate expression, while negative and moderate staining was high in the control group. The majority of H-Ras positive cases were found in individuals with multiple risk habits including tobacco chewing. The risk of H-Ras positivity was 1.46 times higher in smokers than non-smokers. H-Ras positivity increased in cases affected with buccal mucosa site and higher grade of carcinoma. Relative mRNA level of H-Ras was significantly elevated in oral carcinoma as compared with the control group (P ≤ 0.001). Protein and mRNA levels of H-Ras in case group was poorly correlated. Conclusion: H-Ras oncogene expression was markedly higher in oral carcinoma, and it can be a prognostic marker and target for an effective molecular therapy. PMID:29731559

Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target

PubMed Central

Chen, Mo; Peters, Alec; Huang, Tao; Nan, Xiaolin

2016-01-01

The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology. PMID:26423697

Improvements on the optical properties of Ge-Sb-Se chalcogenide glasses with iodine incorporation

NASA Astrophysics Data System (ADS)

Jiang, Chen; Wang, Xunsi; Zhu, Qingde; Nie, Qiuhua; Zhu, Minming; Zhang, Peiquan; Dai, Shixun; Shen, Xiang; Xu, Tiefeng; Cheng, Ci; Liao, Fangxing; Liu, Zijun; Zhang, Xianghua

2015-11-01

Decreasing glass network defects and improving optical transmittance are essential work for material researchers. We studied the function of halogen iodine (I) acting as a glass network modifier in Ge-Sb-Se-based chalcogenide glass system. A systematic series of Ge20Sb5Se75-xIx (x = 0, 5, 10, 15, 20 at.%) infrared (IR) chalcohalide glasses were investigated to decrease the weak absorption tail (WAT) and improve the mid-IR transparency. The mechanisms of the halogen I affecting the physical, thermal, and optical properties of Se-based chalcogenide glasses were reported. The structural evolutions of these glasses were also revealed by Raman spectroscopy and camera imaging. The progressive substitution of I for Se increased the optical bandgap. The WAT and scatting loss significantly decreased corresponding to the progressive decrease in structural defects caused by dangling bands and structure defects in the original Ge20Sb5Se75 glass. The achieved maximum IR transparency of Ge-Sb-Se-I glasses can reach up to 80% with an effective transmission window between 0.94 μm and 17 μm, whereas the absorption coefficient decreased to 0.029 cm-1 at 10.16 μm. Thus, these materials are promising candidates for developing low-loss IR fibers.

Validation of the VitaBit Sit–Stand Tracker: Detecting Sitting, Standing, and Activity Patterns

PubMed Central

Plasqui, Guy

2018-01-01

Sedentary behavior (SB) has detrimental consequences and cannot be compensated for through moderate-to-vigorous physical activity (PA). In order to understand and mitigate SB, tools for measuring and monitoring SB are essential. While current direct-to-customer wearables focus on PA, the VitaBit validated in this study was developed to focus on SB. It was tested in a laboratory and in a free-living condition, comparing it to direct observation and to a current best-practice device, the ActiGraph, on a minute-by-minute basis. In the laboratory, the VitaBit yielded specificity and negative predictive rates (NPR) of above 91.2% for sitting and standing, while sensitivity and precision ranged from 74.6% to 85.7%. For walking, all performance values exceeded 97.3%. In the free-living condition, the device revealed performance of over 72.6% for sitting with the ActiGraph as criterion. While sensitivity and precision for standing and walking ranged from 48.2% to 68.7%, specificity and NPR exceeded 83.9%. According to the laboratory findings, high performance for sitting, standing, and walking makes the VitaBit eligible for SB monitoring. As the results are not transferrable to daily life activities, a direct observation study in a free-living setting is recommended. PMID:29543766

Waist Circumference and Objectively Measured Sedentary Behavior in Rural School Adolescents.

PubMed

Machado-Rodrigues, Aristides M; Coelho E Silva, Manuel J; Ribeiro, Luís P; Fernandes, Romulo; Mota, Jorge; Malina, Robert M

2016-01-01

Research on relationships between lifestyle behaviors and adiposity in school youth is potentially important for identifying subgroups at risk. This study evaluates the associations between waist circumference (WC) and objective measures of sedentary behavior (SB) in a sample of rural school adolescents. The sample included 254 students (114 boys, 140 girls), 13-16 years of age, from rural regions of the Portuguese midlands. Height, weight, and WC were measured. Cardiorespiratory fitness (CRF) was assessed with the 20-m shuttle-run test. An uniaxial GT1M accelerometer was used to obtain 5 consecutive days of physically activity (PA) and SB. Multiple linear regression was used to test associations between WC and SB, adjusted for several potential confounders (age, sex, PA, CRF, parental education). SB was not significantly associated with the WC, neither in the unadjusted model nor after adjustment for all potential confounders. In the final model, the unique significant predictor of the WC was cardiorespiratory fitness (β = -0.82; 95% confidence interval [CI], -1.02 to -0.62). WC was not independently associated with SB time in rural school adolescents. Future research is claimed among rural adolescents in different geographic contexts to try to clarify recent findings of less studied communities. © 2015, American School Health Association.

Endomembrane H-Ras Controls Vascular Endothelial Growth Factor-induced Nitric-oxide Synthase-mediated Endothelial Cell Migration*

PubMed Central

Haeussler, Dagmar J.; Pimentel, David R.; Hou, Xiuyun; Burgoyne, Joseph R.; Cohen, Richard A.; Bachschmid, Markus M.

2013-01-01

We demonstrate for the first time that endomembrane-delimited H-Ras mediates VEGF-induced activation of endothelial nitric-oxide synthase (eNOS) and migratory response of human endothelial cells. Using thiol labeling strategies and immunofluorescent cell staining, we found that only 31% of total H-Ras is S-palmitoylated, tethering the small GTPase to the plasma membrane but leaving the function of the large majority of endomembrane-localized H-Ras unexplained. Knockdown of H-Ras blocked VEGF-induced PI3K-dependent Akt (Ser-473) and eNOS (Ser-1177) phosphorylation and nitric oxide-dependent cell migration, demonstrating the essential role of H-Ras. Activation of endogenous H-Ras led to recruitment and phosphorylation of eNOS at endomembranes. The loss of migratory response in cells lacking endogenous H-Ras was fully restored by modest overexpression of an endomembrane-delimited H-Ras palmitoylation mutant. These studies define a newly recognized role for endomembrane-localized H-Ras in mediating nitric oxide-dependent proangiogenic signaling. PMID:23548900

Differences in the Regulation of K-Ras and H-Ras Isoforms by Monoubiquitination*

PubMed Central

Baker, Rachael; Wilkerson, Emily M.; Sumita, Kazutaka; Isom, Daniel G.; Sasaki, Atsuo T.; Dohlman, Henrik G.; Campbell, Sharon L.

2013-01-01

Ras GTPases are signaling switches that control critical cellular processes including gene expression, differentiation, and apoptosis. The major Ras isoforms (K, H, and N) contain a conserved core GTPase domain, but have distinct biological functions. Among the three Ras isoforms there are clear differences in post-translational regulation, which contribute to differences in localization and signaling output. Modification by ubiquitination was recently reported to activate Ras signaling in cells, but the mechanisms of activation are not well understood. Here, we show that H-Ras is activated by monoubiquitination and that ubiquitination at Lys-117 accelerates intrinsic nucleotide exchange, thereby promoting GTP loading. This mechanism of Ras activation is distinct from K-Ras monoubiquitination at Lys-147, which leads to impaired regulator-mediated GTP hydrolysis. These findings reveal that different Ras isoforms are monoubiquitinated at distinct sites, with distinct mechanisms of action, but with a common ability to chronically activate the protein in the absence of a receptor signal or oncogenic mutation. PMID:24247240

Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.

PubMed

Burns, Michael C; Sun, Qi; Daniels, R Nathan; Camper, DeMarco; Kennedy, J Phillip; Phan, Jason; Olejniczak, Edward T; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2014-03-04

Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

Enhanced MET Translation and Signaling Sustains K-Ras-Driven Proliferation under Anchorage-Independent Growth Conditions.

PubMed

Fujita-Sato, Saori; Galeas, Jacqueline; Truitt, Morgan; Pitt, Cameron; Urisman, Anatoly; Bandyopadhyay, Sourav; Ruggero, Davide; McCormick, Frank

2015-07-15

Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to chemotherapeutic drugs as well as molecular targeting agents. Although numerous approaches are ongoing to find effective ways to treat these tumors, there are still no effective therapies for K-Ras mutant cancer patients. Here we report that K-Ras mutant cancers are more dependent on K-Ras in anchorage-independent culture conditions than in monolayer culture conditions. In seeking to determine mechanisms that contribute to the K-Ras dependency in anchorage-independent culture conditions, we discovered the involvement of Met in K-Ras-dependent, anchorage-independent cell growth. The Met signaling pathway is enhanced and plays an indispensable role in anchorage-independent growth even in cells in which Met is not amplified. Indeed, Met expression is elevated under anchorage-independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, in spite of a global downregulation of mRNA translation during anchorage-independent growth, we find that Met mRNA translation is specifically enhanced under these conditions. Importantly, ectopic expression of an active Met mutant rescues K-Ras ablation-derived growth suppression, indicating that K-Ras-mediated Met expression drives "K-Ras addiction" in anchorage-independent conditions. Our results indicate that enhanced Met expression and signaling is essential for anchorage-independent growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors of Met could be effective for K-Ras mutant tumor patients. ©2015 American Association for Cancer Research.

N-ras Mutation Detection by Pyrosequencing in Adult Patients with Acute Myeloid Leukemia at a Single Institution

PubMed Central

Jeong, Ji Hun; Park, Soon Ho; Park, Mi Jung; Kim, Moon Jin; Kim, Kyung Hee; Park, Pil Whan; Seo, Yiel Hea; Lee, Jae Hoon; Park, Jinny; Hong, Junshik

2013-01-01

Background N-ras mutations are one of the most commonly detected abnormalities of myeloid origin. N-ras mutations result in a constitutively active N-ras protein that induces uncontrolled cell proliferation and inhibits apoptosis. We analyzed N-ras mutations in adult patients with AML at a particular institution and compared pyrosequencing analysis with a direct sequencing method for the detection of N-ras mutations. Methods We analyzed 90 bone marrow samples from 83 AML patients. We detected N-ras mutations in codons 12, 13, and 61 using the pyrosequencing method and subsequently confirmed all data by direct sequencing. Using these methods, we screened the N-ras mutation quantitatively and determined the incidence and characteristic of N-ras mutation. Results The incidence of N-ras mutation was 7.2% in adult AML patients. The patients with N-ras mutations showed significant higher hemoglobin levels (P=0.022) and an increased incidence of FLT3 mutations (P=0.003). We observed 3 cases with N-ras mutations in codon 12 (3.6%), 2 cases in codon 13 (2.4%), and 1 case in codon 61 (1.2%). All the mutations disappeared during chemotherapy. Conclusions There is a low incidence (7.2%) of N-ras mutations in AML patients compared with other populations. Similar data is obtained by both pyrosequencing and direct sequencing. This study showed the correlation between the N-ras mutation and the therapeutic response. However, pyrosequencing provides quantitative data and is useful for monitoring therapeutic responses. PMID:23667841

Enhanced MET translation and signaling sustains K-Ras driven proliferation under anchorage-independent growth conditions

PubMed Central

Fujita-Sato, Saori; Galeas, Jacqueline; Truitt, Morgan; Pitt, Cameron; Urisman, Anatoly; Bandyopadhyay, Sourav; Ruggero, Davide; McCormick, Frank

2015-01-01

Oncogenic K-Ras mutation occurs frequently in several types of cancers including pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to chemotherapeutic drugs as well as molecular targeting agents. Although numerous approaches are ongoing to find effective ways to treat these tumors, there are still no effective therapies for K-Ras mutant cancer patients. Here we report that K-Ras mutant cancers are more dependent on K-Ras in anchorage independent culture conditions than in monolayer culture conditions. In seeking to determine mechanisms that contribute to the K-Ras dependency in anchorage independent culture conditions, we discovered the involvement of Met in K-Ras-dependent, anchorage independent cell growth. The Met signaling pathway is enhanced and plays an indispensable role in anchorage independent growth even in cells in which Met is not amplified. Indeed, Met expression is elevated under anchorage-independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, in spite of a global down-regulation of mRNA translation during anchorage independent growth, we find that Met mRNA translation is specifically enhanced under these conditions. Importantly, ectopic expression of an active Met mutant rescues K-Ras ablation-derived growth suppression, indicating that K-Ras mediated Met expression drives “K-Ras addiction” in anchorage independent conditions. Our results indicate that enhanced Met expression and signaling is essential for anchorage independent growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors of Met could be effective for K-Ras mutant tumor patients. PMID:25977330

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

The Influence of Weather Variation, Urban Design and Built Environment on Objectively Measured Sedentary Behaviour in Children.

PubMed

Katapally, Tarun Reddy; Rainham, Daniel; Muhajarine, Nazeem

2016-01-01

With emerging evidence indicating that independent of physical activity, sedentary behaviour (SB) can be detrimental to health, researchers are increasingly aiming to understand the influence of multiple contexts such as urban design and built environment on SB. However, weather variation, a factor that continuously interacts with all other environmental variables, has been consistently underexplored. This study investigated the influence of diverse environmental exposures (including weather variation, urban design and built environment) on SB in children. This cross-sectional observational study is part of an active living research initiative set in the Canadian prairie city of Saskatoon. Saskatoon's neighbourhoods were classified based on urban street design into grid-pattern, fractured grid-pattern and curvilinear types of neighbourhoods. Diverse environmental exposures were measured including, neighbourhood built environment, and neighbourhood and household socioeconomic environment. Actical accelerometers were deployed between April and June 2010 (spring-summer) to derive SB of 331 10-14 year old children in 25 one week cycles. Each cycle of accelerometry was conducted on a different cohort of children within the total sample. Accelerometer data were matched with localized weather patterns derived from Environment Canada weather data. Multilevel modeling using Hierarchical Linear and Non-linear Modeling software was conducted by factoring in weather variation to depict the influence of diverse environmental exposures on SB. Both weather variation and urban design played a significant role in SB. After factoring in weather variation, it was observed that children living in grid-pattern neighbourhoods closer to the city centre (with higher diversity of destinations) were less likely to be sedentary. This study demonstrates a methodology that could be replicated to integrate geography-specific weather patterns with existing cross-sectional accelerometry data to understand the influence of urban design and built environment on SB in children.

Proton-neutron multiplet states in {sup 112}Sb

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fayez-Hassan, M.; Gulyas, J.; Dombradi, Z.

1997-05-01

Excited states of {sup 112}Sb were investigated through the {sup 112}Sn(p,n{gamma}){sup 112}Sb reaction. {gamma}-ray, {gamma}{gamma}-coincidence, and internal conversion electron spectra were measured with Ge(HP) {gamma} and superconducting magnetic lens plus Si(Li) electron spectrometers at 8.5, 8.9, 9.1, and 9.3 MeV bombarding proton energies. A significantly extended level scheme was constructed. Spins and parities have been assigned to the levels from Hauser-Feshbach analysis of reaction cross sections, internal conversion coefficients, angular distribution of the {gamma} rays, and decay properties of the states. The low lying states were assigned to proton-neutron multiplets on the basis of their decay properties. The energy splittingmore » of these multiplets have been calculated using the parabolic rule. {copyright} {ital 1997} {ital The American Physical Society}« less

Influence of Sub-grid-Scale Isentropic Transports on McRAS Evaluations using ARM-CART SCM Datasets

NASA Technical Reports Server (NTRS)

Sud, Y. C.; Walker, G. K.; Tao, W. K.

2004-01-01

In GCM-physics evaluations with the currently available ARM-CART SCM datasets, McRAS produced very similar character of near surface errors of simulated temperature and humidity containing typically warm and moist biases near the surface and cold and dry biases aloft. We argued it must have a common cause presumably rooted in the model physics. Lack of vertical adjustment of horizontal transport was thought to be a plausible source. Clearly, debarring such a freedom would force the incoming air to diffuse into the grid-cell which would naturally bias the surface air to become warm and moist while the upper air becomes cold and dry, a characteristic feature of McRAS biases. Since, the errors were significantly larger in the two winter cases that contain potentially more intense episodes of cold and warm advective transports, it further reaffirmed our argument and provided additional motivation to introduce the corrections. When the horizontal advective transports were suitably modified to allow rising and/or sinking following isentropic pathways of subgrid scale motions, the outcome was to cool and dry (or warm and moisten) the lower (or upper) levels. Ever, crude approximations invoking such a correction reduced the temperature and humidity biases considerably. The tests were performed on all the available ARM-CART SCM cases with consistent outcome. With the isentropic corrections implemented through two different numerical approximations, virtually similar benefits were derived further confirming the robustness of our inferences. These results suggest the need for insentropic advective transport adjustment in a GCM due to subgrid scale motions.

Ambient CdCl{sub 2} treatment on CdS buffer layer for improved performance of Sb{sub 2}Se{sub 3} thin film photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Liang; Luo, Miao; Qin, Sikai

2015-10-05

Antimony selenide (Sb{sub 2}Se{sub 3}) is appealing as a promising light absorber because of its intrinsically benign grain boundaries, suitable band gap (∼1.1 eV), strong absorption coefficient, and relatively environmentally friendly constituents. Recently, we achieved a certified 5.6% efficiency Sb{sub 2}Se{sub 3} thin film solar cell with the assistance of ambient CdCl{sub 2} treatment on the CdS buffer layer. Here, we focused on investigating the underlying mechanism from a combined materials and device physics perspective applying current density-voltage (J-V) fitting analysis, atomic force microscope, X-ray photoelectron spectroscopy, fluorescence, and UV–Vis transmission spectroscopy. Our results indicated that ambient CdCl{sub 2} treatment onmore » CdS film not only improved CdS grain size and quality, but also incorporated Cl and more O into the film, both of which can significantly improve the heterojunction quality and device performance of CdS/Sb{sub 2}Se{sub 3} solar cells.« less

Coherent Charge Transport in Ballistic InSb Nanowire Josephson Junctions

PubMed Central

Li, S.; Kang, N.; Fan, D. X.; Wang, L. B.; Huang, Y. Q.; Caroff, P.; Xu, H. Q.

2016-01-01

Hybrid InSb nanowire-superconductor devices are promising for investigating Majorana modes and topological quantum computation in solid-state devices. An experimental realisation of ballistic, phase-coherent superconductor-nanowire hybrid devices is a necessary step towards engineering topological superconducting electronics. Here, we report on a low-temperature transport study of Josephson junction devices fabricated from InSb nanowires grown by molecular-beam epitaxy and provide a clear evidence for phase-coherent, ballistic charge transport through the nanowires in the junctions. We demonstrate that our devices show gate-tunable proximity-induced supercurrent and clear signatures of multiple Andreev reflections in the differential conductance, indicating phase-coherent transport within the junctions. We also observe periodic modulations of the critical current that can be associated with the Fabry-Pérot interference in the nanowires in the ballistic transport regime. Our work shows that the InSb nanowires grown by molecular-beam epitaxy are of excellent material quality and hybrid superconducting devices made from these nanowires are highly desirable for investigation of the novel physics in topological states of matter and for applications in topological quantum electronics. PMID:27102689

Dynamic Response of CoSb2O6 Trirutile-Type Oxides in a CO2 Atmosphere at Low-Temperatures

PubMed Central

Guillén-Bonilla, Alex; Rodríguez-Betancourtt, Verónica-María; Flores-Martínez, Martín; Blanco-Alonso, Oscar; Reyes-Gómez, Juan; Gildo-Ortiz, Lorenzo; Guillén-Bonilla, Héctor

2014-01-01

Experimental work on the synthesis of the CoSb2O6 oxide and its CO2 sensing properties is presented here. The oxide was synthesized by a microwave-assisted colloidal method in presence of ethylenediamine after calcination at 600 °C. This CoSb2O6 oxide crystallized in a tetragonal structure with cell parameters a = 4.6495 and c = 9.2763 Å, and space group P42/mnm. To prove its physical, chemical and sensing properties, the oxide was subjected to a series of tests: Raman spectroscopy, Scanning Electron Microscopy (SEM) and impedance (Z) measurements. Microstructures, like columns, bars and hollow hemispheres, were observed. For the CO2 sensing test, a thick film of CoSb2O6 was used, measuring the impedance variations on the presence of air/CO2 flows (0.100 sccm/0.100 sccm) using AC (alternating current) signals in the frequency-range 0.1–100 kHz and low relative temperatures (250 and 300 °C). The CO2 sensing results were quite good. PMID:25162232

Enhanced stability of Bi-doped Ge2Sb2Te5 amorphous films

NASA Astrophysics Data System (ADS)

Dyussembayev, S.; Prikhodko, O.; Tsendin, K.; Timoshenkov, S.; Korobova, N.

2014-09-01

Although, several reviews have appeared on various physical properties and applications of chalcogenide glasses, there is no thorough study of local atomic structure and its modification for eutectic Ge-Sb-Te alloys doped with Bi. Ge2Sb2Te5 pure and Bi-doped films were deposited by ion-plasma sputtering method of synthesized GTS material on Si (100) and glass substrates coated with a conductive Al layer which was used as a bottom electrode. Current-voltage characteristics of different points of the same samples have been measured. Random distribution of inclusions within the sample made it possible to investigate the dependence of switching and memory effects on the phase composition at a constant value of other parameters. Measurements in the current controlled mode clearly showed that the memory state formation voltage does not depend on current in a wide range. Results indicate that the development of imaging technologies phase memory cells need to pay special attention to the conditions of Ge-Sb-Te film preparation. To increase the number of cycles "write - erase" should be additional prolonged annealing of the synthesized films.

Formation of protein sub-visible particles during vacuum degassing of etanercept solutions.

PubMed

Wang, Haibin; Zheng, Hong-Jian; Wang, Zhao; Bai, Hua; Carpenter, John F; Chen, Shuqing; Fang, Wei-Jie

2014-05-01

The main purpose of this manuscript is to describe a phenomenon in which vacuum degassing a reconstituted freeze-dried fusion protein etanercept formulation caused a significant amount of protein sub-visible particles (SbVP). Physical stability of etanercept was monitored by micro-flow imaging (MFI), dynamic light scattering (DLS), size-exclusion high pressure liquid chromatography (SE-HPLC) and far- and near-ultraviolet circular dichroism (far- and near-UV CD). One potential explanation of this phenomenon is that bubble collapses when the vacuum is applied, leads to substantial heat formation, and ultimately free radical formation. Subsequently, the effect of a free-radical scavenger (ascorbic acid, AA) on SbVP formation was also evaluated. Degassing of etanercept solution by applying vacuum caused substantial increase of SbVP, as detected by MFI and DLS. However, traditional techniques such as SE-HPLC could not detect any change. The addition of free-radical scavenger had minimal effect on SbVP formation, therefore the formation of free radicals was probably not the main cause for this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigating RAS Signaling in Cancer | Office of Cancer Clinical Proteomics Research

Cancer.gov

CPTAC expertise has been charged to develop RAS specific targeted proteomic assays to study the important pathways of human cancer. The oncogene RAS is linked to 30 percent of human cancers, but the search for a targeted therapy for RAS has remained elusive. To advance our understanding of this oncogene and to develop improved targeted therapies against RAS pathway, the National Cancer Institute (NCI) has launched a RAS Initiative.

Inhibition of Ras for cancer treatment: the search continues

PubMed Central

Baines, Antonio T.; Xu, Dapeng; Der, Channing J.

2012-01-01

Background The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Discussion Despite intensive effort, to date no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Conclusions Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery. PMID:22004085

Wild-type H- and N-Ras promote mutant K-Ras driven tumorigenesis by modulating the DNA damage response

PubMed Central

Grabocka, Elda; Pylayeva-Gupta, Yuliya; Jones, Mathew JK; Lubkov, Veronica; Yemanaberhan, Eyoel; Taylor, Laura; Jeng, Hao Hsuan; Bar-Sagi, Dafna

2014-01-01

SUMMARY Mutations in KRAS are prevalent in human cancers and universally predictive of resistance to anti-cancer therapeutics. Although it is widely accepted that acquisition of an activating mutation endows RAS genes with functional autonomy, recent studies suggest that the wild-type forms of Ras may contribute to mutant Ras-driven tumorigenesis. Here we show that downregulation of wild-type H-Ras or N-Ras in mutant K-Ras cancer cells leads to hyperactivation of the Erk/p90RSK and PI3K/Akt pathways, and consequently, the phosphorylation of Chk1 at an inhibitory site, Ser 280. The resulting inhibition of ATR/Chk1 signaling abrogates the activation of the G2 DNA damage checkpoint and confers specific sensitization of mutant K-Ras cancer cells to DNA damage chemotherapeutic agents in vitro and in vivo. PMID:24525237

Electrostatic Interactions Positively Regulate K-Ras Nanocluster Formation and Function▿

PubMed Central

Plowman, Sarah J.; Ariotti, Nicholas; Goodall, Andrew; Parton, Robert G.; Hancock, John F.

2008-01-01

The organization of Ras proteins into plasma membrane nanoclusters is essential for high-fidelity signal transmission, but whether the nanoscale enviroments of different Ras nanoclusters regulate effector interactions is unknown. We show using high-resolution spatial mapping that Raf-1 is recruited to and retained in K-Ras-GTP nanoclusters. In contrast, Raf-1 recruited to the plasma membrane by H-Ras is not retained in H-Ras-GTP nanoclusters. Similarly, upon epidermal growth factor receptor activation, Raf-1 is preferentially recruited to K-Ras-GTP and not H-Ras-GTP nanoclusters. The formation of K-Ras-GTP nanoclusters is inhibited by phosphorylation of S181 in the C-terminal polybasic domain or enhanced by blocking S181 phosphorylation, with a concomitant reduction or increase in Raf-1 plasma membrane recruitment, respectively. Phosphorylation of S181 does not, however, regulate in vivo interactions with the nanocluster scaffold galectin-3 (Gal3), indicating separate roles for the polybasic domain and Gal3 in driving K-Ras nanocluster formation. Together, these data illustrate that Ras nanocluster composition regulates effector recruitment and highlight the importance of lipid/protein nanoscale environments to the activation of signaling cascades. PMID:18458061

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

PubMed

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

2009-12-01

High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

CHMP6 and VPS4A mediate recycling of Ras to the plasma membrane to promote growth factor signaling

PubMed Central

Zheng, Ze-Yi; Cheng, Chiang-Min; Fu, Xin-Rong; Chen, Liuh-Yow; Xu, Lizhong; Terrillon, Sonia; Wong, Stephen T.; Bar-Sagi, Dafna; Songyang, Zhou; Chang, Eric C.

2011-01-01

While Ras is well-known to function on the plasma membrane (PM) to mediate growth factor signaling, increasing evidence suggests that Ras has complex roles in the cytoplasm. To uncover these roles, we screened a cDNA library and isolated H-Ras-binding proteins that also influence Ras functions. Many isolated proteins regulate trafficking involving endosomes; CHMP6/VPS20 and VPS4A, which interact with ESCRT-III, were chosen for further study. We showed that the binding is direct and occurs in endosomes. Furthermore, the binding is most efficient when H-Ras has a functional effector-binding-loop and is GTP-bound and ubiquitylated. CHMP6 and VPS4A also bound N-Ras, but not K-Ras. Repressing CHMP6 and VPS4A blocked Ras-induced transformation, which correlated with inefficient Ras localization to the PM as measured by cell fractionation and photobleaching. Moreover, silencing CHMP6 and VPS4A also blocked EGFR recycling. These data suggest that Ras interacts with key ESCRT-III components to promote recycling of itself and EGFR back to the PM to create a positive feedback loop to enhance growth factor signaling. PMID:22231449

Inhibitors of Ras-SOS Interactions.

PubMed

Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov, Ruth

2016-04-19

Activating Ras mutations are found in about 30 % of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still 'undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose "pathway drug cocktails", that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Graded inhibition of oncogenic Ras-signaling by multivalent Ras-binding domains

PubMed Central

2014-01-01

Background Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound and an active, GTP-bound state. Aberrant Ras activity as a result of oncogenic mutations causes de novo cell transformation and promotes tumor growth and progression. Results Here, we describe a novel strategy to block deregulated Ras activity by means of oligomerized cognate protein modules derived from the Ras-binding domain of c-Raf (RBD), which we named MSOR for multivalent scavengers of oncogenic Ras. The introduction of well-characterized mutations into RBD was used to adjust the affinity and hence the blocking potency of MSOR towards activated Ras. MSOR inhibited several oncogenic Ras-stimulated processes including downstream activation of Erk1/2, induction of matrix-degrading enzymes, cell motility and invasiveness in a graded fashion depending on the oligomerization grade and the nature of the individual RBD-modules. The amenability to accurate experimental regulation was further improved by engineering an inducible MSOR-expression system to render the reversal of oncogenic Ras effects controllable. Conclusion MSOR represent a new tool for the experimental and possibly therapeutic selective blockade of oncogenic Ras signals. PMID:24383791

Resistance and resilience of small-scale recirculating aquaculture systems (RAS) with or without algae to pH perturbation

PubMed Central

Giatsis, Christos; Md Yusoff, Fatimah; Verreth, Johan; Verdegem, Marc

2018-01-01

The experimental set-up of this study mimicked recirculating aquaculture systems (RAS) where water quality parameters such as dissolved oxygen, pH, temperature, and turbidity were controlled and wastes produced by fish and feeding were converted to inorganic forms. A key process in the RAS was the conversion of ammonia to nitrite and nitrite to nitrate through nitrification. It was hypothesized that algae inclusion in RAS would improve the ammonia removal from the water; thereby improving RAS water quality and stability. To test this hypothesis, the stability of the microbiota community composition in a freshwater RAS with (RAS+A) or without algae (RAS-A) was challenged by introducing an acute pH drop (from pH 7 to 4 during three hours) to the system. Stigeoclonium nanum, a periphytic freshwater microalga was used in this study. No significant effect of the algae presence was found on the resistance to the acute pH drop on ammonia conversion to nitrite and nitrite conversion to nitrate. Also the resilience of the ammonia conversion to the pH drop disruption was not affected by the addition of algae. This could be due to the low biomass of algae achieved in the RAS. However, with regard to the conversion step of nitrite to nitrate, RAS+A was significantly more resilient than RAS-A. In terms of overall bacterial communities, the composition and predictive function of the bacterial communities was significantly different between RAS+A and RAS-A. PMID:29659617

RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells.

PubMed

Han, Shujie; Knoepp, Stewart M; Hallman, Mark A; Meier, Kathryn E

2007-01-01

The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to the tumor promoter phorbol 12-myristate 13-acetate (PMA). In sensitive EL4 cells, PMA causes robust Erk mitogen-activated protein kinase activation that results in growth arrest. In resistant cells, PMA induces minimal Erk activation, without growth arrest. PMA stimulates IL-2 production in sensitive, but not resistant, cells. The role of RasGRP1, a PMA-activated guanine nucleotide exchange factor for Ras, in EL4 phenotype was examined. Endogenous RasGRP1 protein is expressed at much higher levels in sensitive than in resistant cells. PMA-induced Ras activation is observed in sensitive cells but not in resistant cells lacking Ras-GRP1. PMA induces down-regulation of RasGRP1 protein in sensitive cells but increases RasGRP1 in resistant cells. Transfection of RasGRP1 into resistant cells enhances PMA-induced Erk activation. In the reverse experiment, introduction of small interfering RNA (siRNA) for RasGRP1 suppresses PMA-induced Ras and Erk activations in sensitive cells. Sensitive cells incubated with siRNA for RasGRP1 exhibit the PMA-resistant phenotype, in that they are able to proliferate in the presence of PMA and do not secrete IL-2 when stimulated with PMA. These studies indicate that the PMA-sensitive phenotype, as previously defined for the EL4 cell line, is conferred by endogenous expression of RasGRP1 protein.

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

PubMed Central

Hocker, Harrison J.; Cho, Kwang-Jin; Chen, Chung-Ying K.; Rambahal, Nandini; Sagineedu, Sreenivasa Rao; Shaari, Khozirah; Stanslas, Johnson; Hancock, John F.; Gorfe, Alemayehu A.

2013-01-01

Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)—a bicyclic diterpenoid lactone isolated from Andrographis paniculata—and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP–GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP–GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras. PMID:23737504

Blood-based detection of RAS mutations to guide anti-EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue-based RAS testing.

PubMed

Schmiegel, Wolff; Scott, Rodney J; Dooley, Susan; Lewis, Wendy; Meldrum, Cliff J; Pockney, Peter; Draganic, Brian; Smith, Steve; Hewitt, Chelsee; Philimore, Hazel; Lucas, Amanda; Shi, Elva; Namdarian, Kateh; Chan, Timmy; Acosta, Danilo; Ping-Chang, Su; Tannapfel, Andrea; Reinacher-Schick, Anke; Uhl, Waldemar; Teschendorf, Christian; Wolters, Heiner; Stern, Josef; Viebahn, Richard; Friess, Helmut; Janssen, Klaus-Peter; Nitsche, Ulrich; Slotta-Huspenina, Julia; Pohl, Michael; Vangala, Deepak; Baraniskin, Alexander; Dockhorn-Dworniczak, Barbara; Hegewisch-Becker, Susanne; Ronga, Philippe; Edelstein, Daniel L; Jones, Frederick S; Hahn, Stephan; Fox, Stephen B

2017-02-01

An accurate blood-based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti-EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood-based RAS mutation testing is a viable alternative to standard-of-care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin-fixed paraffin-embedded) tumor samples. Discordant tissue RAS results were re-examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Hemodynamic responses to acute and gradual renal artery stenosis in pigs.

PubMed

Rognant, Nicolas; Rouvière, Olivier; Janier, Marc; Lê, Quoc Hung; Barthez, Paul; Laville, Maurice; Juillard, Laurent

2010-11-01

Reduction of renal blood flow (RBF) due to a renal artery stenosis (RAS) can lead to renal ischemia and atrophy. However in pigs, there are no data describing the relationship between the degree of RAS, the reduction of RBF, and the increase of systemic plasma renin activity (PRA). Therefore, we conducted a study in order to measure the effect of acute and gradual RAS on RBF, mean arterial pressure (MAP), and systemic PRA in pigs. RAS was induced experimentally in six pigs using an occluder placed around the renal artery downstream of an ultrasound flow probe. The vascular occluder was inflated gradually to reduce RBF. At each inflation step, percentage of RAS was measured by digital subtraction angiography (DSA) with simultaneous measurements of RBF, MAP, and PRA. Data were normalized to baseline values obtained before RAS induction. Piecewise regression analysis was performed between percentage of RAS and relative RBF, MAP, and PRA, respectively. In all pigs, the relationship between the degree of RAS and RBF was similar. RBF decreased over a threshold of 42% of RAS, with a rapid drop in RBF when RAS reached 70%. PRA increased dramatically over a threshold of 58% of RAS (+1,300% before occlusion). MAP increased slightly (+15% before occlusion) without identifiable threshold. This study emphasizes that the relation between the degree of RAS and RBF and systemic PRA is not linear and that a high degree of RAS must be reached before the occurrence of significant hemodynamic and humoral effects.

Superelectrophilic tetrakis(carbonyl)palladium(II)- and -platinum(II) undecafluorodiantimonate(V), [Pd(CO)4][Sb(2)F(11)]2 and [Pt(CO)4][Sb(2)F(11)]2: syntheses, physical and spectroscopic properties, their crystal, molecular, and extended structures, and density functional calculations: an experimental, computational, and comparative study .

PubMed

Willner, H; Bodenbinder, M; Bröchler, R; Hwang, G; Rettig, S J; Trotter, J; von Ahsen, B; Westphal, U; Jonas, V; Thiel, W; Aubke, F

2001-01-31

The salts [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, are prepared by reductive carbonylation of Pd[Pd(SO(3)F)(6)], Pt(SO(3)F)(4) or PtF(6) in liquid SbF(5), or HF-SbF(5). The resulting moisture-sensitive, colorless solids are thermally stable up to 140 degrees C (M = Pd) or 200 degrees C (M = Pt). Their thermal decompositions are studied by differential scanning calorimetry (DSC). Single crystals of both salts are suitable for an X-ray diffraction study at 180 K. Both isostructural salts crystallize in the monoclinic space group P2(1)/c (No. 14). The unit cell volume of [Pt(CO)(4)][Sb(2)F(11)](2) is smaller than that of [Pd(CO)(4)][Sb(2)F(11)](2) by about 0.4%. The cations [M(CO)(4)](2+), M = Pd, Pt, are square planar with only very slight angular and out-of-plane deviations from D(4)(h)() symmetry. The interatomic distances and bond angles for both cations are essentially identical. The [Sb(2)F(11)](-) anions in [M(CO)(4)][Sb(2)F(11)](2,) M = Pd, Pt, are not symmetry-related, and both pairs differ in their Sb-F-Sb bridge angles and their dihedral angles. There are in each salt four to five secondary interionic C- -F contacts per CO group. Of these, two contacts per CO group are significantly shorter than the sum of the van der Waals radii by 0.58 - 0.37 A. In addition, structural, and spectroscopic details of recently synthesized [Rh(CO)(4)][Al(2)Cl(7)] are reported. The cations [Rh(CO)(4)](+) and [M(CO)(4)](2+), M = Pd, Pt, are characterized by IR and Raman spectroscopy. Of the 16 vibrational modes (13 observable, 3 inactive) 10 (Pd, Pt) or 9 (Rh), respectively, are found experimentally. The vibrational assignments are supported by DFT calculations, which provide in addition to band positions also intensities of IR bands and Raman signals as well as internal force constants for the cations. (13)C NMR measurements complete the characterization of the square planar metal carbonyl cations. The extensive characterization of [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, reported here, allows a comparison to linear and octahedral [M(CO)(n)()][Sb(2)F(11)](2) salts [M = Hg (n = 2); Fe, Ru, Os (n = 6)] and their derivatives, which permit a deeper understanding of M-CO bonding in the solid state for superelectrophilic cations with [Sb(2)F(11)](-) or [SbF(6)](-) as anions.

Synthesis, crystal structures, and physical properties of the new Zintl phases A{sub 21}Zn{sub 4}Pn{sub 18} (A=Ca, Eu; Pn=As, Sb)—Versatile arrangements of [ZnPn{sub 4}] tetrahedra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suen, Nian-Tzu; Wang, Yi; Bobev, Svilen, E-mail: bobev@udel.edu

Four new Zintl phases, Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18} and Eu{sub 21}Zn{sub 4}Sb{sub 18} have been synthesized by metal flux reactions. Their structures have been established from single-crystal X-ray diffraction. Despite the similar chemical makeup and the identical formulae, the structures of the four compounds are not the same—Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18} and Eu{sub 21}Zn{sub 4}As{sub 18} crystallize in the monoclinic space group C2/m (No. 12, Z=4) with the β-Ca{sub 21}Mn{sub 4}Sb{sub 18} structure type, while Eu{sub 21}Zn{sub 4}Sb{sub 18} adopts the Ba{sub 21}Cd{sub 4}Sb{sub 18} structure type withmore » the orthorhombic space group Cmce (No. 64, Z=8). Both structures are based on ZnAs{sub 4} or ZnSb{sub 4} tetrahedra, linked in slightly different ways, and Ca{sup 2+} and Eu{sup 2+} cations that fill the space between them. The structural relationships between the title compounds and other known ternary phases with intricate structures are discussed. Electrical resistivity measurement on single-crystalline Eu{sub 21}Zn{sub 4}Sb{sub 18} suggests an intrinsic semiconductor behavior with a band gap of ca. 0.2 eV. The temperature dependent DC magnetization measurement on the same material indicates Curie–Weiss paramagnetism in the high-temperature regime, and a spontaneous antiferromagnetic ordering below 8 K. The calculated effective moments of Eu confirm the divalent Eu{sup 2+} ground state, as expected from the Zintl–Klemm concept. - Graphical abstract: The four new Zintl phases—Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18}, and Eu{sub 21}Zn{sub 4}Sb{sub 18}—crystallize in two structure types, showing the versatility in the arrangements of ZnAs{sub 4} and ZnSb{sub 4} tetrahedra. - Highlights: • Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18}, and Eu{sub 21}Zn{sub 4}Sb{sub 18} are new compounds in the respective ternary phase diagrams. • They form with structure types, showing the versatility in the arrangements of ZnAs{sub 4} and ZnSb{sub 4} tetrahedra. • For both structures, the valence electron count follows the Zintl–Klemm rules.« less

The RAS Initiative

Cancer.gov

NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

K-ras p21 expression and activity in lung and lung tumors.

PubMed

Ramakrishna, G; Sithanandam, G; Cheng, R Y; Fornwald, L W; Smith, G T; Diwan, B A; Anderson, L M

2000-12-01

Although K-ras is mutated in many human and mouse lung adenocarcinomas, the function of K-ras p21 in lung is not known. We sought evidence for the prevalent hypothesis that K-ras p21 activates raf, which in turn passes the signal through the extracellular signal regulated kinases (Erks) to stimulate cell division, and that this pathway is upregulated when K-ras is mutated. Results from both mouse lung tumors and immortalized cultured E10 and C10 lung type II cells failed to substantiate this hypothesis. Lung tumors did not have more total K-ras p21 or K-ras p21 GTP than normal lung tissue, nor were high levels of these proteins found in tumors with mutant K-ras. Activated K-ras p21-GTP levels did not correlate with proliferating cell nuclear antigen. Special features of tumors with mutant K-ras included small size of carcinomas compared with carcinomas lacking this mutation, and correlation of proliferating cell nuclear antigen with raf-1. In nontransformed type II cells in culture, both total and activated K-ras p21 increased markedly at confluence but not after serum stimulation, whereas both Erk1/2 and the protein kinase Akt were rapidly activated by the serum treatment. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of K-ras mRNA indicated an increase in confluent and especially in postconfluent cells. Together the findings indicate that normal K-ras p21 activity is associated with growth arrest of lung type II cells, and that the exact contribution of mutated K-ras p21 to tumor development remains to be discovered.

Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord blood CD34 cells.

PubMed

Ge, Y; Li, Z H; Marshall, M S; Broxmeyer, H E; Lu, L

1998-06-01

To investigate the role of the ras gene in erythroid differentiation, a human erythroleukemic cell line, TF1, was transduced with a selectable retroviral vector carrying a mammalian wild type H-ras gene or a cytoplasmic dominant negative RAS1 gene. Transduction of TF1 cells with the wild type H-ras gene resulted in changes of cell types and up-regulation of erythroid-specific gene expression similar to that seen in differentiating erythroid cells. The number of red blood cell containing colonies derived from TF1 cells transduced with wild type H-ras cDNA was significantly increased and the cells in the colonies were more hemoglobinized as estimated by a deeper red color compared to those colony cells from mock or dominant negative RAS1 gene transduced TF1 cells, suggesting increased erythroid differentiation of TF1 cells after transduction of wild type H-ras in vitro. The mRNA levels of beta- and gamma-, but not alpha-, globin genes were significantly higher in H-ras transduced TF1 cells than those in TF1 cells transduced with mock or dominant negative RAS1 gene. Moreover, a 4kb pre-mRNA of the Erythropoietin receptor (EpoR) was highly expressed only in H-ras transduced TF1 cells. Additionally, human umbilical cord blood (CB) CD34 cells which are highly enriched for hematopoietic stem/progenitor cells were transduced with the same retroviral vectors to evaluate in normal primary cells the activities of H-ras in erythroid differentiation. Increased numbers of erythroid cell containing colonies (BFU-E and CFU-GEMM) were observed in CD34 cells transduced with the H-ras cDNA, compared to that from mock transduced cells. These data suggest a possible role for ras in erythroid differentiation.

siRNA blocking the RAS signalling pathway and inhibits the growth of oesophageal squamous cell carcinoma in nude mice.

PubMed

Wang, Xinjie; Zheng, Yuling; Fan, Qingxia; Zhang, Xudong; Shi, Yonggang

2014-12-01

The aim of this study was to study RAS-siRNA blocking RAS pathway and suppressing cell growth in human oesophageal squamous cell carcinoma in nude mice. The methods in this study was to construct RAS-siRNA expression vector, establish 40 oesophageal squamous cell carcinoma xenograft animal models and divided them into five groups: control group, siRNA control group, RAS-siRNA group, paclitaxel group and RAS-siRNA and paclitaxel group. We observed tumour growth in nude mice, studied histology by HE staining, tumour growth inhibition by TUNEL assay and detected the RAS, MAPK and cyclin D1 protein expression by immunohistochemistry and western blot. We have obtained the following results: (i) successfully established animal models; (ii) nude mice in each group after treatment inhibited tumour volume was significantly reduced compared with the control group (p < 0.05); (iii) compared with the control group, the number of apoptotic cells were significantly increased in the siRNA control group and the RAS-siRNA group, and the number of apoptosis cells in the paclitaxel and RAS-siRNA group is significantly most than the paclitaxel group and RAS-siRNA group (p < 0.05); and (iv) after treatment, RAS, MAPK and cyclin D1 expression in five groups was decreasing gradually. After adding paclitaxel, the protein expression in the paclitaxel and RAS-siRNA group was significantly lower than that of paclitaxel group, negative control and paclitaxel group (p < 0.05). We therefore conclude that RAS-siRNA can block the RAS signal transduction pathway, reduce the activity of tumour cells, arrest tumour cell cycle, promote apoptosis, inhibit cell proliferation and increase tumour cell sensitivity to chemotherapeutic drugs. Copyright © 2014 John Wiley & Sons, Ltd.

Mucosal and salivary microbiota associated with recurrent aphthous stomatitis.

PubMed

Kim, Yun-Ji; Choi, Yun Sik; Baek, Keum Jin; Yoon, Seok-Hwan; Park, Hee Kyung; Choi, Youngnim

2016-04-01

Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder of unclear etiopathogenesis. Although recent studies of the oral microbiota by high-throughput sequencing of 16S rRNA genes have suggested that imbalances in the oral microbiota may contribute to the etiopathogenesis of RAS, no specific bacterial species associated with RAS have been identified. The present study aimed to characterize the microbiota in the oral mucosa and saliva of RAS patients in comparison with control subjects at the species level. The bacterial communities of the oral mucosa and saliva from RAS patients with active lesions (RAS, n = 18 for mucosa and n = 8 for saliva) and control subjects (n = 18 for mucosa and n = 7 for saliva) were analyzed by pyrosequencing of the 16S rRNA genes. There were no significant differences in the alpha diversity between the controls and the RAS, but the mucosal microbiota of the RAS patients showed increased inter-subject variability. A comparison of the relative abundance of each taxon revealed decreases in the members of healthy core microbiota but increases of rare species in the mucosal and salivary microbiota of RAS patients. Particularly, decreased Streptococcus salivarius and increased Acinetobacter johnsonii in the mucosa were associated with RAS risk. A dysbiosis index, which was developed using the relative abundance of A. johnsonii and S. salivarius and the regression coefficients, correctly predicted 83 % of the total cases for the absence or presence of RAS. Interestingly, A. johnsonii substantially inhibited the proliferation of gingival epithelial cells and showed greater cytotoxicity against the gingival epithelial cells than S. salivarius. RAS is associated with dysbiosis of the mucosal and salivary microbiota, and two species associated with RAS have been identified. This knowledge may provide a diagnostic tool and new targets for therapeutics for RAS.

Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells.

PubMed

Stanhill, A; Levin, V; Hendel, A; Shachar, I; Kazanov, D; Arber, N; Kaminski, N; Engelberg, D

2006-03-09

Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

The Significance of Ras Activity in Pancreatic Cancer Initiation.

PubMed

Logsdon, Craig D; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Ras(mt). Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras(mt) is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Ras(mt) activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras(mt). Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras(mt) activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease.

Exploiting the bad eating habits of Ras-driven cancers.

PubMed

White, Eileen

2013-10-01

Oncogenic Ras promotes glucose fermentation and glutamine use to supply central carbon metabolism, but how and why have only emerged recently. Ras-mediated metabolic reprogramming generates building blocks for growth and promotes antioxidant defense. To fuel metabolic pathways, Ras scavenges extracellular proteins and lipids. To bolster metabolism and mitigate stress, Ras activates cellular self-cannibalization and recycling of proteins and organelles by autophagy. Targeting these distinct features of Ras-driven cancers provides novel approaches to cancer therapy.

Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.

PubMed

Yan, Hua; Jahanshahi, Maryam; Horvath, Elizabeth A; Liu, Hsiu-Yu; Pfleger, Cathie M

2010-08-10

The Ras signaling pathway allows cells to translate external cues into diverse biological responses. Depending on context and the threshold reached, Ras signaling can promote growth, proliferation, differentiation, or cell survival. Failure to maintain precise control of Ras can have adverse physiological consequences. Indeed, excess Ras signaling disrupts developmental patterning and causes developmental disorders [1, 2], and in mature tissues, it can lead to cancer [3-5]. We identify Rabex-5 as a new component of Ras signaling crucial for achieving proper pathway outputs in multiple contexts in vivo. We show that Drosophila Rabex-5 restricts Ras signaling to establish organism size, wing vein pattern, and eye versus antennal fate. Rabex-5 has both Rab5 guanine nucleotide exchange factor (GEF) activity that regulates endocytic trafficking [6] and ubiquitin ligase activity [7, 8]. Surprisingly, overexpression studies demonstrate that Rabex-5 ubiquitin ligase activity, not its Rab5 GEF activity, is required to restrict wing vein specification and to suppress the eye phenotypes of oncogenic Ras expression. Furthermore, genetic interaction experiments indicate that Rabex-5 acts at the step of Ras, and tissue culture studies show that Rabex-5 promotes Ras ubiquitination. Together, these findings reveal a new mechanism for attenuating Ras signaling in vivo and suggest an important role for Rabex-5-mediated Ras ubiquitination in pathway homeostasis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The assessment of weight status in children and young people attending a spina bifida outpatient clinic: a retrospective medical record review

PubMed Central

Swift, Judy Anne; Yung, Emily; Lyons, Julia; Church, Paige

2013-01-01

Purpose Children with disabilities are two to three times more likely to become overweight or obese than typically developing children. Children with spina bifida (SB) are at particular risk, yet obesity prevalence and weight management with this population are under-researched. This retrospective chart review explored how weight is assessed and discussed in a children’s SB outpatient clinic. Method Height/weight data were extracted from records of children aged 2–18 with a diagnosis of SB attending an outpatient clinic at least once between June 2009–2011. Body mass index was calculated and classified using Centers for Disease Control and Prevention cut-offs. Notes around weight, diet and physical/sedentary activities were transcribed verbatim and analysed using descriptive thematic analysis. Results Of 180 eligible patients identified, only 63 records had sufficient data to calculate BMI; 15 patients were overweight (23.81%) and 11 obese (17.46%). Weight and physical activity discussions were typically related to function (e.g. mobility, pain). Diet discussions focused on bowel and bladder function and dietary challenges. Conclusions Anthropometrics were infrequently recorded, leaving an incomplete picture of weight status in children with SB and suggesting that weight is not prioritised. Bowel/bladder function was highlighted over other benefits of a healthy body weight, indicating that health promotion opportunities are being missed. Implications for Rehabilitation It is important to assess, categorise and record anthropometric data for children and youth with spina bifida as they may be at particular risk of excess weight. Information around weight categorisation should be discussed openly and non-judgmentally with children and their families. Health promotion opportunities may be missed by focusing solely on symptom management or function. Healthcare professionals should emphasise the broad benefits of healthy eating and physical activity, offering strategies to enable the child to incorporate healthy lifestyle behaviours appropriate to their level of ability. PMID:23510013

The assessment of weight status in children and young people attending a spina bifida outpatient clinic: a retrospective medical record review.

PubMed

McPherson, Amy C; Swift, Judy Anne; Yung, Emily; Lyons, Julia; Church, Paige

2013-01-01

Children with disabilities are two to three times more likely to become overweight or obese than typically developing children. Children with spina bifida (SB) are at particular risk, yet obesity prevalence and weight management with this population are under-researched. This retrospective chart review explored how weight is assessed and discussed in a children's SB outpatient clinic. Height/weight data were extracted from records of children aged 2-18 with a diagnosis of SB attending an outpatient clinic at least once between June 2009-2011. Body mass index was calculated and classified using Centers for Disease Control and Prevention cut-offs. Notes around weight, diet and physical/sedentary activities were transcribed verbatim and analysed using descriptive thematic analysis. Of 180 eligible patients identified, only 63 records had sufficient data to calculate BMI; 15 patients were overweight (23.81%) and 11 obese (17.46%). Weight and physical activity discussions were typically related to function (e.g. mobility, pain). Diet discussions focused on bowel and bladder function and dietary challenges. Anthropometrics were infrequently recorded, leaving an incomplete picture of weight status in children with SB and suggesting that weight is not prioritised. Bowel/bladder function was highlighted over other benefits of a healthy body weight, indicating that health promotion opportunities are being missed. Implications for Rehabilitation It is important to assess, categorise and record anthropometric data for children and youth with spina bifida as they may be at particular risk of excess weight. Information around weight categorisation should be discussed openly and non-judgmentally with children and their families. Health promotion opportunities may be missed by focusing solely on symptom management or function. Healthcare professionals should emphasise the broad benefits of healthy eating and physical activity, offering strategies to enable the child to incorporate healthy lifestyle behaviours appropriate to their level of ability.

Molecular pathways: targeting RAC-p21-activated serine-threonine kinase signaling in RAS-driven cancers.

PubMed

Baker, Nicole M; Yee Chow, Hoi; Chernoff, Jonathan; Der, Channing J

2014-09-15

Cancers driven by oncogenic Ras proteins encompass some of the most deadly human cancer types, and there is a pressing need to develop therapies for these diseases. Although recent studies suggest that mutant Ras proteins may yet be druggable, the most promising and advanced efforts involve inhibitors of Ras effector signaling. Most efforts to target Ras signaling have been aimed at the ERK mitogen-activated protein kinase and the phosphoinositide 3-kinase signaling networks. However, to date, no inhibitors of these Ras effector pathways have been effective against RAS-mutant cancers. This ineffectiveness is due, in part, to the involvement of additional effectors in Ras-dependent cancer growth, such as the Rac small GTPase and the p21-activated serine-threonine kinases (PAK). PAK proteins are involved in many survival, cell motility, and proliferative pathways in the cell and may present a viable new target in Ras-driven cancers. In this review, we address the role and therapeutic potential of Rac and group I PAK proteins in driving mutant Ras cancers. ©2014 American Association for Cancer Research.

Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling

PubMed Central

Ariotti, Nicholas; Fernández-Rojo, Manuel A.; Zhou, Yong; Hill, Michelle M.; Rodkey, Travis L.; Inder, Kerry L.; Tanner, Lukas B.; Wenk, Markus R.

2014-01-01

The molecular mechanisms whereby caveolae exert control over cellular signaling have to date remained elusive. We have therefore explored the role caveolae play in modulating Ras signaling. Lipidomic and gene array analyses revealed that caveolin-1 (CAV1) deficiency results in altered cellular lipid composition, and plasma membrane (PM) phosphatidylserine distribution. These changes correlated with increased K-Ras expression and extensive isoform-specific perturbation of Ras spatial organization: in CAV1-deficient cells K-RasG12V nanoclustering and MAPK activation were enhanced, whereas GTP-dependent lateral segregation of H-Ras was abolished resulting in compromised signal output from H-RasG12V nanoclusters. These changes in Ras nanoclustering were phenocopied by the down-regulation of Cavin1, another crucial caveolar structural component, and by acute loss of caveolae in response to increased osmotic pressure. Thus, we postulate that caveolae remotely regulate Ras nanoclustering and signal transduction by controlling PM organization. Similarly, caveolae transduce mechanical stress into PM lipid alterations that, in turn, modulate Ras PM organization. PMID:24567358

Nitrative and oxidative DNA damage caused by K-ras mutation in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohnishi, Shiho; Saito, Hiromitsu; Suzuki, Noboru

2011-09-23

Highlights: {yields} Mutated K-ras in transgenic mice caused nitrative DNA damage, 8-nitroguanine. {yields} The mutagenic 8-nitroguanine seemed to be generated by iNOS via Ras-MAPK signal. {yields} Mutated K-ras produces additional mutagenic lesions, as a new oncogenic role. -- Abstract: Ras mutation is important for carcinogenesis. Carcinogenesis consists of multi-step process with mutations in several genes. We investigated the role of DNA damage in carcinogenesis initiated by K-ras mutation, using conditional transgenic mice. Immunohistochemical analysis revealed that mutagenic 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were apparently formed in adenocarcinoma caused by mutated K-ras. 8-Nitroguanine was co-localized with iNOS, eNOS, NF-{kappa}B, IKK, MAPK, MEK,more » and mutated K-ras, suggesting that oncogenic K-ras causes additional DNA damage via signaling pathway involving these molecules. It is noteworthy that K-ras mutation mediates not only cell over-proliferation but also the accumulation of mutagenic DNA lesions, leading to carcinogenesis.« less

A New Strategy to Control and Eradicate “Undruggable” Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology

PubMed Central

Lee, Michael P.; Lee, Caroline Dasom; Lafever, Alex C.; Svyatova, Elizaveta; Kanda, Kevin; Collier, Amber L.; Siewertsz van Reesema, Lauren L.; Tang-Tan, Angela M.; Zheleva, Vasilena; Bwayi, Monicah N.; Bian, Minglei; Schmidt, Rebecca L.; Petersen, Gloria M.

2018-01-01

Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely “undruggable”. Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper RAS signaling. Guided by molecular insights and core principles obtained from developmental and evolutionary biology, we propose an anti-SIAH-centered anti-K-RAS strategy as a logical and alternative anticancer strategy to dampen uncontrolled K-RAS hyperactivation and halt tumor growth and metastasis in pancreatic cancer. The clinical utility of developing SIAH as both a tumor-specific and therapy-responsive biomarker, as well as a viable anti-K-RAS drug target, is logically simple and conceptually innovative. SIAH clearly constitutes a major tumor vulnerability and K-RAS signaling bottleneck in pancreatic ductal adenocarcinoma (PDAC). Given the high degree of evolutionary conservation in the K-RAS/SIAH signaling pathway, an anti-SIAH-based anti-PDAC therapy will synergize with covalent K-RAS inhibitors and direct K-RAS targeted initiatives to control and eradicate pancreatic cancer in the future. PMID:29757973

Ras-related tumorigenesis is suppressed by BNIP3-mediated autophagy through inhibition of cell proliferation.

PubMed

Wu, Shan-Ying; Lan, Sheng-Hui; Cheng, Da-En; Chen, Wei-Kai; Shen, Cheng-Huang; Lee, Ying-Ray; Zuchini, Roberto; Liu, Hsiao-Sheng

2011-12-01

Autophagy plays diverse roles in Ras-related tumorigenesis. H-ras(val12) induces autophagy through multiple signaling pathways including Raf-1/ERK pathway, and various ERK downstream molecules of autophagy have been reported. In this study, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) is identified as a downstream transducer of the Ras/Raf/ERK signaling pathway to induce autophagy. BNIP3 was upregulated by H-ras(val12) at the transcriptional level to compete with Beclin 1 for binding with Bcl-2. H-ras(val12)-induced autophagy suppresses cell proliferation demonstrated both in vitro and in vivo by expression of ectopic BNIP3, Atg5, or interference RNA of BNIP3 (siBNIP3) and Atg5 (shAtg5) using mouse NIH3T3 and embryo fibroblast cells. H-ras(val12) induces different autophagic responses depending on the duration of Ras overexpression. After a short time (48 hours) of Ras overexpression, autophagy inhibits cell proliferation. In contrast, a longer time (2 weeks) of Ras overexpression, cell proliferation was enhanced by autophagy. Furthermore, overexpression of mutant Ras, BNIP3, and LC3-II was detected in bladder cancer T24 cells and the tumor parts of 75% of bladder cancer specimens indicating a positive correlation between autophagy and tumorigenesis. Taken together, our mouse model demonstrates a balance between BNIP3-mediated autophagy and H-ras(val12)-induced tumor formation and reveals that H-ras(val12) induces autophagy in a BNIP3-dependent manner, and the threshold of autophagy plays a decisive role in H-ras(val12)-induced tumorigenesis. Our findings combined with others' reports suggest a new therapeutic strategy against Ras-related tumorigenesis by negative or positive regulation of autophagic activity, which is determined by the level of autophagy and tumor progression stages.

Inhibition of Fas (CD95) expression and Fas-mediated apoptosis by oncogenic Ras.

PubMed

Fenton, R G; Hixon, J A; Wright, P W; Brooks, A D; Sayers, T J

1998-08-01

The ras oncogene plays an important role in the multistep progression to cancer by activation of signal transduction pathways that contribute to aberrant growth regulation. Although many of these effects are cell autonomous, the ras oncogene also regulates the expression of genes that alter host/tumor interactions. We now extend the mechanisms through which ras promotes tumor survival by demonstrating that oncogenic Ras inhibits expression of the fas gene and renders Ras-transformed cells resistant to Fas-induced apoptosis. A panel of Ras-transformed clones exhibited a marked inhibition in fas mRNA and Fas cell surface expression as compared with untransformed parental cell lines. Fas expression was induced by culture in the presence of IFN-gamma + tumor necrosis factor alpha; however, the maximal level attained in Ras transformants was approximately 10-fold below the level of untransformed cells. Whereas untransformed cells were sensitive to apoptotic death induced by cross-linking surface Fas (especially after cytokine treatment), Ras-transformed cells were very resistant to Fas-induced death even under the most stringent assay conditions. To demonstrate that this resistance was mediated by oncogenic Ras and not secondary genetic events, pools of Ras-transformed cells were generated using a highly efficient retroviral transduction technique. Transformed pools were assayed 6 days after infection and demonstrated a marked decrease in fas gene expression and Fas-mediated apoptosis. Oncogenic Ras did not promote general resistance to apoptosis, because ectopic expression of a fas cDNA in Ras-transformed cells restored sensitivity to Fas-induced apoptosis. These data indicate that oncogenic Ras inhibits basal levels of expression of the fas gene, and although cytokine signal transduction pathways are functional in these cells, the level of surface Fas expression remains below the threshold required for induction of apoptosis. These data identify a mechanism by which Ras-transformed cells may escape from host-mediated immune destruction.

Association of physical activity and sedentary behavior with depression and anxiety symptoms during pregnancy in a multiethnic cohort of Asian women.

PubMed

Padmapriya, Natarajan; Bernard, Jonathan Y; Liang, Shen; Loy, See Ling; Shen, Zhe; Kwek, Kenneth; Godfrey, Keith M; Gluckman, Peter D; Chong, Yap-Seng; Saw, Seang Mei; Meaney, Michael J; Chen, Helen; Müller-Riemenschneider, Falk

2016-12-01

This study aimed to investigate associations of physical activity (PA) and sedentary behavior (SB) with depression and anxiety symptoms during pregnancy among Chinese, Malay, and Indian women. Women answered PA and SB (sitting time and television time) interview questions and self-completed the Edinburgh Postnatal Depression Scale (EPDS) and State-Trait Anxiety Inventory (STAI) questionnaires, at week 26-28 gestation. Sufficient levels of PA (≥600MET-minutes/week) and higher sitting time (≥7 h/day) were determined. Associations of PA and SB with probable antenatal depression (EPDS-score ≥15), higher state anxiety (score ≥42), and higher trait anxiety (score ≥43) were determined by logistic regression analysis. Among the 1144 pregnant women included in the study, 7.3, 22.5, and 23.6 % had probable antenatal depression, higher state anxiety, and higher trait anxiety symptoms, respectively. In the adjusted models, women with sufficient level of PA were less likely to have probable antenatal depression (OR 0.54, 95 % CI 0.31-0.94, p = 0.030) and higher trait anxiety symptoms (OR 0.68, 95 % CI 0.48-0.94, p = 0.022). PA was not associated with state anxiety symptoms. SB was not associated with any of the investigated outcomes. Sufficient PA was associated with a reduced likelihood of probable antenatal depression and trait anxiety symptoms. Further investigation of these findings is warranted to determine cause-effect relationships and identify potential preventive strategies.

Barriers and facilitators to young children's physical activity and sedentary behaviour: a systematic review and synthesis of qualitative literature

PubMed Central

Lakshman, R.; van Sluijs, E. M. F.

2017-01-01

Summary Positive activity behaviours (i.e. higher physical activity [PA]/lower sedentary behaviour [SB]) are beneficial from infancy, yet evidence suggests that young children (0‐ to 6‐year‐olds) are relatively inactive. To better understand the perceived influences on these behaviours and to aid intervention development, this paper systematically synthesizes the extensive qualitative literature regarding perceived barriers and facilitators to PA and SB in young children (0–6 years old). A search of eight electronic databases (July 2016) identified 43 papers for inclusion. Data extraction and evidence synthesis were conducted using thematic content analysis, underpinned by the socio‐ecological model (i.e. individual, interpersonal, community, organizational and policy levels). Parents, childcare providers and children perceived seven broad themes to be important for PA and SB, including the child; the home; out‐of‐home childcare; parent–childcare provider interactions; environmental factors; safety; and weather. Each theme mapped onto between one and five levels of the socio‐ecological model; barriers and facilitators at the interpersonal level (e.g. parents, care providers and family) were most frequently cited, reflecting the important (perceived) role adults/peers play in shaping young children's behaviours. We provide an overarching framework to explain PA and SB in early childhood. We also highlight where gaps in the current literature exist (e.g. from male carers; in developing countries; and barriers and facilitators in the environmental and policy domains) and where future quantitative work may focus to provide novel insights about children's activity behaviours (e.g. safety and weather). PMID:28589678

Ovarian expression of cellular Ki-ras p21 varies with physiological status.

PubMed Central

Palejwala, S; Goldsmith, L T

1992-01-01

To elucidate the potential role of the ras protooncogene proteins in a specific tissue, the present study determined the levels of individual c-ras-encoded p21 proteins in the rat ovary during various stages of physiological function. p21 protein was extracted from ovaries taken from immature normal female rats, mature nonpregnant animals in the metestrus stage of the estrus cycle, rats at various stages of pregnancy, and actively lactating animals. Levels of individual p21s were evaluated by immunoblot analysis with specific antibodies to the p21 proteins encoded by the Kirsten, Harvey, and neuroblastoma c-ras protooncogenes, c-Ki-ras, c-Ha-ras, and N-ras. Results showed that c-Ki-ras p21 is at its lowest level in the immature ovary and increases with development of the corpora lutea to its highest levels at day 16 of pregnancy, after which levels decline and then rise again during lactation. This pattern, which mimics that of circulating progesterone levels, suggests that ovarian c-Ki-ras p21 levels are regulated and that c-Ki-ras p21 plays a role in the differentiated function of the rat ovary, likely the luteal compartment. In contrast, levels of c-N-ras p21 did not appear to vary with changes in the physiological function of the ovary but appeared to be constitutive. A preferential role for the c-Ki-ras p21 may be due to the documented unique differences in the structure of the carboxyl terminus of this particular c-ras p21. Images PMID:1570348

Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation

PubMed Central

Bettoun, Audrey; Surdez, Didier; Vallerand, David; Gundogdu, Ramazan; Sharif, Ahmad A.D.; Gomez, Marta; Cascone, Ilaria; Meunier, Brigitte; White, Michael A.; Codogno, Patrice; Parrini, Maria Carla; Camonis, Jacques H.; Hergovich, Alexander

2016-01-01

Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells. PMID:27283898

New KRAS Antibodies Available | Office of Cancer Clinical Proteomics Research

Cancer.gov

Researchers estimate that approximately 30% of all human cancers are driven by RAS oncogenes. Mutated RAS genes are responsible for making RAS proteins that support cancer development. While anti-RAS therapies may have potential clinical benefit, researchers yet do not understand how the four RAS protein isoforms, KRAS4A, KRAS4B, HRAS, and NRAS, drive malignant phenotypes. Well-characterized and defined reagents like antibodies are central to reproducibility in biomedical research and necessary for future RAS studies.

Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation.

PubMed

Ni, Duan; Song, Kun; Zhang, Jian; Lu, Shaoyong

2017-10-26

Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras-mediated signaling pathway, but its efficacy is reduced by R135K mutation in H-Ras. However, the detailed mechanism is unresolved. Here, using molecular dynamics (MD) simulations and dynamic network analysis, we explored the molecular mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying allosteric network in H-Ras. MD simulations revealed that the overall structures of the two complexes did not change significantly, but the H-Ras-NS1 interface underwent significant conformational alteration in the mutant Binding free energy analysis showed that NS1 binding was unfavored after R135K mutation, which resulted in the unfavorable binding of NS1. Furthermore, the critical residues on H-Ras responsible for the loss of binding of NS1 were identified. Importantly, the allosteric networks for these important residues were revealed, which yielded a novel insight into the allosteric regulatory mechanism of H-Ras.

An orthosteric inhibitor of the RAS-SOS interaction.

PubMed

Nickerson, Seth; Joy, Stephen T; Arora, Paramjit S; Bar-Sagi, Dafna

2013-01-01

Rat sarcoma (RAS) proteins are signaling nodes that transduce extracellular cues into precise alterations in cellular physiology by engaging effector pathways. RAS signaling thus regulates diverse cell processes including proliferation, migration, differentiation, and survival. Owing to this central role in governing mitogenic signals, RAS pathway components are often dysregulated in human diseases. Targeted therapy of RAS pathways has generally not been successful, largely because of the robust biochemistry of the targets and their multifaceted network of molecular regulators. The rate-limiting step of RAS activation is Son of Sevenless (SOS)-mediated nucleotide exchange involving a single evolutionarily conserved catalytic helix from SOS. Structure function data of this mechanism provided a strong platform to design an SOS-derived, helically constrained peptide mimic as an inhibitor of the RAS-SOS interaction. In this chapter, we review RAS-SOS signaling dynamics and present evidence supporting the novel paradigm of inhibiting their interaction as a therapeutic strategy. We then describe a method of generating helically constrained peptide mimics of protein surfaces, which we have employed to inhibit the RAS-SOS active site interaction. The biochemical and functional properties of this SOS mimic support the premise that inhibition of RAS-nucleotide exchange can effectively block RAS activation and downstream signaling. © 2013 Elsevier Inc. All rights reserved.

R-Ras Contributes to LTP and Contextual Discrimination

PubMed Central

Darcy, Michael J.; Jin, Shan-Xue; Feig, Larry A.

2014-01-01

The ability to discriminate between closely related contexts is a specific form of hippocampal-dependent learning that may be impaired in certain neurodegenerative disorders such as Alzheimer's and Down Syndrome. However, signaling pathways regulating this form of learning are poorly understood. Previous studies have shown that the calcium-dependent exchange factor Ras-GRF1, an activator of Rac, Ras and R-Ras GTPases, is important for this form of learning and memory. Moreover, the ability to discriminate contexts was linked to the ability of Ras-GRF1 to promote high-frequency stimulation (HFS)-LTP via the activation of p38 Map kinase. Here, we show that R-Ras is involved in this form of learning by using virally-delivered miRNAs targeting R-Ras into the CA1 region of dorsal hippocampus and observing impaired contextual discrimination. Like the loss of GRF1, knockdown of R-Ras in the CA1 also impairs the induction of HFS-LTP and p38 Map kinase. Nevertheless, experiments indicate that this involvement of R-Ras in HFS-LTP that is required for contextual discrimination is independent of Ras-GRF1. Thus, R-Ras is a novel regulator of a form of hippocampal-dependent LTP as well as learning and memory that is affected in certain forms of neurodegenerative diseases. PMID:25043327

K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakamoto, Kotaro; Kamada, Yusuke; Sameshima, Tomoya

Amino-acid mutations of Gly{sup 12} (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH{sub 2}) as a consensus sequence. KRpep-2 showedmore » more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K{sub D} and IC{sub 50} values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH{sub 2}) that inhibited enzyme activity of K-Ras(G12D) with IC{sub 50} = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. - Highlights: • The first K-Ras(G12D)-selective inhibitory peptides were generated. • These peptides showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D) in compared to wild type K-Ras. • The peptide KRpep-2d suppressed downstream signal of K-Ras(G12D) and cell proliferations of cancer cell line A427.« less

Subcellular Distribution of S-Nitrosylated H-Ras in Differentiated and Undifferentiated PC12 Cells during Hypoxia.

PubMed

Barbakadze, Tamar; Goloshvili, Galina; Narmania, Nana; Zhuravliova, Elene; Mikeladze, David

2017-10-01

Hypoxia or exposure to excessive reactive oxygen or nitrogen species could induce S-nitrosylation of various target proteins, including GTPases of the Ras-superfamily. Under hypoxic conditions, the Ras-protein is translocated to the cytosol and interacts with the Golgi complex, endoplasmic reticulum, mitochondria. The mobility/translocation of Ras depend on the cells oxidative status. However, the importance of relocated Snitrosylated- H-Ras (NO-H-Ras) in proliferation/differentiation processes is not completely understood. We have determined the content of soluble- and membrane-bound-NO-HRas in differentiated (D) and undifferentiated (ND) rat pheochromocytoma (PC12) cells under hypoxic and normoxic conditions. In our experimental study, we analyzed NO-H-Ras levels under hypoxic/normoxic conditions in membrane and soluble fractions of ND and D PC12 cells with/without nitric oxide donor, sodium nitroprusside (SNP) treatment. Cells were analyzed by the S-nitrosylated kit, immunoprecipitation, and Western blot. We assessed the action of NO-H-Ras on oxidative metabolism of isolated mitochondria by determining mitochondrial hydrogen peroxide generation via the scopoletin oxidation method and ATPproduction as estimated by the luminometric method. Hypoxia did not influence nitrosylation of soluble H-Ras in ND PC12 cells. Under hypoxic conditions, the nitrosylation of soluble-H-Ras greatly decreased in D PC12 cells. SNP didn't change the levels of nitrosylation of soluble-H-Ras, in either hypoxic or normoxic conditions. On the other hand, hypoxia, per se, did not affect the nitrosylation of membrane-bound-H-Ras in D and ND PC12 cells. SNP-dependent nitrosylation of membrane-bound-H-Ras greatly increased in D PC12 cells. Both unmodified normal and mutated H-Ras enhanced the mitochondrial synthesis of ATP, whereas the stimulatory effects on ATP synthesis were eliminated after S-nitrosylation of H-Ras. According to the results, it may be proposed that hypoxia can decrease S-nitrosylation of soluble-H-Ras in D PC12 cells and abolish the inhibitory effect of NO-HRas in mitochondrial oxidative metabolism. Copyright© by Royan Institute. All rights reserved.

'Let's Move It' - a school-based multilevel intervention to increase physical activity and reduce sedentary behaviour among older adolescents in vocational secondary schools: a study protocol for a cluster-randomised trial.

PubMed

Hankonen, Nelli; Heino, Matti T J; Araujo-Soares, Vera; Sniehotta, Falko F; Sund, Reijo; Vasankari, Tommi; Absetz, Pilvikki; Borodulin, Katja; Uutela, Antti; Lintunen, Taru; Haukkala, Ari

2016-05-27

Physical activity (PA) has been shown to decline during adolescence, and those with lower education have lower levels of activity already at this age, calling for targeted efforts for them. No previous study has demonstrated lasting effects of school-based PA interventions among older adolescents. Furthermore, these interventions have rarely targeted sedentary behaviour (SB) despite its relevance to health. The Let's Move It trial aims to evaluate the effectiveness and the cost-effectiveness of a school-based, multi-level intervention, on PA and SB, among vocational school students. We hypothesise that the intervention is effective in increasing moderate-to-vigorous-intensity physical activity (MVPA), particularly among those with low or moderate baseline levels, and decreasing SB among all students. The design is a cluster-randomised parallel group trial with an internal pilot study. The trial is conducted in six vocational schools in the Helsinki Metropolitan area, Finland. The intervention is carried out in 30 intervention classes, and 27 control classes retain the standard curriculum. The randomisation occurs at school-level to avoid contamination and to aid delivery. Three of the six schools, randomly allocated, receive the 'Let's Move It' intervention which consists of 1) group sessions and poster campaign targeting students' autonomous PA motivation and self-regulation skills, 2) sitting reduction in classrooms via alterations in choice architecture and teacher behaviour, and 3) enhancement of PA opportunities in school, home and community environments. At baseline, student participants are blind to group allocation. The trial is carried out in six batches in 2015-2017, with main measurements at pre-intervention baseline, and 2-month and 14-month follow-ups. Primary outcomes are for PA, MVPA measured by accelerometry and self-report, and for SB, sedentary time and breaks in sedentary time (accelerometry). Key secondary outcomes include measured body composition, self-reported well-being, and psychological variables. Process variables include measures of psychosocial determinants of PA (e.g. autonomous motivation) and use of behaviour change techniques. Process evaluation also includes qualitative interviews. Intervention fidelity is monitored. The study will establish whether the Let's Move It intervention is effective in increasing PA and reducing SB in vocational school students, and identify key processes explaining the results. ISRCTN10979479 . Registered: 31.12.2015.

K-Ras protein as a drug target.

PubMed

McCormick, Frank

2016-03-01

K-Ras proteins are major drivers of human cancers, playing a direct causal role in about one million cancer cases/year. In cancers driven by mutant K-Ras, the protein is locked in the active, GTP-bound state constitutively, through a defect in the off-switch mechanism. As such, the mutant protein resembles the normal K-Ras protein from a structural perspective, making therapeutic attack extremely challenging. K-Ras is a member of a large family of related proteins, which share very similar GDP/GTP-binding domains, making specific therapies more difficult. Furthermore, Ras proteins lack pockets to which small molecules can bind with high affinity, with a few interesting exceptions. However, new insights into the structure and function of K-Ras proteins reveal opportunities for intervention that were not appreciated many years ago, when efforts were launched to develop K-Ras therapies. Furthermore, K-Ras undergoes post-translational modification and interactions with cellular signaling proteins that present additional therapeutic opportunities, such as specific binding to calmodulin and regulation of non-canonical Wnt signaling.

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling

DOE PAGES

Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.; ...

2018-03-05

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.

PubMed

Erickson, Keesha E; Rukhlenko, Oleksii S; Posner, Richard G; Hlavacek, William S; Kholodenko, Boris N

2018-03-05

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisition of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers. Copyright © 2018 Elsevier Ltd. All rights reserved.

SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a

PubMed Central

Wisner, Stephanie A; Chen, Xiao; Spiegelman, Nicole A; Linder, Maurine E

2017-01-01

Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation. PMID:29239724

Physical activity and sedentary behaviour among Asian and Anglo-Australian adolescents.

PubMed

Strugnell, Claudia; M N Renzaho, Andre; Ridley, Kate; Burns, Cate

2015-08-01

Evidence suggests that physical activity (PA) and sedentary behaviour (SB) participation varies among culturally and linguistically diverse (CALD) adolescents. The present study examined differences in PA and SB among a CALD sample of Chinese Australian, South-east Asian and Anglo-Australian adolescents. Data from 286 adolescents aged 12-16 years involved in the Chinese and Australian Adolescent Health Survey in metropolitan Melbourne, Australia, were analysed. Accelerometry outcomes included median activity counts per minute (counts x min(-1)) and minutes per day (min x day(-1)) spent in light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA) and sedentary time (ST). Kruskal-Wallis one-way analysis of variance and sequential multiple hierarchical linear regressions were used to examine CALD differences in PA and ST. Multivariate analyses of accelerometry data found Chinese Australian and South-east Asian adolescents engaged in significantly less daily MVPA (5-8 min x day(-1)) and LPA (50-58 min x day(-1); P < 0.05), but greater daily ST (40-41 min x day(-1)), than Anglo-Australian adolescents, after adjusting for age, gender and socioeconomic category. The results demonstrate lower engagement in daily MVPA and LPA and greater engagement in ST using accelerometry among Chinese Australian and South-east Asian adolescents compared with Anglo-Australian adolescents. These findings have important public health implications in furthering our understanding of CALD differences in PA and SB. SO WHAT? An understanding of the CALD differences in physical activity and sedentary behaviour among Australian adolescents has important implications for intervention planning and delivery as well as the wider health implications of these behaviours. This article furthers the current understanding of CALD adolescents' participation in physical activity and sedentary behaviour, of which limited information is available.

Ras signaling in aging and metabolic regulation.

PubMed

Slack, Cathy

2017-12-07

Aberrant signal transduction downstream of the Ras GTPase has a well-established role in tumorigenesis. Mutations that result in hyperactivation of Ras are responsible for a third of all human cancers. Hence, small molecule inhibitors of the Ras signal transduction cascade have been under intense focus as potential cancer treatments. In both invertebrate and mammalian models, emerging evidence has also implicated components of the Ras signaling pathway in aging and metabolic regulation. Here, I review the current evidence for Ras signaling in these newly discovered roles highlighting the interactions between the Ras pathway and other longevity assurance mechanisms. Defining the role of Ras signaling in maintaining age-related health may have important implications for the development of interventions that could not only increase lifespan but also delay the onset and/or progression of age-related functional decline.

Ras inhibitors display an anti-metastatic effect by downregulation of lysyl oxidase through inhibition of the Ras-PI3K-Akt-HIF-1α pathway.

PubMed

Yoshikawa, Yoko; Takano, Osamu; Kato, Ichiro; Takahashi, Yoshihisa; Shima, Fumi; Kataoka, Tohru

2017-12-01

Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-ras G12V gene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or a siRNA targeting Ras downregulates the expression of lysyl oxidase (LOX), which has been implicated in metastasis. LOX expression is enhanced by co-expression of Ras G12V through activation of phosphatidylinositol 3-kinase (PI3K)/Akt and concomitant accumulation of hypoxia-inducible factor (HIF)-1α. Furthermore, Kobe0065 effectively inhibits not only migration and invasion of cancer cells carrying the activated ras genes but also lung metastasis of human CRC cell line SW620 carrying the K-ras G12V gene. Collectively, these results indicate that Kobe0065 prevents metastasis through inhibition of the Ras-PI3K-Akt-HIF-1α-LOX signaling and suggest that Ras inhibitors in general might exhibit both anti-proliferative and anti-metastatic properties toward cancer cells carrying the activated ras genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring environmental causes of altered ras effects: fragmentation plus integration?

PubMed

Porta, Miquel; Ayude, Daniel; Alguacil, Juan; Jariod, Manuel

2003-02-01

Mutations in ras genes are the most common abnormality of oncogenes in human cancer and a major example of activation by point mutation. Experimental and epidemiological studies support the notion that Ki-ras activation and expression may be chemically related. We discuss the potential role of several environmental compounds in the induction or promotion of ras mutations in humans, with a focus on exocrine pancreatic cancer, the human tumor with the highest prevalence at diagnosis of Ki-ras mutations. Organochlorine compounds, organic solvents, and coffee compounds may play an indirect role in causing Ki-ras mutations, rather than as direct inducers of the mutations. Although for some organochlorine compounds the induction of point mutations in ras oncogenes cannot be excluded, it seems more likely that the effects of these compounds are mediated through nongenomic or indirectly genotoxic mechanisms of action. Organic solvents also may act via enzymatic induction of ras mutagens or by providing a proliferation advantage to ras-mutated cell clones. In exocrine pancreatic cancer, caffeine, other coffee compounds, or other factors with which coffee drinking is associated could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. Asbestos, cigarette smoking, and some dietary factors also may be involved in the initiation or the promotion of Ki-ras mutations in lung and colon cancers. Further development of the mechanistic scenarios proposed here could contribute to a meaningful integration of biological, clinical, and environmental knowledge on the causes of altered ras effects. Copyright 2003 Wiley-Liss, Inc.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

PubMed Central

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies

PubMed Central

Bueno, Anibal; Morilla, Ian; Diez, Diego; Moya-Garcia, Aurelio A.; Lozano, José; Ranea, Juan A.G.

2016-01-01

RAS proteins are the founding members of the RAS superfamily of GTPases. They are involved in key signaling pathways regulating essential cellular functions such as cell growth and differentiation. As a result, their deregulation by inactivating mutations often results in aberrant cell proliferation and cancer. With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. Our results show that many RAS proteins with divergent sequences are found close together in the human interactome. We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. These results underscore the potential relevance of cross-talking in the RAS signaling network, which should be taken into account when considering the inhibitory activity of drugs targeting specific RAS oncoproteins. This study broadens our understanding of the human RAS signaling network and stresses the importance of considering its potential cross-talk in future therapies. PMID:27713118

Coating Thermoelectric Devices To Suppress Sublimation

NASA Technical Reports Server (NTRS)

Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

2007-01-01

A technique for suppressing sublimation of key elements from skutterudite compounds in advanced thermoelectric devices has been demonstrated. The essence of the technique is to cover what would otherwise be the exposed skutterudite surface of such a device with a thin, continuous film of a chemically and physically compatible metal. Although similar to other sublimation-suppression techniques, this technique has been specifically tailored for application to skutterudite antimonides. The primary cause of deterioration of most thermoelectric materials is thermal decomposition or sublimation - one or more elements sublime from the hot side of a thermoelectric couple, changing the stoichiometry of the device. Examples of elements that sublime from their respective thermoelectric materials are Ge from SiGe, Te from Pb/Te, and now Sb from skutterudite antimonides. The skutterudite antimonides of primary interest are CoSb3 [electron-donor (n) type] and CeFe(3-x)Co(x)Sb12 [electron-acceptor (p) type]. When these compounds are subjected to typical operating conditions [temperature of 700 C and pressure <10(exp -5) torr (0.0013 Pa)], Sb sublimes from their surfaces, with the result that Sb depletion layers form and advance toward their interiors. As the depletion layer advances in a given device, the change in stoichiometry diminishes the thermal-to-electric conversion efficiency of the device. The problem, then, is to prevent sublimation, or at least reduce it to an acceptably low level. In preparation for an experiment on suppression of sublimation, a specimen of CoSb3 was tightly wrapped in a foil of niobium, which was selected for its chemical stability. In the experiment, the wrapped specimen was heated to a temperature of 700 C in a vacuum of residual pressure <10(exp -5) torr (0.0013 Pa), then cooled and sectioned. Examination of the sectioned specimen revealed that no depletion layer had formed, indicating the niobium foil prevented sublimation of antimony at 700 C. This was a considerable improvement, considering that uncoated CoSb3 had been found to decompose to form the lowest antimonide at the surface at only 600 C. Evidently, because the mean free path of Sb at the given temperature and pressure was of the order of tens of centimeters, any barrier closer than tens of centimeters (as was the niobium foil) would have suppressed transport of Sb vapor, thereby suppressing sublimation of Sb

The Ras/Raf signaling pathway is required for progression of mouse embryos through the two-cell stage.

PubMed Central

Yamauchi, N; Kiessling, A A; Cooper, G M

1994-01-01

We have used microinjection of antisense oligonucleotides, monoclonal antibody, and the dominant negative Ras N-17 mutant to interfere with Ras expression and function in mouse oocytes and early embryos. Microinjection of either ras antisense oligonucleotides or anti-Ras monoclonal antibody Y13-259 did not affect normal progression of oocytes through meiosis and arrest at metaphase II. However, microinjection of fertilized eggs with constructs expressing Ras N-17 inhibited subsequent development through the two-cell stage. The inhibitory effect of Ras N-17 was overcome by simultaneous injection of a plasmid expressing an active raf oncogene, indicating that it resulted from interference with the Ras/Raf signaling pathway. In contrast to the inhibition of two-cell embryo development resulting from microinjection of pronuclear stage eggs, microinjection of late two-cell embryos with Ras N-17 expression constructs did not affect subsequent cleavages and development to morulae and blastocysts. It thus appears that the Ras/Raf signaling pathway, presumably activated by autocrine growth factor stimulation, is specifically required at the two-cell stage, which is the time of transition between maternal and embryonic gene expression in mouse embryos. Images PMID:7935384

Vibrational Stark effect spectroscopy reveals complementary electrostatic fields created by protein-protein binding at the interface of Ras and Ral.

PubMed

Walker, David M; Hayes, Ellen C; Webb, Lauren J

2013-08-07

Electrostatic fields at the interface of the GTPase H-Ras (Ras) docked with the Ras binding domain of the protein Ral guanine nucleoside dissociation stimulator (Ral) were measured with vibrational Stark effect (VSE) spectroscopy. Nine residues on the surface of Ras that participate in the protein-protein interface were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe into the protein-protein interface. The absorption energy of the nitrile was measured both on the surface of Ras in its monomeric state, then after incubation with the Ras binding domain of Ral to form the docked complex. Boltzmann-weighted structural snapshots of the nitrile-labeled Ras protein were generated both in monomeric and docked configurations from molecular dynamics simulations using enhanced sampling of the cyanocysteine side chain's χ2 dihedral angle. These snapshots were used to determine that on average, most of the nitrile probes were aligned along the Ras surface, parallel to the Ras-Ral interface. The average solvent-accessible surface areas (SASA) of the cyanocysteine side chain were found to be <60 Å(2) for all measured residues, and was not significantly different whether the nitrile was on the surface of the Ras monomer or immersed in the docked complex. Changes in the absorption energy of the nitrile probe at nine positions along the Ras-Ral interface were compared to results of a previous study examining this interface with Ral-based probes, and found a pattern of low electrostatic field in the core of the interface surrounded by a ring of high electrostatic field around the perimeter of the interface. These data are used to rationalize several puzzling features of the Ras-Ral interface.

Cost-effectiveness of RAS screening before monoclonal antibodies therapy in metastatic colorectal cancer based on FIRE3 Study

PubMed Central

Wen, Feng; Yang, Yu; Zhang, Pengfei; Zhang, Jian; Zhou, Jing; Tang, Ruilei; Chen, Hongdou; Zheng, Hanrui; Fu, Ping; Li, Qiu

2015-01-01

The surprising results published by FIRE-3 revealed that the overall survival (OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The substantial increase in testing and treatment costs, however, impose a considerable health burden on patients and society. Hence the study was aimed to assess the cost-effectiveness of RAS screening before monoclonal antibodies (mAbs) therapy based on FIRE-3 study. Four groups were analyzed: group 1, patients with KRAS testing treated with Cmab and FOLFIRI; group 2, patients with RAS testing treated with Cmab and FOLFIRI; group 3, patients with KRAS testing treated with bevacizumab(Bmab) and FOLFIRI; group 4, patients with RAS testing treated with Bmab and FOLFIRI. A Markov model comprising 3 health states (progression-free survival, progressive disease and death) was built. The costs were calculated from a Chinese payer perspective, and survival was reported in quality-adjusted life-months (QALMs). Average total lifetime costs ranged from $104,682.44 (RAS-Bmab) to $136,867.44 (RAS-Cmab), while the survival gained varied from 16.88 QALMs in RAS-Bmab to 21.85 QALMs in RAS-Cmab. The cost per QALM was $6,263.86 for RAS-Cmab, $6,145.84 for KRAS-Bmab, $6,201.57 for RAS-Bmab and $6,960.70 for KRAS-Cmab respectively. The KRAS-Cmab strategy was dominated by the other 3 groups. The first-treatment cost of RAS-Cmab was the most influential one to the model. In all, the RAS screening prior to Cmab treatment in mCRC seems to be a cost-effective strategy in the time of monoclonal antibodies (mAbs) therapy with the most gained QALMs. PMID:26418570

The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis.

PubMed

Tsujita, Maristela; Batista, Wagner L; Ogata, Fernando T; Stern, Arnold; Monteiro, Hugo P; Arai, Roberto J

2008-05-16

p21Ras protein plays a critical role in cellular signaling that induces either cell cycle progression or apoptosis. Nitric oxide (NO) has been consistently reported to activate p21Ras through the redox sensitive cysteine residue (118). In this study, we demonstrated that the p21Ras-ERK pathway regulates THP-1 monocyte/macrophage apoptosis induced by S-nitrosoglutathione (SNOG). This was apparent from studies in THP-1 cells expressing NO-insensitive p21Ras (p21Ras(C118S)) where the pro-apoptotic action of SNOG was almost abrogated. Three major MAP kinase pathways (ERK, JNK, and p38) that are downstream to p21Ras were investigated. It was observed that only the activation of ERK1/2 MAP kinases by SNOG in THP-1 cells was attributable to p21Ras. The inhibition of the ERK pathway by PD98059 markedly attenuated apoptosis in SNOG-treated THP-1 cells, but had a marginal effect on SNOG-treated THP-1 cells expressing NO-insensitive p21Ras. The inhibition of the JNK and p38 pathways by selective inhibitors had no marked effects on the percentage of apoptosis. The induction of p21Waf1 expression by SNOG was observed in THP-1 cells harboring mutant and wild-type p21Ras, however in cells expressing mutant Ras, the expression of p21Waf1 was significantly attenuated. The treatment of THP-1 cells expressing wild-type p21Ras with PD98059 resulted in significant attenuation of p21Waf1 expression. These results indicate that the redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by SNOG.

The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsujita, Maristela; Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, SP; Batista, Wagner L.

2008-05-16

p21Ras protein plays a critical role in cellular signaling that induces either cell cycle progression or apoptosis. Nitric oxide (NO) has been consistently reported to activate p21Ras through the redox sensitive cysteine residue (118). In this study, we demonstrated that the p21Ras-ERK pathway regulates THP-1 monocyte/macrophage apoptosis induced by S-nitrosoglutathione (SNOG). This was apparent from studies in THP-1 cells expressing NO-insensitive p21Ras (p21Ras{sup C118S}) where the pro-apoptotic action of SNOG was almost abrogated. Three major MAP kinase pathways (ERK, JNK, and p38) that are downstream to p21Ras were investigated. It was observed that only the activation of ERK1/2 MAP kinasesmore » by SNOG in THP-1 cells was attributable to p21Ras. The inhibition of the ERK pathway by PD98059 markedly attenuated apoptosis in SNOG-treated THP-1 cells, but had a marginal effect on SNOG-treated THP-1 cells expressing NO-insensitive p21Ras. The inhibition of the JNK and p38 pathways by selective inhibitors had no marked effects on the percentage of apoptosis. The induction of p21Waf1 expression by SNOG was observed in THP-1 cells harboring mutant and wild-type p21Ras, however in cells expressing mutant Ras, the expression of p21Waf1 was significantly attenuated. The treatment of THP-1 cells expressing wild-type p21Ras with PD98059 resulted in significant attenuation of p21Waf1 expression. These results indicate that the redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by SNOG.« less

Influence of the selenium content on thermo-mechanical and optical properties of Ge-Ga-Sb-S chalcogenide glasses

NASA Astrophysics Data System (ADS)

Ye, Bin; Dai, Shixun; Wang, Rongping; Tao, Guangming; Zhang, Peiqing; Wang, Xunsi; Shen, Xiang

2016-07-01

A number of Ge17Ga4Sb10S69-xSex (x = 0, 15, 30, 45, 60, and 69) chalcogenide glasses have been synthesized by a melt-quenching method to investigate the effect of the Se content on thermo-mechanical and optical properties of these glasses. While it was found that the glass transition temperature (Tg) decreases from 261 to 174 °C with increasing Se contents, crystallization temperature (Tc) peak only be observed in glasses with Se content of x = 45. It was evident from the measurements of structural and physical properties that changes of the glass network bring an apparent impact on the glass properties. Also, the substitution of Se for S in Ge-Ga-Sb glasses can significantly improve the thermal stability against crystallization and broaden the infrared transmission region.

Origin of the low critical observing temperature of the quantum anomalous Hall effect in V-doped (Bi, Sb) 2Te 3 film

DOE PAGES

Li, W.; Claassen, M.; Chang, Cui -Zu; ...

2016-09-07

The experimental realization of the quantum anomalous Hall (QAH) effect in magnetically-doped (Bi, Sb) 2Te 3 films stands out as a landmark of modern condensed matter physics. However, ultra-low temperatures down to few tens of mK are needed to reach the quantization of Hall resistance, which is two orders of magnitude lower than the ferromagnetic phase transition temperature of the films. Here, we systematically study the band structure of V-doped (Bi, Sb) 2Te 3 thin films by angle-resolved photoemission spectroscopy (ARPES) and show unambiguously that the bulk valence band (BVB) maximum lies higher in energy than the surface state Diracmore » point. Finally, our results demonstrate clear evidence that localization of BVB carriers plays an active role and can account for the temperature discrepancy.« less

Thermal activation in Co/Sb nanoparticle-multilayer thin films

NASA Astrophysics Data System (ADS)

Madden, Michael R.

Multilayer "Co" /"Sb" thin films created via electron-beam physical vapor deposition are known to exhibit thermally activated dynamics. Scanning tunneling microscopy has indicated that the "Co" forms nanoparticles within an "Sb" matrix during deposition and subsequently forms nanowires by way of NP migration within the interstices of the confining layers. The electrical resistance of these systems decays during this irreversible aging process in a manner well-modeled by an Arrhenius law. Presently, this phenomenon is shown to possess some degree of tunability with respect to "Co" layer thickness tCo as well as deposition temperature Tdep , whereby characteristic timescales increase with either parameter. Furthermore, fluctuation timescales and activation energies seem to decrease and increase respectively with increasing t Co. An easily calibrated, one-time-use, time-temperature switch based on such systems lies within the realm of plausibility. The results presented here can be considered to be part of an ongoing development of the concept.

Fabrication of 121Sb isotopic targets for the study of nuclear high spin features

NASA Astrophysics Data System (ADS)

Devi, K. Rojeeta; Kumar, Suresh; Kumar, Neeraj; Abhilash, S. R.; Kabiraj, D.

2018-06-01

Isotopic 121Sb targets with 197Au backing have been prepared by Physical Vapor Deposition (PVD) method using the diffusion pump based coating unit at target laboratory, Inter University Accelerator Centre (IUAC), New Delhi, India. The target thickness was measured by stylus profilo-meter and the purity of the targets was investigated by Energy Dispersive X-ray Analysis (EDXA). One of these targets has been used in an experiment which was performed at IUAC for nuclear structure study through fusion evaporation reaction. The excitation function of the 121Sb(12C, yxnγ) reaction has been performed for energies 58 to 70 MeV in steps of 4 MeV. The experimental results were compared with the calculations of statistical models : PACE4 and CASCADE. The methods adopted to achieve best quality foils and good deposition efficiency are reported in this paper.

Mobile Plant Laboratory.

ERIC Educational Resources Information Center

Carrier, Judy

1979-01-01

Describing the North Carolina Botanical Garden's horticultural therapy program, which provides activity therapy for the mental and physical well-being of people of all ages, this article details an educational training program. Journal availabillity: see RC 503 504. (SB)

A physically-based channel-modeling framework integrating HEC-RAS sediment transport capabilities and the USDA-ARS bank-stability and toe-erosion model (BSTEM)

USDA-ARS?s Scientific Manuscript database

Classical, one-dimensional, mobile bed, sediment-transport models simulate vertical channel adjustment, raising or lowering cross-section node elevations to simulate erosion or deposition. This approach does not account for bank erosion processes including toe scour and mass failure. In many systems...

The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

NASA Astrophysics Data System (ADS)

Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

2016-02-01

Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP-GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer.

H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.

PubMed

Martín-Sánchez, Paloma; Luengo, Alicia; Griera, Mercedes; Orea, María Jesús; López-Olañeta, Marina; Chiloeches, Antonio; Lara-Pezzi, Enrique; de Frutos, Sergio; Rodríguez-Puyol, Manuel; Calleros, Laura; Rodríguez-Puyol, Diego

2018-02-01

Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H- ras gene deletion produces mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent mechanism. In this study, we analyzed the consequences of H- ras deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras knockout (H -ras -/- ) and control wild-type (H -ras +/+ ) mice, as were extracellular matrix protein expression. Increased cardiac PKG-Iβ protein expression in H -ras -/- mice suggests the involvement of this protein in heart protection. Ex vivo experiments on cardiac explants could support this mechanism, as PKG blockade blunted protection against AngII-induced cardiac hypertrophy and fibrosis markers in H -ras -/- mice. Genetic modulation studies in cardiomyocytes and cardiac and embryonic fibroblasts revealed that the lack of H-Ras down-regulates the B-RAF/MEK/ERK pathway, which induces the glycogen synthase kinase-3β-dependent activation of the transcription factor, cAMP response element-binding protein, which is responsible for PKG-Iβ overexpression in H -ras -/- mouse embryonic fibroblasts. This study demonstrates that H- ras deletion protects against AngII-induced cardiac remodeling, possibly via a mechanism in which PKG-Iβ overexpression could play a partial role, and points to H-Ras and/or downstream proteins as potential therapeutic targets in cardiovascular disease.-Martín-Sánchez, P., Luengo, A., Griera, M., Orea, M. J., López-Olañeta, M., Chiloeches, A., Lara-Pezzi, E., de Frutos, S., Rodríguez-Puyol, M., Calleros, L., Rodríguez-Puyol, D. H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.

The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Han-Soo; Kim, Ju Won; Gang, Jingu

2006-09-15

LB42708 (LB7) and LB42908 (LB9) are pyrrole-based orally active farnesyltransferase inhibitors (FTIs) that have similar structures. The in vitro potencies of these compounds against FTase and GGTase I are remarkably similar, and yet they display different activity in apoptosis induction and morphological reversion of ras-transformed rat intestinal epithelial (RIE) cells. Both FTIs induced cell death despite K-ras prenylation, implying the participation of Ras-independent mechanism(s). Growth inhibition by these two FTIs was accompanied by G1 and G2/M cell cycle arrests in H-ras and K-ras-transformed RIE cells, respectively. We identified three key markers, p21{sup CIP1/WAF1}, RhoB and EGFR, that can explain themore » differences in the molecular mechanism of action between two FTIs. Only LB7 induced the upregulation of p21{sup CIP1/WAF1} and RhoB above the basal level that led to the cell cycle arrest and to distinct morphological alterations of ras-transformed RIE cells. Both FTIs successfully inhibited the ERK and activated JNK in RIE/K-ras cells. While the addition of conditioned medium from RIE/K-ras reversed the growth inhibition of ras-transformed RIE cells by LB9, it failed to overcome the growth inhibitory effect of LB7 in both H-ras- and K-ras-transformed RIE cells. We found that LB7, but not LB9, decreased the expression of EGFRs that confers the cellular unresponsiveness to EGFR ligands. These results suggest that LB7 causes the induction of p21{sup CIP1/WAF1} and RhoB and downregulation of EGFR that may serve as critical steps in the mechanism by which FTIs trigger irreversible inhibitions on the cell growth and apoptosis in ras-transformed cells.« less

Radiology Physician Extenders: A Literature Review of the History and Current Roles of Physician Extenders in Medical Imaging.

PubMed

Sanders, Vicki L; Flanagan, Jennifer

2015-01-01

The purpose of the literature review was to assess the origins of radiology physician extenders and examine the current roles found in the literature of advanced practice physician extenders within medical imaging. Twenty-six articles relating to physician assistants (PAs), nurse practitioners (NPs), radiologist assistants (RAs), and nuclear medicine advanced associates (NMAAs) were reviewed to discern similarities and differences in history, scope of practice, and roles in the medical imaging field. The literature showed PAs and NPs are working mostly in interventional radiology. PAs, NPs, and RAs perform similar tasks in radiology, including history and physicals, evaluation and management, preprocedure work-up, obtaining informed consent, initial observations/reports, and post-procedure follow-up. NPs and PAs perform a variety of procedures but most commonly vascular access, paracentesis, and thoracentesis. RAs perform gastrointestinal, genitourinary, nonvascular invasive fluoroscopy procedures, and vascular access procedures. The review revealed NMAAs are working in an advanced role, but no specific performances of procedures was found in the literature, only suggested tasks and clinical competencies. PAs, NPs, and RAs are currently the three main midlevel providers used in medical imaging. These midlevel providers are being used in a variety of ways to increase the efficiency of the radiologist and provide diagnostic and therapeutic radiologic procedures to patients. NMAAs are being used in medical imaging but little literature is available on current roles in clinical practice. More research is needed to assess the exact procedures and duties being performed by these medical imaging physician extenders.

High-fat diet-mediated dysbiosis promotes intestinal carcinogenesis independent of obesity

PubMed Central

Schulz, Manon D.; Atay, Çigdem; Heringer, Jessica; Romrig, Franziska K.; Schwitalla, Sarah; Aydin, Begüm; Ziegler, Paul K.; Varga, Julia; Reindl, Wolfgang; Pommerenke, Claudia; Salinas-Riester, Gabriela; Böck, Andreas; Alpert, Carl; Blaut, Michael; Polson, Sara C.; Brandl, Lydia; Kirchner, Thomas; Greten, Florian R.; Polson, Shawn W.; Arkan, Melek C.

2014-01-01

Summary Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers1. There is substantial evidence suggesting that diet profoundly affects the composition of the intestinal microbiota2. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development3. Yet the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that HFD promotes tumor progression in the small intestine of genetically susceptible K-rasG12Dint mice independently of obesity. HFD consumption in conjunction with K-Ras mutation mediates a shift in the composition of gut microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHC-II presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized, and tumor progression attenuated, when K-rasG12Dint mice are supplemented with butyrate. Importantly, Myd88-deficiency blocks tumor progression. Transfer of fecal samples from diseased donors into healthy adult K-rasG12Dint mice is sufficient to transmit disease in the absence of HFD. Furthermore, treatment with antibiotics completely blocks HFD-induced tumor progression suggesting a pivotal role for distinct microbial shifts in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting microbiota that favor carcinogenesis, and suggest tumorigenesis may be transmissible among genetically predisposed individuals. PMID:25174708

R-Ras contributes to LTP and contextual discrimination.

PubMed

Darcy, M J; Jin, S-X; Feig, L A

2014-09-26

The ability to discriminate between closely related contexts is a specific form of hippocampal-dependent learning that may be impaired in certain neurodegenerative disorders such as Alzheimer's and Down Syndrome. However, signaling pathways regulating this form of learning are poorly understood. Previous studies have shown that the calcium-dependent exchange factor Ras-GRF1, an activator of Rac, Ras and R-Ras GTPases, is important for this form of learning and memory. Moreover, the ability to discriminate contexts was linked to the ability of Ras-GRF1 to promote high-frequency stimulation long-term potentiation (HFS-LTP) via the activation of p38 Map kinase. Here, we show that R-Ras is involved in this form of learning by using virally-delivered miRNAs targeting R-Ras into the CA1 region of the dorsal hippocampus and observing impaired contextual discrimination. Like the loss of GRF1, knockdown of R-Ras in the CA1 also impairs the induction of HFS-LTP and p38 Map kinase. Nevertheless, experiments indicate that this involvement of R-Ras in HFS-LTP that is required for contextual discrimination is independent of Ras-GRF1. Thus, R-Ras is a novel regulator of a form of hippocampal-dependent LTP as well as learning and memory that is affected in certain forms of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence

PubMed Central

Benanti, Jennifer A.; Galloway, Denise A.

2004-01-01

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated β-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS. PMID:15024073

Identification of Ras-degrading small molecules that inhibit the transformation of colorectal cancer cells independent of β-catenin signaling.

PubMed

Shin, Wookjin; Lee, Sang-Kyu; Hwang, Jeong-Ha; Park, Jong-Chan; Cho, Yong-Hee; Ro, Eun Ji; Song, Yeonhwa; Seo, Haeng Ran; Choi, Kang-Yell

2018-06-06

Although the development of drugs that control Ras is an emerging topic in cancer therapy, no clinically applicable drug is currently available. We have previously utilized knowledge of the Wnt/β-catenin signaling-dependent mechanism of Ras protein stability regulation to identify small molecules that inhibit the proliferation and transformation of various colorectal cancer (CRC) cells via degradation of both β-catenin and Ras. Due to the absence of Ras degradation in cells expressing a nondegradable mutant form of β-catenin and the need to determine an alternative mechanism of Ras degradation, we designed a cell-based system to screen compounds that degrade Ras independent of the Wnt/β-catenin signaling pathway. A cell-based high-content screening (HCS) system that monitors the levels of EGFP-K-Ras G12V was established using HCT-116 cells harboring a nondegradable mutant CTNNB1 (ΔS45). Through HCS of a chemical library composed of 10,000 compounds and subsequent characterization of hits, we identified several compounds that degrade Ras without affecting the β-catenin levels. KY7749, one of the most effective compounds, inhibited the proliferation and transformation of CRC cells, especially KRAS-mutant cells that are resistant to the EGFR monoclonal antibody cetuximab. Small molecules that degrade Ras independent of β-catenin may able to be used in treatments for cancers caused by aberrant EGFR and Ras.

High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

PubMed

Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2018-05-01

K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

DA-Raf, a dominant-negative antagonist of the Ras-ERK pathway, is a putative tumor suppressor.

PubMed

Kanno, Emiri; Kawasaki, Osamu; Takahashi, Kazuya; Takano, Kazunori; Endo, Takeshi

2018-01-01

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Imaging of Ras/Raf activity induced by low energy laser irradiation in living cell using FRET

NASA Astrophysics Data System (ADS)

Wang, Fang; Chen, Tong-Sheng; Xing, Da

2005-01-01

Ras/Raf signaling pathway is an important signaling pathway that governs cell proliferation, differential and apoptosis. Low-energy laser irradiation (LELI) was found to modulate various processes. Generally, cell proliferation is induced by low doses LELI and apoptosis is induced by high doses LELI. Mechanism of biological effect of LELI has not been clear. Recently, activation of MEK (mitogen-activated protein kinase) and ERK (extracellular-signal-regulated kinase), which are downstream protein kinases of Ras/Raf, are observed during LELI-induced cell proliferation by immunoprecipitation and western blot analysis. RaichuRas reporter consisting of fusions of H-ras, the Ras-binding domain of Raf (RafRBD), a cyan fluorescent protein (CFP) and a yellow fluorescent protein (YFP). Therefore, intramolecular binding of GTP-Ras to RafRBD brings CFP close to YFP and increases FRET between CFP and YFP. Human lung adenocarcinoma cell line (ASTC-a-1) was transfected with the plasmid (pRaichuRas) and then treated with LELI at dose of 60J/cm2. Effect of LELI on Ras/Raf in physiological condition of living cells was observed by fluorescence resonance energy transfer (FRET) technique during lung adenocarcinoma cell apoptosis induced by high dose (60J/cm2) LELI. Experimental results showed that after high dose LELI treatment, the binding of Ras and Raf decreases obviously, Ras/Raf signaling pathway deregulates and cell apoptosis occurs.

Observation of a two-dimensional Fermi surface and Dirac dispersion in YbMnSb2

NASA Astrophysics Data System (ADS)

Kealhofer, Robert; Jang, Sooyoung; Griffin, Sinéad M.; John, Caolan; Benavides, Katherine A.; Doyle, Spencer; Helm, T.; Moll, Philip J. W.; Neaton, Jeffrey B.; Chan, Julia Y.; Denlinger, J. D.; Analytis, James G.

2018-01-01

We present the crystal structure, electronic structure, and transport properties of the material YbMnSb2, a candidate system for the investigation of Dirac physics in the presence of magnetic order. Our measurements reveal that this system is a low-carrier-density semimetal with a two-dimensional Fermi surface arising from a Dirac dispersion, consistent with the predictions of density-functional-theory calculations of the antiferromagnetic system. The low temperature resistivity is very large, suggesting that scattering in this system is highly efficient at dissipating momentum despite its Dirac-like nature.

Ballistic magnetotransport and spin-orbit interaction in indium antimonide and indium arsenide quantum wells

NASA Astrophysics Data System (ADS)

Peters, John Archibald

While charge transport in a two-dimensional electron system (2DES) is fairly well understood, many open experimental and theoretical questions related to the spin of electrons remain. The standard 2DES embedded in Alx Ga1-xAs/GaAs heterostructures is most likely not the optimal candidate for such investigations, since spin effects as well as spin-orbit interactions are small perturbations compared to other effects. This has brought InSb- and InAs-based material systems into focus due to the possibility of large spin-orbit interactions. By utilizing elastic scattering off a lithographic barrier, we investigate the consequence of spin on different electron trajectories observed in InSb and InAs quantum wells. We focus on the physical properties of spin-dependent reflection in a 2DES and we present experimental results demonstrating a method to create spin-polarized beams of ballistic electrons in the presence of a lateral potential barrier. Spatial separation of electron spins using cyclotron motion in a weak magnetic is also achieved via transverse magnetic focusing. We also explore electrostatic gating effects in InSb/InAlSb heterostructures and demonstrate the effective use of polymethylglutarimide (PMGI) as a gate dielectric for InSb. The dependence on temperature and on front gate voltage of mobility and density are also examined, revealing a strong dependence of mobility on density. As regards front gate action, there is saturation in the density once it reaches a limiting value. Further, we investigate antidot lattices patterned on InSb/InAlSb and InAs/AlGaSb heterostructures. At higher magnetic fields, ballistic commensurability features are displayed while at smaller magnetic fields localization and quantized oscillatory phenomena appear, with marked differences between InSb and InAs. Interesting localization behavior is exhibited in InSb, with the strength of the localization peak decreasing exponentially with temperature between 0.4 K and 50 K. InAs on the other hand show a strikingly modified antilocalization behavior, with small-period oscillations in magnetic field superposed. We also observe Altshuler-Aronov-Spivak oscillations in InSb and InAs antidot lattices and extract the phase and spin coherence lengths in InAs. Our experimental results are discussed in the light of localization and anti localization as probes of disorder and of spin dephasing mechanisms, modified by the artificial potential of the antidot lattice.

RAS - Target Identification - Informatics

Cancer.gov

The RAS Informatics lab group develops tools to track and analyze “big data” from the RAS Initiative, as well as analyzes data from external projects. By integrating internal and external data, this group helps improve understanding of RAS-driven cancers.

PI3K: A Crucial Piece in the RAS Signaling Puzzle.

PubMed

Krygowska, Agata Adelajda; Castellano, Esther

2018-06-01

RAS proteins are key signaling switches essential for control of proliferation, differentiation, and survival of eukaryotic cells. RAS proteins are mutated in 30% of human cancers. In addition, mutations in upstream or downstream signaling components also contribute to oncogenic activation of the pathway. RAS proteins exert their functions through activation of several signaling pathways and dissecting the contributions of these effectors in normal cells and in cancer is an ongoing challenge. In this review, we summarize our current knowledge about how RAS regulates type I phosphatidylinositol 3-kinase (PI3K), one of the main RAS effectors. RAS signaling through PI3K is necessary for normal lymphatic vasculature development and for RAS-induced transformation in vitro and in vivo, especially in lung cancer, where it is essential for tumor initiation and necessary for tumor maintenance. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Dictyostelium RasG Is Required for Normal Motility and Cytokinesis, But Not Growth

PubMed Central

Tuxworth, Richard I.; Cheetham, Janet L.; Machesky, Laura M.; Spiegelmann, George B.; Weeks, Gerald; Insall, Robert H.

1997-01-01

RasG is the most abundant Ras protein in growing Dictyostelium cells and the closest relative of mammalian Ras proteins. We have generated null mutants in which expression of RasG is completely abolished. Unexpectedly, RasG − cells are able to grow at nearly wild-type rates. However, they exhibit defective cell movement and a wide range of defects in the control of the actin cytoskeleton, including a loss of cell polarity, absence of normal lamellipodia, formation of unusual small, punctate polymerized actin structures, and a large number of abnormally long filopodia. Despite their lack of polarity and abnormal cytoskeleton, mutant cells perform normal chemotaxis. However, rasG − cells are unable to perform normal cytokinesis, becoming multinucleate when grown in suspension culture. Taken together, these data suggest a principal role for RasG in coordination of cell movement and control of the cytoskeleton. PMID:9245789

Drugging the undruggable Ras: mission possible?

PubMed Central

Cox, Adrienne D.; Fesik, Stephen W.; Kimmelman, Alec C.; Luo, Ji; Der, Channing J.

2015-01-01

Despite more than three decades of intensive effort, no effective pharmacologic inhibitors of the Ras oncoproteins have reached the clinic, prompting the widely held perception that Ras proteins are “undruggable”. However, there is renewed hope that this is not the case. In this review, we summarize the progress and promise of five key directions. First, we focus on the prospects of direct inhibitors of Ras. Second, we revisit the issue of whether blocking Ras membrane association is a viable approach. Third, we assess the status of targeting Ras downstream effector signalling, arguably the most favourable current direction. Fourth, we address whether the search for synthetic lethal interactors of mutant RAS still holds promise. Finally, Ras-mediated changes in cell metabolism have recently been described. Can these changes be exploited for new therapeutic directions? We conclude with perspectives on how additional complexities, not yet fully understood, may impact each of these approaches. PMID:25323927

Genetic analysis of Ras genes in epidermal development and tumorigenesis

PubMed Central

Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

2013-01-01

Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

Individual, Social, and Environmental Correlates of Active Transportation Patterns in French Women.

PubMed

Perchoux, Camille; Enaux, Christophe; Oppert, Jean-Michel; Menai, Mehdi; Charreire, Hélène; Salze, Paul; Weber, Christiane; Hercberg, Serge; Feuillet, Thierry; Hess, Franck; Roda, Célina; Simon, Chantal; Nazare, Julie-Anne

2017-01-01

The objectives were (1) to define physical activity (PA) and sedentary behaviors (SB) patterns in daily life contexts (work, leisure, and transportation) in French working women from NutriNet-Santé web-cohort and (2) to identify pattern(s) of active transportation and their individual, social, and environmental correlates. 23,432 participants completed two questionnaires to evaluate PA and SB in daily life contexts and individual representations of residential neighborhood and transportation modes. Hierarchical cluster analysis was performed which identified 6 distinct movement behavior patterns: (i) active occupation, high sedentary leisure, (ii) sedentary occupation, low leisure, (iii) sedentary transportation, (iv) sedentary occupation and leisure, (v) active transportation, and (vi) active leisure. Multinomial logistic regressions were performed to identify correlates of the "active transportation" cluster. The perceived environmental characteristics positively associated with "active transportation" included "high availability of destinations around home," "presence of bicycle paths," and "low traffic." A "positive image of walking/cycling," the "individual feeling of being physically active," and a "high use of active transport modes by relatives/friends" were positively related to "active transportation," identified as a unique pattern regarding individual and environmental correlates. Identification of PA and SB context-specific patterns will help to understand movement behaviors' complexity and to design interventions to promote active transportation in specific subgroups.

The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling

PubMed Central

Sandri, Chiara; Caccavari, Francesca; Valdembri, Donatella; Camillo, Chiara; Veltel, Stefan; Santambrogio, Martina; Lanzetti, Letizia; Bussolino, Federico; Ivaska, Johanna; Serini, Guido

2012-01-01

During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1. PMID:22825554

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

PubMed

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

2016-01-22

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

EDITORIAL: Siberia Integrated Regional Study: multidisciplinary investigations of the dynamic relationship between the Siberian environment and global climate change

NASA Astrophysics Data System (ADS)

Gordov, E. P.; Vaganov, E. A.

2010-03-01

This is an editorial overview of the Siberia Integrated Regional Study (SIRS), which is a large-scale investigation of ongoing and future environmental change in Siberia and its relationship to global processes, approaches, existing challenges and future direction. Introduction The SIRS is a mega-project within the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which coordinates interdisciplinary, national and international activities in Northern Eurasia that follow the Earth System Science Program (ESSP) approach. Under the direction of the International Geosphere-Biosphere Program (IGBP), SIRS is one of the Integrated Regional Studies (IRS) that aims to investigate environmental change in Siberia under the current environment of global change, and the potential impact on Earth system dynamics [1]. The regions of interest are those that may function as 'choke or switch points' for the global Earth system, where changes in regional biophysical, biogeochemical and anthropogenic components may have significant consequences for the Earth system at the global scale. Siberia is a large and significant region that may compel change [2]. Regional consequences of global warming (e.g. anomalous increases in cold season temperatures) have already been documented for Siberia [3]. This result is also supported by climate modeling results for the 20th-22nd centuries [4]. Future climatic change threatens Siberia with the shift of permafrost boundaries northward, dramatic changes in land cover (redistribution among boreal forest, wetlands, tundra, and steppe zones often precipitated by fire regime change) and the entire hydrological regime of the territory [5-8]. These processes feed back to and influence climate dynamics through the exchange of energy, water, greenhouse gases and aerosols [9]. Even though there have been a handful of national and international projects focused on the Siberian environment, scientists have minimal knowledge about the processes that control change in this understudied region, particularly those concerning the primary components that influence regional climate (i.e. cloud cover, precipitation) and responses and feedbacks to and from terrestrial and aquatic systems. This provides a strong impetus for the SIRS project. SIRS was initiated at a boreal forest conference in Krasnoyarsk in 2002 under the auspices of the IGBP and ESSP regional strategy by Will Steffen (IGBP) and the Siberian Branch of the Russian Academy of Sciences (SB RAS). Russian and foreign scientific activities continued under the Siberian Center for Environmental Research and Training (SCERT) in 2003. In 2005, the Siberian Branch of the Russian National Committee (SB RNC) for IGBP endorsed these activities and recommended investigations focus on four major themes: quantification of the terrestrial biota full greenhouse gas budget, with a focus on the exchange between biota and atmosphere; monitoring and modeling of regional climate change impacts; development of SIRS informational-computational infrastructure; and development of a regional strategy of adaptation to and mitigation of the negative consequences of global change. SIRS development [10, 11] supports Siberian Earth science investigations funded by the RAS Foundation for Basic Research, the European Commission (EC), the International Science and Technology Center (ISTC) and the National Aeronautics and Space Administration (NASA). SB RNC is responsible for SIRS advances, and SCERT hosts the Committee office and houses major SIRS informational-computational infrastructure development. NEESPI (www.neespi.org/) serves as an IGBP and World Climate Research Programme (WCRP) external project, and as a NEESPI mega-project, SIRS has organized distribution centers in Krasnoyarsk and Tomsk to support NEESPI activity, and has coordinated training and educational activity aimed at young scientists. SIRS approaches and outcomes Organizational activity The 'Siberian Geosphere-Biosphere Program: integrated regional study of contemporary natural and climatic changes' is one of several funded interdisciplinary projects, and it serves to unite regional studies from 14 RAS and SB RAS institutes and 5 universities. In the course of this and similar national1 and international projects, ENVIROMIS and ENVIROMIS-2 (Environmental Observations, Modelling and Information Systems) was formed, which is the SIRS professional community comprising regional, national and international specialists dealing with Siberian environmental dynamics studies. Results of those and parallel projects were analyzed in by coordinated activities: 'Enviro-RISKS-Man-induced Environmental Risks: monitoring, management and remediation of man-made changes in Siberia' [12]. Currently, a new set of SB RAS integrated2 and international projects within the Asia-Pacific Network for Global Change Study (APN) and ISTC are under way. While a number of projects have been initiated and clustered under the SIRS umbrella and their results and data are distributed through the SIRS web portal (http://sirs.scert.ru/), the organizational SIRS infrastructure is inadequate. SIRS has neither SB RAS stable funding nor a dedicated Project Office. Both obstacles are a major concern for the SIRS governing body. Information-computational infrastructure development The SIRS informational-computational infrastructure, which is currently under extensive development, is designed to stimulate national and international cooperative Earth science investigations, easily exchange data and knowledge, coordinate activities, and optimize the usage of resources, services and applications [13]. The infrastructure is organized as a set of thematic, bilingual (Russian and English), internet-accessible informational-computational systems, the first of which is the scientific web portal ATMOS (http://atmos.iao.ru/). ATMOS is an integrated set of distributed topical websites, combining standard multimedia information with research databases, models and analytical tools for on-line use and visualization, designed primarily for atmospheric physics and chemistry (http://risks.scert.ru/)3 [12, 14]. These powerful tools have already promoted understanding of the interactions between Siberian ecosystems, the atmosphere and human dynamics, under the impact of global climate change. For example, the climate site of the Enviro-RISKS portal (http://climate.risks.scert.ru/) processes unique data sets, from monitoring and modeling regional meteorology, atmospheric pollution transformation/transport and climate, all of which are significant for dynamic regional assessments. This is a user-friendly, interactive web system that can be used for regional climate change assessment and visualization based upon standard meteorological data. All major reanalysis and climatic characteristics are provided (surface air temperature, pressure, humidity, precipitation, soil moisture, and geopotential height), and the users can (but do not need to) access the data files directly but freely receive the results of their analyses through the Grid Analysis and Display System (GrADS; www.iges.org/grads/) or Interactive Data Language (IDL; www.ittvis.com/idl/). Specific spatial and temporal domains can be selected, as well as a wide range of statistical analyses, data manipulations, and visualization tools (including animation) that may be required for global, continental, and regional climate change assessments. The SIRS infrastructure has become an indispensable tool, providing researchers with an open platform (portal plus tools) that may be used, adapted, enriched or altered on the basis of the specific scientific applications in regions of Siberia, the Russian Federation, and the northern exatropics. SIRS capacity building/young scientists' education/training The SIRS educational capacity building programme includes ENVIROMIS biannual Multidisciplinary Conference, CITES (Computational and Information Technologies for Environmental Sciences) biannual Young Scientists' School (YSS) and international conferences [15]. These include lecture courses for young scientists, training sessions, invited lectures and thematic workshops (www.scert.ru/en/conferences/). The first event was organized in 2000, and thereafter each year 50-70 young scientists from Russia and the Commonwealth of Independent States participate in CITES and ENVIROMIS conferences. These events are organized to support multidisciplinary education, contain no parallel sessions, are composed of about 50% students, and all presentations are posted to assist future professional activity. In the first years, these activities were supported internationally (INTAS, the EC International Cooperation Program within FP5 and FP6); however, recent activities have been supported by the Russian Foundation for Basic Research, the RF Ministry of Education and Science and the SB RAS. Some results gained in the course of SIRS projects being carried out, and current challenges While some findings on regional climate dynamics were reported in the EGU 2009 NEESPI session and in manuscripts listed on the NEESPI website (www.neespi.org/science/NEESPI_publications.pdf), a majority of them have been published in Russian journals and are still unknown in the international climatic community. However, additional reports can be found in the Enviro-RISKS final scientific report [16], mainly in the third volume devoted to climate change, terrestrial ecosystems and hydrology (www.dmi.dk/dmi/sr08-05-3.pdf). We have already established that temperatures have increased, particularly in the winter in Eastern Siberia (0.5°/decade), and the number of frost days (~1 day yr-1) and growing season length has also increased (~1 day yr-1) [17, 18]. Even more troubling is the potential for these transient phenomena to manifest themselves as nonlinear reactions to ongoing climatic change [19]. There are three main scientific research challenges to the SIRS community, which are also very important from a regional socio-economic point of view and for the global carbon cycle. Permafrost fate, especially its border shift, seriously threatens infrastructure and might form a significant carbon and methane source to the atmosphere. Climate-related drying would alter biogenic emissions in peatlands that have been deposited over millennia and would increase the potential for peat fires which cannot be extinguished. Temperature/precipitation/hydrology regime change, which might increase risks of forest and peat fires, thus changing significantly the carbon, terrestrial and hydrologic cycle of the region. Desert-steppe-forest-tundra ecosystem borders northward shifts, which will also change regional input into the global carbon and radiation balance and give rise to serious socio-economical consequences for local populations (i.e. alter potential agricultural lands). New in situ instrumentation, data sets, models and research are required to address these challenges. The SB RAS has adopted a long-term integrated project 'Development of the basic network for monitoring of natural and climatic processes in Siberia' to establish a network of dedicated sites and stations equipped with modern instrumentation to monitor environmental changes in the region. One example is the Zotino tall tower observatory (ZOTTO) launched a few years ago (www.sfu-kras.ru/science/achievement/zotto/public) [20]. It is anticipated that together with ZOTTO, the future SB RAS network will serve as an important source of reliable environmental data for analyses. Another important SIRS objective is the development of a high-resolution regional climate model that properly takes into account specifics of this region (e.g., presence of permafrost, interaction of the biosphere and terrestrial hydrology, etc). Development of an integrated model was recently discussed at the NEESPI Workshop (www.scert.ru/en/conferences/cites2009/) by leading SIRS specialists and their German and US partners. Conclusions Devoted to regional-global linkages, understanding, monitoring and assessment of global change impacts on a regional level, SIRS targets provide substantiated recommendations for regional decision makers to understand and work towards mitigating the negative effects of climate change for Siberia and its population. This approach will allow the Siberian Branch of the Russian National Committee for IGBP to perform its mission, ensuring the growth of scientific knowledge of the dynamic Siberian environment and its subsystems, and to develop a solid basis for mitigation and adaptation strategies for the negative consequences of global change. 1 For example, 'Complex monitoring of the Great Vasyugan Bog: modern state and development processes investigations' and 'Ecological problems of Siberian cities'. 2 For example, 'Models of biosphere change based on the boreal ecosystems' carbon balance using field and satellite data observations' and 'Information technologies, mathematical models and methods for monitoring and control of ecosystems intended for stationary, mobile and remote observations'. 3 'Environmental observations, modeling and information systems' (http://enviromis.scert.ru/) and 'Man-induced environmental risks: monitoring, management and mitigation of man-made changes in Siberia (Enviro-RISKS)'. References [1] Brasseur G 2003 IGBP Newsletter No 50 (June 2002) IGBP II - Special Edition Issue 3rd IGBP Congress Overview Global Change Newsletter No 55 pp 2-4 [2] 2005 Bulletin of the Russian National Committee for the International Geosphere Biosphere Programme 4 [3] Ippolitov I I, Kabanov M V, Komarov A I and Kuskov A I 2004 Patterns of modern natural-climatic changes in Siberia: observed changes of annual temperature and pressure Geogr. Nat. Resources 3 90-6 [4] Volodin E M and Dianskii N A 2003 Response of a coupled atmosphere-ocean general circulation model to increased carbon dioxide Izvestiya, Atmospheric and Oceanic Physics 239 170-86 [5] Groisman P Y et al 2009 The Northern Eurasia Earth Science Partnership: an example of science applied to societal needs Bull. Am. Meteorol. Soc. 90 671-88 [6] Shiklomanov and Lammers R L 2009 Record Russian river discharge in 2007 and the limits of analysis Environ. Res. Lett. 4 045015 [7] Tchebakova N M, Parfenova E and Soja A J 2009 The effects of climate, permafrost and fire on vegetation change in Siberia in a changing climate Environ. Res. Lett. 4 045013 [8] Soja A et al 2007 Climate-induced boreal forest change: predictions versus current observations Global Planet. Change 56 274-96 [9] Groisman P Y and Bartalev S V 2007 Northern Eurasia Earth Science Partnership Initiative (NEESPI): science plan overview Global Planet. Change 56 215-34 [10] Gordov E P and Begni G 2005 Siberia integrated regional study development Comput. Technol. 10 149-55 [11] Gordov E P, Begni G, Heiman M, Kabanov M V, Lykossov V N, Shvidenko A Z and Vaganov E A 2006 Siberia integrated regional study as a basis for international scientific cooperation Comput. Technol. 11 16-28 [12] Baklanov A and Gordov E P 2006 Man-induced environmental risks: monitoring, management and remediation of man-made changes in Siberia Comput. Technol. 11 162-71 [13] Gordov E P 2004 Computational and information technologies for environmental sciences Comput. Technol. 9 3-10 Gordov E P 2004 Modern tendencies in regional environmental studies Geogr. Nat. Resources. (special issue) 11-18 Akhlyostin A Yu and Fazliev A Z 2003 Software for presentation of scientific information in the framework of a WEB portal Proc. SPIE 5396 111-8 Gordov E P, De Rudder A, Lykosov V N, Fazliev A Z and Fedra K 2004 Web-portal ATMOS as basis for integrated investigations of Siberia environment Comput. Technol. 9 3-13 Gordov E P, Lykosov V N and Fazliev A Z 2006 Web portal on environmental sciences 'ATMOS' Adv. Geosci. 8 33-8 Okladnikov I G and Titov A G 2006 Web-system for processing and visualization of meteorological data Environmental Observations, Modeling and Information Systems ed E P Gordov (Tomsk: Tomsk CSTI) 42 pp Gordov E P, Okladnikov I G and Titov A G 2007 Development of elements of a web-based information-computational system for studies of regional environment processes Comput. Technol. 12 20-8 Okladnikov I G, Titov A G, Melnikova V N and Shulgina T M 2008 Web-system for processing and visualization of meteorological and climatic data Comput. Technol. 13 64-9 Titov A G, Gordov E P, Okladnikov I G and Shulgina N M 2009 Web-system for processing and visualization of meteorological data for Siberian environment research International J. Digital Earth 2 105-19 Gordov E P and Lykossov V N 2007 Development of information-computational infrastructure for integrated study of Siberia environment Comput. Technol. 12 19-30 [14] Shokin Y I and Fedotov A M 2003 Integration of informational and telecommunicational resources of Siberian Branch of RAS Comput. Technol. 8 161-71 [15] Gordov E P, Kabanov M V and Lykossov V N 2006 Information-computational technologies for environmental science: young scientists training Comput. Technol. 11 3-15 Gordov E P and Lykossov V N 2008 ICT for environmental sciences: synthesis of science and education Comput. Technol. 13 3-11 [16] Baklanov A A and Gordov E P (eds) 2008 Enviro-RISKS: man-induced environmental risks: monitoring, management and remediation of man-made changes in Siberia. Final Scientific Report of EC 6FP CA Enviro-RISKS Project DMI Scientific Report 08-05 Copenhagen (ISBN: 978-87-7478-571-2) Four volumes available at www.dmi.dk/dmi/sr08-05-1.pdf, www.dmi.dk/dmi/sr08-052.pdf, www.dmi.dk/dmi/sr08-05-3.pdf and www.dmi.dk/dmi/sr08-05-4.pdf [17] Kobysheva N V (ed) 2001 Klimat Rossii (St Petersburg: Gidrometizdat) p 665 [18] Ippolitov I I, Kabanov M V and Loginov S V 2007 Spatiotemporal scales of warming observed in Siberia Reports of the Russian Academy of Sciences/Earth Science Section 413 248-51 [19] Shulgina T M, Genina E Yu, Gordov E P and Nikitchuk K 2009 Comparative analysis of atmosphere temperature variability for Northern Eurasia based on the reanalysis and in-situ observed data Geophys. Res. Abs. 11 EGU2009-880 [20] Kozlova E A, Manning A C, Kisilyakhov Y, Seifert T and Heimann M 2008 Seasonal, synoptic, and diurnal-scale variability of biogeochemical trace gases and O2 from a 300-m tall tower in central Siberia Global Biogeochem. Cycles 22 GB4020

Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types.

PubMed Central

Satoh, T; Fantl, W J; Escobedo, J A; Williams, L T; Kaziro, Y

1993-01-01

A series of pieces of evidence have shown that Ras protein acts as a transducer of the platelet-derived growth factor (PDGF) receptor-mediated signaling pathway: (i) formation of Ras.GTP is detected immediately on PDGF stimulation, and (ii) a dominant inhibitory mutant Ras, as well as a neutralizing anti-Ras antibody, can interfere with PDGF-induced responses. On the other hand, several signal transducing molecules including phosphatidylinositol 3-kinase (PI3-K), GTPase-activating protein (GAP), and phospholipase C gamma (PLC gamma) bind directly to the PDGF receptor and become tyrosine phosphorylated. Recently, it was shown that specific phosphorylated tyrosines of the PDGF receptor are responsible for interaction between the receptor and each signaling molecule. However, the roles of these signaling molecules have not been elucidated, and it remains unclear which molecules are implicated in the Ras pathway. In this study, we measured Ras activation in cell lines expressing mutant PDGF receptors that are deficient in coupling with specific molecules. In fibroblast CHO cells, a mutant receptor (Y708F/Y719F [PI3-K-binding sites]) was unable to stimulate Ras, whereas another mutant (Y739F [the GAP-binding site]) could do so, suggesting an indispensable role of PI3-K or a protein that binds to the same sites as PI3-K for PDGF-stimulated Ras activation. By contrast, both of the above mutants were capable of stimulating Ras protein in a pro-B-cell line, BaF3. Furthermore, a mutant receptor (Y977F/Y989F [PLC gamma-binding sites]) could fully activate Ras, and the direct activation of protein kinase C and calcium mobilization had almost no effect on the GDP/GTP state of Ras in this cell line. These results suggest that, in the pro-B-cell transfectants, each of the above pathways (PI3-K, GAP, and PLC gamma) can be eliminated without a loss of Ras activation. It remains unclear whether another unknown essential pathway which regulates Ras protein exists within BaF3 cells. Therefore, it is likely that several different PDGF receptor-mediated signaling pathways function upstream of Ras, and the extent of the contribution of each pathway for the regulation of Ras may differ among different cell types. Images PMID:8388543

The Intracrine Renin-Angiotensin System

PubMed Central

Kumar, Rajesh; Thomas, Candice M.; Yong, Qian Chen; Chen, Wen; Baker, Kenneth M.

2014-01-01

The renin-angiotensin system (RAS) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, angiotensin (Ang) II, is neither synthesized in, nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate the function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is further enhanced by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The current review presents a synopsis of the literature on this system in different tissues. PMID:22590974

Society News: PhD theses could win prizes; Last chance for IYA2009 grants; New Fellows; RAS Fellows win prizes; Need a job? Need staff? RAS Library Saturdays

NASA Astrophysics Data System (ADS)

2009-08-01

Fellows who are PhD student supervisors should be on the lookout for exceptionally good work from research students submitting their theses this year, for nomination for the RAS Michael Penston Astronomy Prize and the RAS Keith Runcorn Prize. The RAS is offering one last chance to apply for grants towards International Year of Astronomy activities, but you'll have to apply soon. The Society sends congratulations to Fellows of the RAS who have recently received prestigious awards for their work.

Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pair motions

NASA Astrophysics Data System (ADS)

Vatansever, Sezen; Gümüş, Zeynep H.; Erman, Burak

2016-11-01

K-Ras is the most frequently mutated oncogene in human cancers, but there are still no drugs that directly target it in the clinic. Recent studies utilizing dynamics information show promising results for selectively targeting mutant K-Ras. However, despite extensive characterization, the mechanisms by which K-Ras residue fluctuations transfer allosteric regulatory information remain unknown. Understanding the direction of information flow can provide new mechanistic insights for K-Ras targeting. Here, we present a novel approach -conditional time-delayed correlations (CTC) - using the motions of all residue pairs of a protein to predict directionality in the allosteric regulation of the protein fluctuations. Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Furthermore, our study is the first to identify driver-follower relationships in correlated motions of K-Ras residue pairs, revealing the direction of information flow during allosteric modulation of its nucleotide-dependent intrinsic activity: active K-Ras Switch-II region motions drive Switch-I region motions, while α-helix-3L7 motions control both. Our results provide novel insights for strategies that directly target mutant K-Ras.

The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting.

PubMed

Jonckheere, Nicolas; Vasseur, Romain; Van Seuningen, Isabelle

2017-03-01

RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence. In this review, we discuss the central role of K-RAS mutations and their tremendous diversity of biological properties by the interconnected regulation of signaling pathways (MAPKs, NF-κB, PI3K, Ral…). In pancreatic ductal adenocarcinoma, transcriptome analysis and preclinical animal models showed that K-RAS mutation alters biological behavior of PDAC cells (promoting proliferation, migration and invasion, evading growth suppressors, regulating mucin pattern, and miRNA expression). K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming. Finally we discuss therapeutic targeting strategies of K-RAS that have been developed without significant clinical success so far. As K-RAS is considered as the undruggable target, targeting its multiple effectors and target genes should be considered as potential alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

PubMed Central

Radziwill, G.; Erdmann, R. A.; Margelisch, U.; Moelling, K.

2003-01-01

The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. PMID:12808105

Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye.

PubMed

Wu, Yue; Zhuang, Yuan; Han, Min; Xu, Tian; Deng, Kejing

2009-10-20

Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, rasKP, which causes excessive apoptosis in the Drosophila eye. This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress rasKP-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the rasKP cell death. In addition, we find a strong correlation between rasKP-induced apoptosis in the eye disc and the activation of JNK signalling. In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression.

Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation

PubMed Central

Song, Kun; Zhang, Jian; Lu, Shaoyong

2017-01-01

Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras-mediated signaling pathway, but its efficacy is reduced by R135K mutation in H-Ras. However, the detailed mechanism is unresolved. Here, using molecular dynamics (MD) simulations and dynamic network analysis, we explored the molecular mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying allosteric network in H-Ras. MD simulations revealed that the overall structures of the two complexes did not change significantly, but the H-Ras–NS1 interface underwent significant conformational alteration in the mutant Binding free energy analysis showed that NS1 binding was unfavored after R135K mutation, which resulted in the unfavorable binding of NS1. Furthermore, the critical residues on H-Ras responsible for the loss of binding of NS1 were identified. Importantly, the allosteric networks for these important residues were revealed, which yielded a novel insight into the allosteric regulatory mechanism of H-Ras. PMID:29072601

The objective measurement of physical activity and sedentary behaviour in 2-3 year olds and their parents: a cross-sectional feasibility study in the bi-ethnic Born in Bradford cohort.

PubMed

Costa, Silvia; Barber, Sally E; Cameron, Noël; Clemes, Stacy A

2015-11-11

The reported lower physical activity (PA) levels of British South Asians (SA) are suggested as a key influence in their increased risk of non-communicable diseases compared to their White British peers. Differences in objectively measured PA and sedentary behaviour (SB) between these ethnic groups have been observed during childhood (ages: 8-10 years). However, no information exists on objectively measured PA/SB in younger children, or how early in life differences in these behaviours emerge. Assessing PA/SB in the Born in Bradford (BIB) cohort study provides an opportunity to address such gaps in the literature, but previous studies have found recruiting and retaining SA participants challenging, and the feasibility of using accelerometers with SA children and parents is unknown. This study investigated the feasibility of recruiting and objectively measuring the habitual PA/SB of 2-3 year old SA and White British children and parents from the BIB study. Families were informed about the study during routine BIB assessments. Consenting families were visited at home for anthropometry measurements, interviews, material delivery and collection. Participants (child and parents) were instructed to wear the ActiGraph GT3X+ for 8 days. Descriptive statistics were computed, and ethnic differences tested (Chi-square) for recruitment uptake and compliance. 160 families (30 % SA) provided contact details, and 97 (22 % SA) agreed to enter the study. White British families showed lower refusal and higher intake into the study than SA (p = 0.006). Of 89 children issued with an accelerometer, 34 % complied with the 8-day protocol (significantly less SA; p = 0.015) and 75 % provided enough days (≥ 3) to assess habitual PA/SB (no ethnic differences). Parental rates of compliance with the protocol did not differ between ethnicities. Issues experienced with the protocol and accelerometer use, and successful implementation strategies/procedures are presented. Although greater efforts may be required to recruit SA, those consenting to participate were as likely as White British to provide enough data to assess habitual PA/SB. The issues and successful strategies reported in this feasibility study represent valuable information for planning future studies, and enhance recruitment and compliance with accelerometer protocols in SA and White British toddlers and parents.

Impact of physical activity, sedentary behaviour and muscle strength on bone stiffness in 2-10-year-old children-cross-sectional results from the IDEFICS study.

PubMed

Herrmann, Diana; Buck, Christoph; Sioen, Isabelle; Kouride, Yiannis; Marild, Staffan; Molnár, Dénes; Mouratidou, Theodora; Pitsiladis, Yannis; Russo, Paola; Veidebaum, Toomas; Ahrens, Wolfgang

2015-09-17

Physical activity (PA), weight-bearing exercises (WBE) and muscle strength contribute to skeletal development, while sedentary behaviour (SB) adversely affects bone health. Previous studies examined the isolated effect of PA, SB or muscle strength on bone health, which was usually assessed by x-ray methods, in children. Little is known about the combined effects of these factors on bone stiffness (SI) assessed by quantitative ultrasound. We investigated the joint association of PA, SB and muscle strength on SI in children. In 1512 preschool (2- < 6 years) and 2953 school children (6-10 years), data on calcaneal SI as well as on accelerometer-based sedentary time (SED), light (LPA), moderate (MPA) and vigorous PA (VPA) were available. Parents reported sports (WBE versus no WBE), leisure time PA and screen time of their children. Jumping distance and handgrip strength served as indicators for muscle strength. The association of PA, SB and muscle strength with SI was estimated by multivariate linear regression, stratified by age group. Models were adjusted for age, sex, country, fat-free mass, daylight duration, consumption of dairy products and PA, or respectively SB. Mean SI was similar in preschool (79.5 ± 15.0) and school children (81.3 ± 12.1). In both age groups, an additional 10 min/day in MPA or VPA increased the SI on average by 1 or 2%, respectively (p ≤ .05). The negative association of SED with SI decreased after controlling for MVPA. LPA was not associated with SI. Furthermore, participation in WBE led to a 3 and 2% higher SI in preschool (p = 0.003) and school children (p < .001), respectively. Although muscle strength significantly contributed to SI, it did not affect the associations of PA with SI. In contrast to objectively assessed PA, reported leisure time PA and screen time showed no remarkable association with SI. This study suggests that already an additional 10 min/day of MPA or VPA or the participation in WBE may result in a relevant increase in SI in children, taking muscle strength and SB into account. Our results support the importance of assessing accelerometer-based PA in large-scale studies. This may be important when deriving dose-response relationships between PA and bone health in children.

Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway.

PubMed

Jang, Ja-Young; Hong, Young June; Lim, Junsup; Choi, Jin Sung; Choi, Eun Ha; Kang, Seongman; Rhim, Hyangshuk

2018-02-01

Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O 2 - ) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O 2 - dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using HEC-RAS to Enhance Interpretive Capabilities of Geomorphic Assessments

NASA Astrophysics Data System (ADS)

Keefer, L. L.

2005-12-01

The purpose of a geomorphic assessment is to characterize and evaluate a fluvial system for determining the past watershed and channel conditions, current geomorphic character and potential future channel adjustments. The geomorphic assessment approach utilized by the Illinois State Water Survey assesses channel response to disturbance at multiple temporal and spatial scales to help identify the underlying factors and events which led to the existing channel morphology. This is accomplished through two phases of investigation that involve a historical and physical analysis of the watershed, disturbance history, and field work at increasing levels of detail. To infer future channel adjustments, the geomorphic assessment protocol combines two methods of analyses that are dependent on the quantity and detail of the available data. The first method is the compilation of multiple lines of evidence using qualitative information related to the dominant fluvial environment, channel gradient, stream power thresholds, and channel evolution models. The second method is the use of hydraulic models which provide additional interpretative skills to evaluate potential channel adjustments. The structured data collection framework of the geomorphic assessment approach is used for the development of a HEC-RAS model. The model results are then used as another tool to determine the influence of bridges and control structures on channel stability, stream power profiles to identify potential channel bed degradation zones, and provide data for physically-based bank stability models. This poster will demonstrate the advantages of using a hydraulic model, such as HEC-RAS, to expand the interpretive capabilities of geomorphic assessments. The results from applying this approach will be demonstrated for the Big Creek watershed of the Cache River Basin in southern Illinois.

Effects of the iodine incorporation on the structure and physical properties of Ge-Sb-Se chalcogenide glasses

NASA Astrophysics Data System (ADS)

Wang, Yaling; Xu, Junfeng; Cheng, Hu; Chang, Fang'e.; Jian, Zengyun

2018-01-01

(100-x)(Ge23Se67Sb10)-xI (x = 0, 3, 5, 7, 10 wt%) chalcohalide glasses were prepared by the traditional melt-quenched method. The structure and physical properties were analyzed by using XRD, TMA, FTIR and Vickers hardness tester. It was found that the glass structure trends to crystallization with increase of iodine content. The values of infrared transmittance decrease from 62% to 35% in the range of 2.5-16 μm with increasing iodine content. The density decreases from 4.62 ± 0.3 g cm-3 to 4.31 ± 0.3 g cm-3, the hardness decreases from 164.9 ± 0.5 kg mm-2 to 154.6 ± 0.5 kg mm-2. The glass transition point Tg decreases from 267 °C to 205 °C, while the thermal expansion coefficient increases with iodine content.

TAN-1813, a novel Ras-farnesyltransferase inhibitor produced by Phoma sp. taxonomy, fermentation, isolation and biological activities in vitro and in vivo.

PubMed

Ishii, T; Hayashi, K; Hida, T; Yamamoto, Y; Nozaki, Y

2000-08-01

A novel Ras-farnesyltransferase inhibitor designated TAN-1813 was isolated from the culture broth of a fungus strain, FL-41510, isolated as a plant endophyte. The producer was taxonomically characterized as Phoma sp. FL-41510. TAN-1813 inhibited rat brain farnesyltransferase and geranylgeranyltransferase I activity with IC50 values of 23 microg/ml and 47/microg/ml, respectively. TAN-1813 showed mixed-type inhibition with respect to farnesylpyrophosphate and noncompetitive inhibition with respect to a K-Ras C-terminal peptide. It also inhibited the in situ farnesylation of cellular Ras proteins in a K-ras transformant (NIH3T3/K-ras) of mouse embryonic fibroblast cell line NIH3T3. TAN- 1813 inhibited the proliferation of various human cancer cells, some of which harbor activated ras alleles, with IC50 values of 15 approximately 110 ng/ml as well as that of NIH3T3 and NIH3T3/K-ras cells with IC50S of 540 and 310 ng/ml, respectively. Flow cytometric analysis indicated that TAN-1813 arrests NIH3T3/K-ras cells at both G1 and G2/M phases of the cell cycle. In addition, TAN-1813 was found to induce morphological reversion of NIH3T3/K-ras cells from the transformed phenotype. Antitumor activity of TAN-1813 against human fibrosarcoma HT-1080 and NIH3T3/K-ras tumors in nude mice was also verified.

ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy.

PubMed

Teranishi, Junya; Yamamoto, Ryohei; Nagasawa, Yasuyuki; Shoji, Tatsuya; Iwatani, Hirotsugu; Okada, Noriyuki; Moriyama, Toshiki; Yamauchi, Atsushi; Tsubakihara, Yoshiharu; Imai, Enyu; Rakugi, Hiromi; Isaka, Yoshitaka

2015-09-01

Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did. © The Author(s) 2014.

Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, S.-H.; Wang, T.-H.; Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11227, Taiwan

2009-01-09

Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU {yields} GUU) at the GU dinucleotide while left the wild-type (WT)more » K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.« less

Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buhrman, Greg; O; #8242

2012-09-17

We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the 'off' and 'on' allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond themore » active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.« less

Synthesis and structural characterization of bulk Sb2Te3 single crystal

NASA Astrophysics Data System (ADS)

Sultana, Rabia; Gahtori, Bhasker; Meena, R. S.; Awana, V. P. S.

2018-05-01

We report the growth and characterization of bulk Sb2Te3 single crystal synthesized by the self flux method via solid state reaction route from high temperature melt (850˚C) and slow cooling (2˚C/hour) of constituent elements. The single crystal X-ray diffraction pattern showed the 00l alignment and the high crystalline nature of the resultant sample. The rietveld fitted room temperature powder XRD revealed the phase purity and rhombohedral structure of the synthesized crystal. The formation and analysis of unit cell structure further verified the rhombohedral structure composed of three quintuple layers stacked one over the other. The SEM image showed the layered directional growth of the synthesized crystal carried out using the ZEISS-EVOMA-10 scanning electron microscope The electrical resistivity measurement was carried out using the conventional four-probe method on a quantum design Physical Property Measurement System (PPMS). The temperature dependent electrical resistivity plot for studied Sb2Te3 single crystal depicts metallic behaviour in the absence of any applied magnetic field. The synthesis as well as the structural characterization of as grown Sb2Te3 single crystal is reported and discussed in the present letter.

Charge ordered insulating phases of DODHT salts with octahedral anions and a new radical salt, β''-(DODHT)2TaF6

NASA Astrophysics Data System (ADS)

Nishikawa, H.; Oshio, H.; Higa, M.; Kondo, R.; Kagoshima, S.; Nakao, A.; Sawa, H.; Yasuzuka, S.; Murata, K.

2008-10-01

Physical properties of isostructural β''-(DODHT)2X [DODHT = (l,4-dioxane-2,3-diyldithio)dihydrotetrathiafulvalene; X = PF6, AsF6, and SbF6] at ambient pressure have been compared. The insulating phase of β''-(DODHT)2PF6 salt has already been revealed to be a charge ordering (CO) state by X-ray diffraction study and magnetic behavior. CO in this salt was also confirmed by the observation of satellite reflections in oscillation photograph using synchrotron radiation. Transport property of β''-(DODHT)2SbF6 salt was reinvestigated up to the pressure of 3.7 GPa applied by a cubic anvil apparatus. Although the SbF6 salt turned to be metallic above 2.0 GPa, no superconductivity was observed. In order to examine the anion size dependence of DODHT salts with octahedral anions, we prepared a new DODHT salt, β''-(DODHT)2TaF6, which has the larger counter anion compared with the previous salts. Crystal structure of this salt was isostructural to the other DODHT salts. The electrical and magnetic properties of this salt were similar to those of β''-(DODHT)2SbF6 salt.

Inclusion of human mineralized exometabolites and fish wastes as a source of higher plant mineral nutrition in BTLSS mass exchange

NASA Astrophysics Data System (ADS)

Tikhomirova, Natalia; Tikhomirov, Alexander A.; Ushakova, Sofya; Anischenko, Olesya; Trifonov, Sergey V.

Human exometabolites inclusion into an intrasystem mass exchange will allow increasing of a closure level of a biological-technical life support system (BTLSS). Previously at the IBP SB RAS it was shown that human mineralized exometabolites could be incorporated in the BTLSS mass exchange as a mineral nutrition source for higher plants. However, it is not known how that combined use of human mineralized exometabolites and fish wastes in the capacity of nutrient medium, being a part of the BTLSS consumer wastes, will affect the plant productivity. Several wheat vegetations were grown in an uneven-aged conveyor on a neutral substrate. A mixture of human mineralized exometabolites and fish wastes was used as a nutrient solution in the experiment treatment and human mineralized exometabolites were used in the control. Consequently, a high wheat yield in the experiment treatment practically equal to the control yield was obtained. Thus, mineralized fish wastes can be an additional source of macro-and micronutrients for plants, and use of such wastes for the plant mineral nutrition allows increasing of BTLSS closure level.

An experimental study of the vortex wake at Mach number of 3

NASA Astrophysics Data System (ADS)

Shmakov, A. S.; Shevchenko, A. M.

2017-10-01

The results of experimental study of the flow in the wing wake at Mach number of 3 are presented. These experiments extends the data obtained in the same experimental setup at Mach numbers of 2.5 and 4 [1]. Experiments were carried out in supersonic wind tunnel T-325 of ITAM SB RAS. Rectangular half-wing with sharp edges with a chord length of 30 mm and semispan of 95 mm was used to generate vortex wake. Experimental data were obtained in two cross sections located 1.5 and 6 chord length downstream of the trailing edge at wing angle of attack of 10 degrees. Constant temperature hot-wire anemometer was used to measure disturbances in supersonic flow. Hot-wire aemometer was made of a tungsten wire with a diameter of 10 µm and length of 1.5 mm. Shlieren flow visualization were performed. As a result, the position and size of the vortex core in the wake of a rectangular wing were determined. For the first time mass flow distribution and its pulsations in the supersonic longitudinal vortex was measured at Mach number of 3.

Balanced RAP/RAS mix design and performance evaluation for project - specific service conditions.

DOT National Transportation Integrated Search

2013-01-01

This presentation summarizes Projects 0-6092/0-6614. It includes accomplishments, best practices, field performance data of RAP/RAS test sections, balanced RAP/RAS mix design for project-specific conditions, and approaches for improving RAP/RAS mix p...

RAS mutation prevalence among patients with metastatic colorectal cancer: a meta-analysis of real-world data.

PubMed

Kafatos, George; Niepel, Daniela; Lowe, Kimberley; Jenkins-Anderson, Sophie; Westhead, Hal; Garawin, Tamer; Traugottová, Zuzana; Bilalis, Antonios; Molnar, Edit; Timar, Jozsef; Toth, Erika; Gouvas, Nikolaos; Papaxoinis, George; Murray, Samuel; Mokhtar, Nadia; Vosmikova, Hana; Fabian, Pavel; Skalova, Alena; Wójcik, Piotr; Tysarowski, Andrzej; Barugel, Mario; van Krieken, J Han; Trojan, Jörg

2017-07-27

A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

Correlations between soil respiration and soil properties in sugarcane areas under green and slash-and-burn management systems

NASA Astrophysics Data System (ADS)

Rodrigo Panosso, Alan; Milori, Débora M. B. P.; Marques Júnior, José; Martin-Neto, Ladislau; La Scala, Newton, Jr.

2010-05-01

Soil management causes changes in soil physical, chemical, and biological properties that consequently affect its CO2 emission. In this work we studied soil respiration (FCO2) in areas with sugarcane production in southern Brazil under two different sugarcane management systems: green (G), consisting of mechanized harvesting that produces a large amount of crop residues left on the soil surface, and slash-and-burn (SB), in which the residues are burned before manual harvest, leaving no residues on the soil surface. The study was conducted after the harvest period in two side-by-side grids installed in adjacent areas, having 20 measurement points each. The objective of this work was to determinate whether soil physical and chemical properties within each plot were useful in order to explain the spatial variability of FCO2, supposedly influence by each management system. Most of the soil physical properties studied showed no significant differences between management systems, but on the other hand most of the chemical properties differed significantly when SB and G areas were compared. Total FCO2 was 31% higher in the SB plot (729 g CO2 m-2) when compared to the G plot (557 g CO2 m-2) throughout the 70-day period after harvest studied. This seems to be related to the sensitivity of FCO2 to precipitation events, as respiration in this plot increased significantly with increases in soil moisture. Despite temporal variability showed to be positively related to soil moisture, inside each management system there was a negative correlation (p<0.01) between the spatial changes of FCO2 and soil moisture (MS), R= -0.56 and -0.59 for G and SB respectively. There was no spatial correlation between FCO2 and soil organic matter in each management system, however, the humification index (Hum) of organic matter was negatively linear correlated with FCO2 in SB (R= -0.53, p<0.05) while positively linear correlated in G area (R=0.42, p<0.10). The multiple regression model analysis applied in each management system indicates that 63% of the FCO2 spatial variability in G managed could be explained by the model: FCO2(G)= 4.11978 -0.07672MS + 0.0045Hum +1.5352K -0.04474FWP, where K and FWP are potassium content and free water porosity in G area, respectively. On the other hand, 75% of FCO2 spatial variability in SB managed plot was accounted by the model: FCO2(SB) = 10.66774 -0.08624MS -0.02904Hum -2.42548K. Therefore, soil moisture, humification index of organic matter and potassium level were the main properties able to explain the spatial variability of FCO2 in both sugarcane management systems. This result indicates that changes in sugarcane management systems could result in changes on the soil chemical properties, mostly, especially humification index of organic matter. It seems that in conversion from slash-and-burn to green harvest system, free water porosity turns to be an important aspect in order to explain part of FCO2 spatial variability in green managed system.

Enzymatic and antisense effects of a specific anti-Ki-ras ribozyme in vitro and in cell culture.

PubMed Central

Giannini, C D; Roth, W K; Piiper, A; Zeuzem, S

1999-01-01

Due to their mode of action, ribozymes show antisense effects in addition to their specific cleavage activity. In the present study we investigated whether a hammerhead ribozyme is capable of cleaving mutated Ki-ras mRNA in a pancreatic carcinoma cell line and whether antisense effects contribute to the activity of the ribozyme. A 2[prime]-O-allyl modified hammerhead ribozyme was designed to cleave specifically the mutated form of the Ki- ras mRNA (GUU motif in codon 12). The activity was monitored by RT-PCR on Ki- ras RNA expression by determination of the relative amount of wild type to mutant Ki-ras mRNA, by 5-bromo-2[prime]-deoxy-uridine incorporation on cell proliferation and by colony formation in soft agar on malignancy in the human pancreatic adenocarcinoma cell line CFPAC-1, which is heterozygous for the Ki-ras mutation. A catalytically inactive ribozyme was used as control to differentiate between antisense and cleavage activity and a ribozyme with random guide sequences as negative control. The catalytically active anti-Ki-ras ribozyme was at least 2-fold more potent in decreasing cellular Ki-ras mRNA levels, inhibiting cell proliferation and colony formation in soft agar than the catalytically inactive ribozyme. The catalytically active anti-Ki-ras ribozyme, but not the catalytically inactive or random ribozyme, increased the ratio of wild type to mutated Ki-ras mRNA in CFPAC-1 cells. In conclusion, both cleavage activity and antisense effects contribute to the activity of the catalytically active anti-Ki-ras hammerhead ribozyme. Specific ribozymes might be useful in the treatment of pancreatic carcinomas containing an oncogenic GTT mutation in codon 12 of the Ki-ras gene. PMID:10373591

K-RAS(V12) Induces Autocrine Production of EGFR Ligands and Mediates Radioresistance Through EGFR-Dependent Akt Signaling and Activation of DNA-PKcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minjgee, Minjmaa; Toulany, Mahmoud; Kehlbach, Rainer

2011-12-01

Purpose: It is known that postirradiation survival of tumor cells presenting mutated K-RAS is mediated through autocrine activation of epidermal growth factor receptor (EGFR). In this study the molecular mechanism of radioresistance of cells overexpressing mutated K-RAS(V12) was investigated. Methods and Materials: Head-and-neck cancer cells (FaDu) presenting wild-type K-RAS were transfected with empty vector or vector expressing mutated K-RAS(V12). The effect of K-RAS(V12) on autocrine production of EGFR ligands, activation of EGFR downstream pathways, DNA damage repair, and postirradiation survival was analyzed. Results: Conditioned medium collected from K-RAS(V12)-transfected cells enhanced activation of the phosphatidylinositol-3-kinase-Akt pathway and increased postirradiation survival ofmore » wild-type K-RAS parental cells when compared with controls. These effects were reversed by amphiregulin (AREG)-neutralizing antibody. In addition, secretion of the EGFR ligands AREG and transforming growth factor {alpha} was significantly increased upon overexpression of K-RAS(V12). Expression of mutated K-RAS(V12) resulted in an increase in radiation-induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation at S2056. This increase was accompanied by increased repair of DNA double-strand breaks. Abrogation of DNA-PKcs phosphorylation by serum depletion or AREG-neutralizing antibody underscored the role of autocrine production of EGFR ligands, namely, AREG, in regulating DNA-PKcs activation in K-RAS mutated cells. Conclusions: These data indicate that radioresistance of K-RAS mutated tumor cells is at least in part due to constitutive production of EGFR ligands, which mediate enhanced repair of DNA double-strand breaks through the EGFR-phosphatidylinositol-3-kinase-Akt cascade.« less

The mucin MUC4 is a transcriptional and post-transcriptional target of K-ras oncogene in pancreatic cancer. Implication of MAPK/AP-1, NF-κB and RalB signaling pathways.

PubMed

Vasseur, Romain; Skrypek, Nicolas; Duchêne, Belinda; Renaud, Florence; Martínez-Maqueda, Daniel; Vincent, Audrey; Porchet, Nicole; Van Seuningen, Isabelle; Jonckheere, Nicolas

2015-12-01

The membrane-bound mucinMUC4 is a high molecularweight glycoprotein frequently deregulated in cancer. In pancreatic cancer, one of the most deadly cancers in occidental countries, MUC4 is neo-expressed in the preneoplastic stages and thereafter is involved in cancer cell properties leading to cancer progression and chemoresistance. K-ras oncogene is a small GTPase of the RAS superfamily, highly implicated in cancer. K-ras mutations are considered as an initiating event of pancreatic carcinogenesis and K-ras oncogenic activities are necessary components of cancer progression. However, K-ras remains clinically undruggable. Targeting early downstream K-ras signaling in cancer may thus appear as an interesting strategy and MUC4 regulation by K-ras in pancreatic carcinogenesis remains unknown. Using the Pdx1-Cre; LStopL-K-rasG12D mouse model of pancreatic carcinogenesis, we show that the in vivo early neo-expression of the mucin Muc4 in pancreatic intraepithelial neoplastic lesions (PanINs) induced by mutated K-ras is correlated with the activation of ERK, JNK and NF-κB signaling pathways. In vitro, transfection of constitutively activated K-rasG12V in pancreatic cancer cells led to the transcriptional upregulation of MUC4. This activation was found to be mediated at the transcriptional level by AP-1 and NF-κB transcription factors via MAPK, JNK and NF-κB pathways and at the posttranscriptional level by a mechanism involving the RalB GTPase. Altogether, these results identify MUC4 as a transcriptional and post-transcriptional target of K-ras in pancreatic cancer. This opens avenues in developing new approaches to target the early steps of this deadly cancer.

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy prior to resection of colorectal liver metastases

PubMed Central

Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M.; Andreou, Andreas; Cooper, Amanda B.; Kaur, Harmeet; Aloia, Thomas A.; Maru, Dipen M.; Vauthey, Jean-Nicolas

2014-01-01

Purpose RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. We sought to determine the association between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. Methods RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models including either radiologic morphologic response (model 1) or pathologic response (model 2). Results Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9% and 58.9%, respectively) than in patients with RAS mutations (10.5% and 36.8%; P =.006 and .015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response (odds ratio [OR], 4.38; 95% CI, 1.45-13.2) and major pathologic response (OR,2.79; 95% CI, 1.29-6.04). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.25 and 2.02, respectively, in model 1, and 3.19 and 2.23, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified prognosis in patients with inadequate response to preoperative chemotherapy. Conclusion RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy. PMID:25227306

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases.

PubMed

Zimmitti, Giuseppe; Shindoh, Junichi; Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M; Andreou, Andreas; Cooper, Amanda B; Kaur, Harmeet; Aloia, Thomas A; Maru, Dipen M; Vauthey, Jean-Nicolas

2015-03-01

RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2). Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy. RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.

K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology.

PubMed

Sakamoto, Kotaro; Kamada, Yusuke; Sameshima, Tomoya; Yaguchi, Masahiro; Niida, Ayumu; Sasaki, Shigekazu; Miwa, Masanori; Ohkubo, Shoichi; Sakamoto, Jun-Ichi; Kamaura, Masahiro; Cho, Nobuo; Tani, Akiyoshi

2017-03-11

Amino-acid mutations of Gly 12 (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH 2 ) as a consensus sequence. KRpep-2 showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K D and IC 50 values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH 2 ) that inhibited enzyme activity of K-Ras(G12D) with IC 50  = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naumov, Inna; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; Kazanov, Dina

2012-01-15

Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35-40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1more » and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our 'gene therapy' approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce {approx} 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by {approx} 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.« less

Sedentary behaviours among adults across Canada.

PubMed

Herman, Katya M; Saunders, Travis J

2016-12-27

 OBJECTIVES: While cross-Canada variations in physical activity and weight status have been illustrated, less is known about sedentary behaviour (SB). The aim of this study was to describe various SBs and their correlates among Canadian adults. METHODS: Cross-sectional data from the 2011-2012 Canadian Community Health Survey included 92,918 respondents aged 20-75+ years, representative of >22 million Canadian adults. TV/video viewing, computer, video game playing and reading time were self-reported. Associations with socio-demographic, health and health behaviour variables were examined. RESULTS: About 31% of adults reported >2 hours/day TV viewing, while 47% of men and 41% of women reported >5 hours/week computer use, 24% of men and 12% of women reported ≥1 hour/week video game playing, and 33% of men and 46% of women reported >5 hours/week reading; 28% of respondents reported ≥5 hours/day total SB time. Age was the strongest correlate: adults 75+ had 5 and 6 times greater odds respectively of reporting >2 hours/day TV viewing and >5 hours/week reading, but far lesser odds of reporting high computer or video game time, compared to adults 20-24. Other variables associated with specific SBs included gender, marital status, education, occupation, income and immigrant status, as well as BMI, weight perceptions, smoking, diet and physical activity. CONCLUSION: Common sedentary behaviours were associated with numerous socio-demographic, health and health behaviour characteristics in a large representative sample of Canadians. These correlates differed according to the type of SB. Public health interventions targeting SB should be behavior-specific and tailored to the population segment of interest.

Associations Between Maternal Mental Health and Well-being and Physical Activity and Sedentary Behavior in Children.

PubMed

Maher, Jaclyn P; Ra, Chaelin; OʼConnor, Sydney G; Belcher, Britni R; Leventhal, Adam; Margolin, Gayla; Dunton, Genevieve F

This study assessed whether aspects of maternal mental health and well-being were associated with objective monitor-based measures of child's physical activity (PA) and sedentary behavior (SB) and the extent to which household structure (i.e., single- vs multigenerational/dual-parent) and maternal employment (i.e., full-time vs not full-time) moderated those associations. Dyads (N = 191) of mothers and their 8- to 12-year-old children participated in the baseline wave of the Mother's and Their Children's Health study. Mothers (Mage = 40.9 yr [SD = 6.1]; 49% Hispanic) completed a battery of questionnaires to assess maternal mental health and well-being (i.e., self-esteem, life satisfaction, depressive symptoms, anxiety, perceived stress, parenting stress, financial stress, and life events stress). Children (Mage = 9.6 yr [SD = 0.9]; 54% Hispanic; 51% girls) wore an accelerometer across 1 week during waking hours to objectively measure moderate-to-vigorous PA (MVPA) and SB. In single-parent families (n = 47), but not multigenerational/dual-parent families, mothers' parenting stress was negatively associated with child's MVPA (β = -.34, p = .02). In corrected analyses, all other aspects of maternal mental health and well-being were not related to children's activity patterns. Parenting stress was the only maternal mental health variable associated with objective monitor-based measures of child's PA after adjusting for multiple comparisons. Results indicated weaker associations between maternal mental health and well-being and child's MVPA and SB than previously identified using subjective measures of behavior. Study findings support the need to use objective measurements of child's activity patterns to minimize potential confounding because of maternal report in evaluating child's PA and SB.

Ras mutations are rare in solitary cold and toxic thyroid nodules.

PubMed

Krohn, K; Reske, A; Ackermann, F; Müller, A; Paschke, R

2001-08-01

Activation of ras proto-oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules. To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules. To address the likelihood of a somatic mutation we also studied the clonal origin of these tumours. Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to verify sequencing results for the H-ras gene and to analyse the N-ras gene because its greater sensitivity in detecting somatic mutations. Clonality of nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR amplification of the human androgen receptor locus. Monoclonal origin was detectable in 14 of 23 informative samples from cold thyroid nodules. In toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules no ras mutation was detectable. Our study suggests that ras mutations are rare in solitary cold and toxic thyroid nodules and that the frequent monoclonal origin of these tumours implies somatic mutations in genes other than H-, K- and N-ras.

Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site.

PubMed

Mazhab-Jafari, Mohammad T; Marshall, Christopher B; Smith, Matthew J; Gasmi-Seabrook, Geneviève M C; Stathopulos, Peter B; Inagaki, Fuyuhiko; Kay, Lewis E; Neel, Benjamin G; Ikura, Mitsuhiko

2015-05-26

K-RAS4B (Kirsten rat sarcoma viral oncogene homolog 4B) is a prenylated, membrane-associated GTPase protein that is a critical switch for the propagation of growth factor signaling pathways to diverse effector proteins, including rapidly accelerated fibrosarcoma (RAF) kinases and RAS-related protein guanine nucleotide dissociation stimulator (RALGDS) proteins. Gain-of-function KRAS mutations occur frequently in human cancers and predict poor clinical outcome, whereas germ-line mutations are associated with developmental syndromes. However, it is not known how these mutations affect K-RAS association with biological membranes or whether this impacts signal transduction. Here, we used solution NMR studies of K-RAS4B tethered to nanodiscs to investigate lipid bilayer-anchored K-RAS4B and its interactions with effector protein RAS-binding domains (RBDs). Unexpectedly, we found that the effector-binding region of activated K-RAS4B is occluded by interaction with the membrane in one of the NMR-observable, and thus highly populated, conformational states. Binding of the RAF isoform ARAF and RALGDS RBDs induced marked reorientation of K-RAS4B from the occluded state to RBD-specific effector-bound states. Importantly, we found that two Noonan syndrome-associated mutations, K5N and D153V, which do not affect the GTPase cycle, relieve the occluded orientation by directly altering the electrostatics of two membrane interaction surfaces. Similarly, the most frequent KRAS oncogenic mutation G12D also drives K-RAS4B toward an exposed configuration. Further, the D153V and G12D mutations increase the rate of association of ARAF-RBD with lipid bilayer-tethered K-RAS4B. We revealed a mechanism of K-RAS4B autoinhibition by membrane sequestration of its effector-binding site, which can be disrupted by disease-associated mutations. Stabilizing the autoinhibitory interactions between K-RAS4B and the membrane could be an attractive target for anticancer drug discovery.

Impairment of K-Ras signaling networks and increased efficacy of epidermal growth factor receptor inhibitors by a novel synthetic miR-143.

PubMed

Akao, Yukihiro; Kumazaki, Minami; Shinohara, Haruka; Sugito, Nobuhiko; Kuranaga, Yuki; Tsujino, Takuya; Yoshikawa, Yuki; Kitade, Yukio

2018-05-01

Despite considerable research on K-Ras inhibitors, none had been established until now. We synthesized nuclease-resistant synthetic miR-143 (miR-143#12), which strongly silenced K-Ras, its effector signal molecules AKT and ERK, and the K-Ras activator Sos1. We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations. Cell growth was markedly suppressed in a concentration-dependent manner by miR-143#12 (IC 50 : 1.32 nmol L -1 ) with a decrease in the K-Ras mRNA level. Interestingly, this mRNA level was also downregulated by either a PI3K/AKT or MEK inhibitor, which indicates a positive circuit of K-Ras mRNA expression. MiR-143#12 silenced cytoplasmic K-Ras mRNA expression and impaired the positive circuit by directly targeting AKT and ERK mRNA. Combination treatment with miR-143#12 and a low-dose EGFR inhibitor induced a synergistic inhibition of growth with a marked inactivation of both PI3K/AKT and MAPK/ERK signaling pathways. However, silencing K-Ras by siR-KRas instead of miR-143#12 did not induce this synergism through the combined treatment with the EGFR inhibitor. Thus, miR-143#12 perturbed the K-Ras expression system and K-Ras activation by silencing Sos1 and, resultantly, restored the efficacy of the EGFR inhibitors. The in vivo results also supported those of the in vitro experiments. The extremely potent miR-143#12 enabled us to understand K-Ras signaling networks and shut them down by combination treatment with this miRNA and EGFR inhibitor in K-Ras-driven colon cancer cell lines. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Ras history

PubMed Central

2010-01-01

Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an intensive research effort to understand Ras protein structure, biochemistry and biology. While the ultimate goal has been developing anti-Ras drugs for cancer treatment, discoveries from Ras have laid the foundation for three broad areas of science. First, they focused studies on the origins of cancer to the molecular level, with the subsequent discovery of genes mutated in cancer that now number in the thousands. Second, elucidation of the biochemical mechanisms by which Ras facilitates signal transduction established many of our fundamental concepts of how a normal cell orchestrates responses to extracellular cues. Third, Ras proteins are also founding members of a large superfamily of small GTPases that regulate all key cellular processes and established the versatile role of small GTP-binding proteins in biology. We highlight some of the key findings of the last 28 years. PMID:21686117

Targeting RAS-driven human cancer cells with antibodies to upregulated and essential cell-surface proteins.

PubMed

Martinko, Alexander J; Truillet, Charles; Julien, Olivier; Diaz, Juan E; Horlbeck, Max A; Whiteley, Gordon; Blonder, Josip; Weissman, Jonathan S; Bandyopadhyay, Sourav; Evans, Michael J; Wells, James A

2018-01-23

While there have been tremendous efforts to target oncogenic RAS signaling from inside the cell, little effort has focused on the cell-surface. Here, we used quantitative surface proteomics to reveal a signature of proteins that are upregulated on cells transformed with KRAS G12V , and driven by MAPK pathway signaling. We next generated a toolkit of recombinant antibodies to seven of these RAS-induced proteins. We found that five of these proteins are broadly distributed on cancer cell lines harboring RAS mutations. In parallel, a cell-surface CRISPRi screen identified integrin and Wnt signaling proteins as critical to RAS-transformed cells. We show that antibodies targeting CDCP1, a protein common to our proteomics and CRISPRi datasets, can be leveraged to deliver cytotoxic and immunotherapeutic payloads to RAS-transformed cancer cells and report for RAS signaling status in vivo. Taken together, this work presents a technological platform for attacking RAS from outside the cell. © 2018, Martinko et al.

Deconstruction of the Ras switching cycle through saturation mutagenesis

PubMed Central

Bandaru, Pradeep; Shah, Neel H; Bhattacharyya, Moitrayee; Barton, John P; Kondo, Yasushi; Cofsky, Joshua C; Gee, Christine L; Chakraborty, Arup K; Kortemme, Tanja; Ranganathan, Rama; Kuriyan, John

2017-01-01

Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase activating protein and a nucleotide exchange factor. Removing the regulators shifts the distribution of mutational effects to be largely neutral, and reveals hotspots of activating mutations in residues that restrain Ras dynamics and promote the inactive state. Evolutionary analysis, combined with structural and mutational data, argue that Ras has co-evolved with its regulators in the vertebrate lineage. Overall, our results show that sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins. DOI: http://dx.doi.org/10.7554/eLife.27810.001 PMID:28686159

Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

PubMed Central

Driessen, Emma M.C.; van Roon, Eddy H.J.; Spijkers-Hagelstein, Jill A.P.; Schneider, Pauline; de Lorenzo, Paola; Valsecchi, Maria Grazia; Pieters, Rob; Stam, Ronald W.

2013-01-01

Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier results on the incidence of RAS mutations in Mixed Lineage Leukemia-rearranged acute lymphoblastic leukemia are inconclusive. Therefore, we studied frequencies and relation with clinical parameters of RAS mutations in a large cohort of infant acute lymphoblastic leukemia patients. Using conventional sequencing analysis, we screened neuroblastoma RAS viral (v-ras) oncogene homolog gene (NRAS), v-Ki-ras Kirsten rat sarcoma viral oncogene homolog gene (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) for mutations in a large cohort (n=109) of infant acute lymphoblastic leukemia patients and studied the mutations in relation to several clinical parameters, and in relation to Homeobox gene A9 expression and the presence of ALL1 fused gene 4-Mixed Lineage Leukemia (AF4-MLL). Mutations were detected in approximately 14% of all cases, with a higher frequency of approximately 24% in t(4;11)-positive patients (P=0.04). Furthermore, we identified RAS mutations as an independent predictor (P=0.019) for poor outcome in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia, with a hazard ratio of 3.194 (95% confidence interval (CI):1.211–8.429). Also, RAS-mutated infants have higher white blood cell counts at diagnosis (P=0.013), and are more resistant to glucocorticoids in vitro (P<0.05). Finally, we demonstrate that RAS mutations, and not the lack of Homeobox gene A9 expression nor the expression of AF4-MLL are associated with poor outcome in t(4;11)-rearranged infants. We conclude that the presence of RAS mutations in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia is an independent predictor for a poor outcome. Therefore, future risk-stratification based on abnormal RAS-pathway activation and RAS-pathway inhibition could be beneficial in RAS-mutated infant acute lymphoblastic leukemia patients. PMID:23403319

Synthetic lipopeptide inhibitors of RAS oncoproteins | NCI Technology Transfer Center | TTC

Cancer.gov

It is well known that overactive Ras signaling is linked to many forms of cancer, and despite intensive efforts worldwide to develop effective inhibitors of Ras, to date there is no anti-Ras inhibitor in clinical use. Researchers at the NCI’s Cancer and Inflammation Program, in collaboration with scientists at Vanderbilt University and the University of Illinois in Chicago, have identified a number of small peptidomimetic compounds that bind to Ras proteins with nanomolar affinity. NCI’s Cancer and Inflammation Program seeks partners interested in licensing or co-development of synthetic, highly potent cell-permeable inhibitors of Ras that bind to the protein directly.

Computational representation and hemodynamic characterization of in vivo acquired severe stenotic renal artery geometries using turbulence modeling.

PubMed

Kagadis, George C; Skouras, Eugene D; Bourantas, George C; Paraskeva, Christakis A; Katsanos, Konstantinos; Karnabatidis, Dimitris; Nikiforidis, George C

2008-06-01

The present study reports on computational fluid dynamics in the case of severe renal artery stenosis (RAS). An anatomically realistic model of a renal artery was reconstructed from CT scans, and used to conduct CFD simulations of blood flow across RAS. The recently developed shear stress transport (SST) turbulence model was pivotally applied in the simulation of blood flow in the region of interest. Blood flow was studied in vivo under the presence of RAS and subsequently in simulated cases before the development of RAS, and after endovascular stent implantation. The pressure gradients in the RAS case were many orders of magnitude larger than in the healthy case. The presence of RAS increased flow resistance, which led to considerably lower blood flow rates. A simulated stent in place of the RAS decreased the flow resistance at levels proportional to, and even lower than, the simulated healthy case without the RAS. The wall shear stresses, differential pressure profiles, and net forces exerted on the surface of the atherosclerotic plaque at peak pulse were shown to be of relevant high distinctiveness, so as to be considered potential indicators of hemodynamically significant RAS.

Comparative Capabilities of Clinical Assessment, Diagnostic Criteria, and Polysomnography in Detecting Sleep Bruxism

PubMed Central

Palinkas, Marcelo; De Luca Canto, Graziela; Rodrigues, Laíse Angélica Mendes; Bataglion, César; Siéssere, Selma; Semprini, Marisa; Regalo, Simone Cecilio Hallak

2015-01-01

Objective: To evaluate the diagnostic capability of signs and symptoms of sleep bruxism (SB) as per the American Academy of Sleep Medicine (AASM) criteria and a diagnostic grading system proposed by international experts for assessing SB. Methods: The study was conducted in three phases (interview, physical examination, and sleep studies). Subjects were asked about self-reported tooth grinding sounds occurring during sleep, muscle fatigue, temporal headaches, jaw muscle pain, and jaw locking. A visual examination was conducted to check for presence of abnormal tooth wear. A full-night polysomnography (PSG) was performed. After three phases, the subjects were divided into two groups matched by age and gender: Case Group, 45 SB subjects, and Control Group, 45 non-SB subjects. Diagnostic accuracy measurements were calculated for each sign or symptom individually and for the two diagnostic criteria analyzed. Results: Muscle fatigue, temporal headaches, and AASM criteria were associated with highest sensitivity (78%, 67%, 58%, respectively) and also with highest diagnostic odds ratio (OR = 9.63, 9.25, 6.33, respectively). Jaw locking, muscle pain, and the criterion of “probable SB” were associated with the worst sensitivity (16%, 18%, 22%, respectively). Conclusions: Presence of muscle fatigue and temporal headaches can be considered good tools to screen SB patients. None of the diagnostic criteria evaluated was able to accurately identify patients with SB. AASM criteria had the strongest diagnostic capabilities and—although they do not attain diagnostic values high enough to replace the current gold standard (PSG)—should be used as a screening tool to identify SB. Citation: Palinkas M, De Luca Canto G, Rodrigues LA, Bataglion C, Siéssere S, Semprini M, Regalo SC. Comparative capabilities of clinical assessment, diagnostic criteria, and polysomnography in detecting sleep bruxism. J Clin Sleep Med 2015;11(11):1319–1325. PMID:26235152

The Influence of Weather Variation, Urban Design and Built Environment on Objectively Measured Sedentary Behaviour in Children

PubMed Central

Katapally, Tarun Reddy; Rainham, Daniel; Muhajarine, Nazeem

2016-01-01

With emerging evidence indicating that independent of physical activity, sedentary behaviour (SB) can be detrimental to health, researchers are increasingly aiming to understand the influence of multiple contexts such as urban design and built environment on SB. However, weather variation, a factor that continuously interacts with all other environmental variables, has been consistently underexplored. This study investigated the influence of diverse environmental exposures (including weather variation, urban design and built environment) on SB in children. This cross-sectional observational study is part of an active living research initiative set in the Canadian prairie city of Saskatoon. Saskatoon's neighbourhoods were classified based on urban street design into grid-pattern, fractured grid-pattern and curvilinear types of neighbourhoods. Diverse environmental exposures were measured including, neighbourhood built environment, and neighbourhood and household socioeconomic environment. Actical accelerometers were deployed between April and June 2010 (spring-summer) to derive SB of 331 10–14 year old children in 25 one week cycles. Each cycle of accelerometry was conducted on a different cohort of children within the total sample. Accelerometer data were matched with localized weather patterns derived from Environment Canada weather data. Multilevel modeling using Hierarchical Linear and Non-linear Modeling software was conducted by factoring in weather variation to depict the influence of diverse environmental exposures on SB. Both weather variation and urban design played a significant role in SB. After factoring in weather variation, it was observed that children living in grid-pattern neighbourhoods closer to the city centre (with higher diversity of destinations) were less likely to be sedentary. This study demonstrates a methodology that could be replicated to integrate geography-specific weather patterns with existing cross-sectional accelerometry data to understand the influence of urban design and built environment on SB in children. PMID:29546188

Enhancement of electron correlation due to the molecular dimerization in organic superconductors β -(BDA-TTP )2X (X =I3, SbF6)

NASA Astrophysics Data System (ADS)

Aizawa, Hirohito; Kuroki, Kazuhiko; Yamada, Jun-ichi

2015-10-01

We perform a first-principles band calculation for quasi-two-dimensional organic superconductors β -(BDA -TTP) 2I3 and β -(BDA -TTP) 2SbF6. The first-principles band structures between the I3 and SbF6 salts are apparently different. We construct a tight-binding model for each material which accurately reproduces the first-principles band structure. The obtained transfer energies give the differences as follows: (i) larger dimerization in the I3 salt than the SbF6 salt, and (ii) different signs and directions of the interstacking transfer energies. To decompose the origin of the difference into the dimerization and the interstacking transfer energies, we adopt a simplified model by eliminating the dimerization effect and focus only on the difference caused by the interstacking transfer energies. From the analysis using the simplified model, we find that the difference of the band structure comes mainly from the strength of the dimerization. To compare the strength of the electron correlation having roots in the band structure, we calculate the physical properties originating from the effect of the electron correlation such as the spin susceptibility applying the two-particle self-consistent method. We find that the maximum value of the spin susceptibility for the I3 salt is larger than that of the SbF6 salt. Hypothetically decreasing the dimerization within the model of the I3 salt, the spin susceptibility takes almost the same value as that of the SbF6 salt for the same magnitude of the dimerization. We expect that the different ground state between the I3 and SbF6 salt mainly comes from the strength of the dimerization which is apparently masked in the band calculation along a particular k path.

The Gaia-ESO Survey: double-, triple-, and quadruple-line spectroscopic binary candidates

NASA Astrophysics Data System (ADS)

Merle, T.; Van Eck, S.; Jorissen, A.; Van der Swaelmen, M.; Masseron, T.; Zwitter, T.; Hatzidimitriou, D.; Klutsch, A.; Pourbaix, D.; Blomme, R.; Worley, C. C.; Sacco, G.; Lewis, J.; Abia, C.; Traven, G.; Sordo, R.; Bragaglia, A.; Smiljanic, R.; Pancino, E.; Damiani, F.; Hourihane, A.; Gilmore, G.; Randich, S.; Koposov, S.; Casey, A.; Morbidelli, L.; Franciosini, E.; Magrini, L.; Jofre, P.; Costado, M. T.; Jeffries, R. D.; Bergemann, M.; Lanzafame, A. C.; Bayo, A.; Carraro, G.; Flaccomio, E.; Monaco, L.; Zaggia, S.

2017-12-01

Context. The Gaia-ESO Survey (GES) is a large spectroscopic survey that provides a unique opportunity to study the distribution of spectroscopic multiple systems among different populations of the Galaxy. Aims: Our aim is to detect binarity/multiplicity for stars targeted by the GES from the analysis of the cross-correlation functions (CCFs) of the GES spectra with spectral templates. Methods: We developed a method based on the computation of the CCF successive derivatives to detect multiple peaks and determine their radial velocities, even when the peaks are strongly blended. The parameters of the detection of extrema (DOE) code have been optimized for each GES GIRAFFE and UVES setup to maximize detection. The DOE code therefore allows to automatically detect multiple line spectroscopic binaries (SBn, n ≥ 2). Results: We apply this method on the fourth GES internal data release and detect 354 SBn candidates (342 SB2, 11 SB3, and even one SB4), including only nine SBs known in the literature. This implies that about 98% of these SBn candidates are new because of their faint visual magnitude that can reach V = 19. Visual inspection of the SBn candidate spectra reveals that the most probable candidates have indeed a composite spectrum. Among the SB2 candidates, an orbital solution could be computed for two previously unknown binaries: CNAME 06404608+0949173 (known as V642 Mon) in NGC 2264 and CNAME 19013257-0027338 in Berkeley 81 (Be 81). A detailed analysis of the unique SB4 (four peaks in the CCF) reveals that CNAME 08414659-5303449 (HD 74438) in the open cluster IC 2391 is a physically bound stellar quadruple system. The SB candidates belonging to stellar clusters are reviewed in detail to discard false detections. We suggest that atmospheric parameters should not be used for these system components; SB-specific pipelines should be used instead. Conclusions: Our implementation of an automatic detection of spectroscopic binaries within the GES has allowed the efficient discovery of many new multiple systems. With the detection of the SB1 candidates that will be the subject of a forthcoming paper, the study of the statistical and physical properties of the spectroscopic multiple systems will soon be possible for the entire GES sample. Based on data products from observations made with ESO Telescopes at the La Silla Paranal Observatory under programme ID 188.B-3002. These data products have been processed by the Cambridge Astronomy Survey Unit (CASU) at the Institute of Astronomy, University of Cambridge, and by the FLAMES/UVES reduction team at INAF/Osservatorio Astrofisico di Arcetri. These data have been obtained from the Gaia-ESO Survey Data Archive, prepared and hosted by the Wide Field Astronomy Unit, Institute for Astronomy, University of Edinburgh, which is funded by the UK Science and Technology Facilities Council.

Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia

PubMed Central

Oshima, Koichi; Khiabanian, Hossein; da Silva-Almeida, Ana C.; Tzoneva, Gannie; Abate, Francesco; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Carpenter, Zachary; Penson, Alex; Perez-Garcia, Arianne; Eckert, Cornelia; Nicolas, Concepción; Balbin, Milagros; Sulis, Maria Luisa; Kato, Motohiro; Koh, Katsuyoshi; Paganin, Maddalena; Basso, Giuseppe; Gastier-Foster, Julie M.; Devidas, Meenakshi; Loh, Mignon L.; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A.

2016-01-01

Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID:27655895

[Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

PubMed

Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

2016-11-20

To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (P<0.05). In EOC tissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (P<0.05) and was the highest in serous cystadenomcarcinoma; Sos1 expression did not show significant correlation with the clinicopathological indexes of the patients. High expressions of both Ras and Sos1 proteins were associated with shorter progression-free survival of the patients, but this association was not statistically significant. Ras and Sos1 protein may participate in in the occurrence and development of EOC. The tissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

Temporal dissection of K-ras(G12D) mutant in vitro and in vivo using a regulatable K-ras(G12D) mouse allele.

PubMed

Wang, Zuoyun; Feng, Yan; Bardeesy, Nabeel; Bardessy, Nabeel; Wong, Kwok-Kin; Liu, Xin-Yuan; Ji, Hongbin

2012-01-01

Animal models which allow the temporal regulation of gene activities are valuable for dissecting gene function in tumorigenesis. Here we have constructed a conditional inducible estrogen receptor-K-ras(G12D) (ER-K-ras(G12D)) knock-in mice allele that allows us to temporally switch on or off the activity of K-ras oncogenic mutant through tamoxifen administration. In vitro studies using mice embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 µM works optimally for activation of ER-K-ras(G12D) independent of the gender status. Furthermore, tamoxifen-inducible activation of K-ras(G12D) promotes cell proliferation, anchor-independent growth, transformation as well as invasion, potentially via activation of downstream MAPK pathway and cell cycle progression. Continuous activation of K-ras(G12D) in vivo by tamoxifen treatment is sufficient to drive the neoplastic transformation of normal lung epithelial cells in mice. Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor regression in mouse lungs. Taken together, these data have convincingly demonstrated that K-ras mutant is essential for neoplastic transformation and this animal model may provide an ideal platform for further detailed characterization of the role of K-ras oncogenic mutant during different stages of lung tumorigenesis.

Ras mutation cooperates with β-catenin activation to drive bladder tumourigenesis.

PubMed

Ahmad, I; Patel, R; Liu, Y; Singh, L B; Taketo, M M; Wu, X-R; Leung, H Y; Sansom, O J

2011-03-03

Mutations in the Ras family of proteins (predominantly in H-Ras) occur in approximately 40% of urothelial cell carcinoma (UCC). However, relatively little is known about subsequent mutations/pathway alterations that allow tumour progression. Indeed, expressing mutant H-Ras within the mouse bladder does not lead to tumour formation, unless this is expressed at high levels. The Wnt signalling pathway is deregulated in approximately 25% of UCC, so we examined if this correlated with the activation of MAPK signalling in human UCC and found a significant correlation. To test the functional significance of this association we examined the impact of combining Ras mutation (H-Ras(Q61L) or K-Ras(G12D)) with an activating β-catenin mutation within the mouse bladder using Cre-LoxP technology. Although alone, neither Ras mutation nor β-catenin activation led to UCC (within 12 months), mice carrying both mutations rapidly developed UCC. Mechanistically this was associated with reduced levels of p21 with dependence on the MAPK signalling pathway. Moreover, tumours from these mice were sensitive to MEK inhibition. Importantly, in human UCC there was a negative correlation between levels of p-ERK and p21 suggesting that p21 accumulation may block tumour progression following Ras mutation. Taken together these data definitively show Ras pathway activation strongly cooperates with Wnt signalling to drive UCC in vivo.

Ras-GTP dimers activate the mitogen-activated protein kinase (MAPK) pathway

DOE PAGES

Nan, Xiaolin; Tamgüney, Tanja M.; Collisson, Eric A.; ...

2015-06-16

Rat sarcoma (Ras) GTPases regulate cell proliferation and survival through effector pathways including Raf-MAPK, and are the most frequently mutated genes in human cancer. Although it is well established that Ras activity requires binding to both GTP and the membrane, details of how Ras operates on the cell membrane to activate its effectors remain elusive. Efforts to target mutant Ras in human cancers to therapeutic benefit have also been largely unsuccessful. Here we show that Ras-GTP forms dimers to activate MAPK. We used quantitative photoactivated localization microscopy (PALM) to analyze the nanoscale spatial organization of PAmCherry1-tagged KRas 4B (hereafter referredmore » to KRas) on the cell membrane under various signaling conditions. We found that at endogenous expression levels KRas forms dimers, and KRas G12D, a mutant that constitutively binds GTP, activates MAPK. Overexpression of KRas leads to formation of higher order Ras nanoclusters. Conversely, at lower expression levels, KRas G12D is monomeric and activates MAPK only when artificially dimerized. Moreover, dimerization and signaling of KRas are both dependent on an intact CAAX (C, cysteine; A, aliphatic; X, any amino acid) motif that is also known to mediate membrane localization. These results reveal a new, dimerization-dependent signaling mechanism of Ras, and suggest Ras dimers as a potential therapeutic target in mutant Ras-driven tumors.« less

Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway

PubMed Central

Nan, Xiaolin; Tamgüney, Tanja M.; Collisson, Eric A.; Lin, Li-Jung; Pitt, Cameron; Galeas, Jacqueline; Lewis, Sophia; Gray, Joe W.; McCormick, Frank; Chu, Steven

2015-01-01

Rat sarcoma (Ras) GTPases regulate cell proliferation and survival through effector pathways including Raf-MAPK, and are the most frequently mutated genes in human cancer. Although it is well established that Ras activity requires binding to both GTP and the membrane, details of how Ras operates on the cell membrane to activate its effectors remain elusive. Efforts to target mutant Ras in human cancers to therapeutic benefit have also been largely unsuccessful. Here we show that Ras-GTP forms dimers to activate MAPK. We used quantitative photoactivated localization microscopy (PALM) to analyze the nanoscale spatial organization of PAmCherry1-tagged KRas 4B (hereafter referred to KRas) on the cell membrane under various signaling conditions. We found that at endogenous expression levels KRas forms dimers, and KRasG12D, a mutant that constitutively binds GTP, activates MAPK. Overexpression of KRas leads to formation of higher order Ras nanoclusters. Conversely, at lower expression levels, KRasG12D is monomeric and activates MAPK only when artificially dimerized. Moreover, dimerization and signaling of KRas are both dependent on an intact CAAX (C, cysteine; A, aliphatic; X, any amino acid) motif that is also known to mediate membrane localization. These results reveal a new, dimerization-dependent signaling mechanism of Ras, and suggest Ras dimers as a potential therapeutic target in mutant Ras-driven tumors. PMID:26080442

Reptile-associated salmonellosis in children aged under 5 years in South West England.

PubMed

Murphy, Dan; Oshin, Femi

2015-04-01

To determine the proportion of Salmonella cases in children aged <5 years that were reptile-associated salmonellosis (RAS) and to compare the severity of illness. To analyse all cases of salmonellosis reported to public health authorities in children aged under 5 years in the South West of the UK from January 2010 to December 2013 for reptile exposure, age, serotype, hospitalisation and invasive disease. 48 of 175 (27%) Salmonella cases had exposure to reptiles. The median age of RAS cases was significantly lower than non-RAS cases (0.5 vs 1.0 year). RAS cases were 2.5 times more likely to be hospitalised (23/48) compared with non-RAS cases (25/127; p=0.0002). This trend continued in cases aged under 12 months, with significantly more RAS cases hospitalised (19/38) than non-RAS cases (8/42; p=0.003). Significantly more RAS cases had invasive disease (8/48: 5 bacteraemia, 2 meningitis, 1 colitis) than non-RAS cases (4/127: 3 bacteraemia, 1 meningitis). Reptile exposure was found in over a quarter of all reported Salmonella cases in children under 5 years of age. RAS is associated with young age, hospitalisation and invasive disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The RasGAP Gene, RASAL2, is a Tumor and Metastasis Suppressor

PubMed Central

McLaughlin, Sara Koenig; Olsen, Sarah Naomi; Dake, Benjamin; De Raedt, Thomas; Lim, Elgene; Bronson, Roderick Terry; Beroukhim, Rameen; Polyak, Kornelia; Brown, Myles; Kuperwasser, Charlotte; Cichowski, Karen

2013-01-01

SUMMARY RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite the fact that Ras and ERK are frequently hyperactivated. Here we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer and RASAL2 ablation promotes tumor growth, progression, and metastasis in mouse models. In human breast cancer RASAL2-loss is associated with metastatic disease, low RASAL2 levels correlate with recurrence of luminal B tumors, and RASAL2 ablation promotes metastasis of luminal mouse tumors. Additional data reveal a broader role for RASAL2 inactivation in other tumor-types. These studies highlight the expanding role of RasGAPs and reveal an alternative mechanism of activating Ras in cancer. PMID:24029233

Nutrient digestibility response to sugarcane bagasse addition and corn particle size in normal and high Na diets for broilers.

PubMed

Kheravii, S K; Swick, R A; Choct, M; Wu, S-B

2018-04-01

Improving diet digestibility is important to the broiler industry. Therefore, this study focused on optimizing the physical structure of feed ingredients and addition of dietary fiber as strategies to improve nutrient digestibility in low and high sodium diets. A total of 672 day-old Ross 308 male broilers was allocated to 48 pens using a 2 × 2 × 2 factorial arrangement of treatments with 2 particle sizes of corn (coarse 3,576 μm or fine 1,113 μm geometric mean diameter), 2 levels of sugarcane bagasse (SB) (0 or 2%), and 2 levels of Na (0.16 or 0.4%). Protein digestibility coefficient was measured using pooled distal ileal digesta of 3 birds per pen on d 24. Meanwhile, starch and gross energy digestibility coefficients were measured using pooled duodenal, distal jejunal, and distal ileal digesta of 3 birds per pen on d 24. Coarsely ground corn (CC) resulted in improved ileal protein digestibility (P < 0.05). Addition of 2% SB increased starch digestibility in the duodenum (P < 0.05), distal jejunum (P < 0.001), and distal ileum (P < 0.001), and increased protein digestibility in distal ileum (P < 0.01). A significant particle size × SB × Na interaction was observed for ileal energy digestibility (P < 0.05). The SB increased ileal energy digestibility only in birds fed the diet with finely ground corn (FC) and 0.16% Na. These findings demonstrate that SB and CC are able to improve nutrient digestibility. It can be recommended for the poultry industry to use SB and coarsely ground corn in feed to improve the utilization of nutrients.

Larval fish feeding ecology, growth and mortality from two basins with contrasting environmental conditions of an inner sea of northern Patagonia, Chile.

PubMed

Landaeta, Mauricio F; Bustos, Claudia A; Contreras, Jorge E; Salas-Berríos, Franco; Palacios-Fuentes, Pámela; Alvarado-Niño, Mónica; Letelier, Jaime; Balbontín, Fernando

2015-05-01

During austral spring 2011, a survey was carried out in the inland sea (41°30'-44°S) of north Patagonia, South Pacific, studying a northern basin (NB: Reloncaví Fjord, Reloncaví Sound and Ancud Gulf) characterized by estuarine regime with stronger vertical stratification and warmer (11-14 °C) and most productive waters, and a southern basin (SB: Corcovado Gulf and Guafo mouth), with more oceanic water influence, showed mixed conditions of the water column, colder (11-10.5 °C) and less productive waters. Otolith microstructure and gut content analysis of larval lightfish Maurolicus parvipinnis and rockfish Sebastes oculatus were studied. Larval M. parvipinnis showed similar growth rates in both regions (0.13-0.15 mm d(-1)), but in NB larvae were larger-at-age than in SB. Larval S. oculatus showed no differences in size-at-age and larval growth (0.16 and 0.11 mm d(-1) for NB and SB, respectively). M. parvipinnis larvae from NB had larger number of prey items (mostly invertebrate eggs), similar total volume in their guts and smaller prey size than larvae collected in SB (mainly calanoid copepods). Larval S. oculatus had similar number, volume and body width of prey ingested at both basins, although prey ingestion rate by size was 5 times larger in NB than in SB, and prey composition varied from nauplii in NB to copepodites in SB. This study provides evidence that physical-biological interactions during larval stages of marine fishes from Chilean Patagonia are species-specific, and that in some cases large size-at-age correspond to increasing foraging success. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel strategy of nitrogen removal from domestic wastewater using pilot Orbal oxidation ditch.

PubMed

Gao, Shou-you; Peng, Yong-zhen; Wang, Shu-ying; Yan, Jun

2006-01-01

A pilot-scale Orbal oxidation ditch was operated for 17 months to optimize nitrogen removal from domestic wastewater of average COD to total nitrogen ratio of 2.7, with particular concern about the roles of dissolved oxygen (DO), mixed liquor suspended solids (MLSS) and return activated sludge (RAS) recycle ratio. Remarkable simultaneous nitrification and denitrification (SND) was observed and mean total nitrogen (TN) removal efficiency up to 72.1% was steadily achieved, at DO concentration in the out, middle and inner channel of 0.1, 0.4 and 0.7 mg/L, respectively, with an average MLSS of 5.5 g/L and RAS recycle ratio of 150%. Although the out channel took the major role in TN removal, the role of middle channel should never be ignored. The denitrification potential could be fully developed under low DO, high MLSS with adequate RAS ratio. The sludge settleability was amazingly improved under low DO operation mode, and some explanations were tried. In addition, a series of simplified batch tests were done to determine whether novel microorganisms could make substantial contribution to the performance of nitrogen removal. The results indicated that the SND observed in this Orbal oxidation ditch was more likely a physical phenomenon.

Quantitative two-dimensional gel electrophoresis analysis of human fibroblasts transformed by ras oncogenes.

PubMed

Miller, M J; Maher, V M; McCormick, J J

1992-11-01

Quantitative two-dimensional gel electrophoresis was used to compare the cellular protein patterns of a normal foreskin-derived human fibroblasts cell line (LG1) and three immortal derivatives of LG1. One derivative, designated MSU-1.1 VO, was selected for its ability to grow in the absence of serum and is non-tumorigenic in athymic mice. The other two strains were selected for focus-formation following transfection with either Ha-ras or N-ras oncogenes and form high grade malignant tumors. Correspondence and cluster analysis provided a nonbiased estimate of the relative similarity of the different two-dimensional patterns. These techniques separated the gel patterns into three distinct classes: LG1, MSU-1.1 VO, and the ras transformed cell strains. The MSU-1.1 VO cells were more closely related to the parental LG1 than to the ras-transformed cells. The differences between the three classes were primarily quantitative in nature: 16% of the spots demonstrated statistically significant changes (P < 0.01, T test, mean ratio of intensity > 2) in the rate of incorporation of radioactive amino acids. The patterns from the two ras-transformed cell strains were similar, and variations in the expression of proteins that occurred between the separate experiments obscured consistent differences between the Ha-ras and N-ras transformed cells. However, while only 9 out of 758 spots were classified as different (1%), correspondence analysis could consistently separate the two ras transformants. One of these spots was five times more intense in the Ha-ras transformed cells than the N-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for invasive reptile-associated salmonellosis in children.

PubMed

Meyer Sauteur, Patrick M; Relly, Christa; Hug, Martina; Wittenbrink, Max M; Berger, Christoph

2013-06-01

Reptile-associated salmonellosis (RAS) in children has been reported primarily due to direct contact with turtles, but recently also due to indirect contact with more exotic reptiles, causing disease in infants. To evaluate risk factors for RAS, we reviewed the RAS cases published in the literature since 1965. A case was defined as a child ≤18 years of age with an epidemiological link by identification of Salmonella enterica in cultures from both the affected child and the exposed reptile. We identified a total of 177 otherwise healthy children (median age 1.0 years, range 2 days to 17.0 years). RAS manifested mainly with gastrointestinal disease, but 15% presented with invasive RAS, including septicemia, meningitis, and bone and joint infection. The children with invasive RAS were significantly younger than children with noninvasive disease (median age 0.17 and 2.0 years, p<0.0001). RAS is most frequently seen after exposure to turtles (42%). However, children with invasive RAS had been exposed more often (p≤0.001) to reptiles other than turtles, including iguanas, bearded dragons, snakes, chameleons, and geckos. Children exposed to those latter reptiles usually kept indoors were younger than children exposed to turtles mostly kept outdoors (p<0.0001). RAS in children is significantly associated with invasive disease at young age, in particular infants <6 months of age. Exposure to reptiles, other than turtles, kept indoors is associated with RAS at younger age and more invasive disease. This finding is helpful for recognizing or even preventing invasive RAS in young infants that are at highest risk.

Mixing and compaction recommendations for warm mix asphalt (WMA) with recycled asphalt shingles (RAS) : final report.

DOT National Transportation Integrated Search

2017-05-01

The use of recycled asphalt shingles (RAS) is an attractive option for asphalt mixture producers due to the : high amount of recycled asphalt binder available in RAS. By weight, RAS contains 10 to 25% asphalt by total : weight of the shingle. The asp...

Tuning topological phases in the XMnSb2 system via chemical substitution from first principles

NASA Astrophysics Data System (ADS)

Griffin, Sinead M.; Neaton, Jeffrey B.

New Dirac materials are sought for their interesting fundamental physics and for their potential technological applications. Protected symmetries offer a route to potential zero mass Dirac and Weyl fermions, and can lead unique transport properties and spectroscopic signatures. In this work, we use first-principles calculations to study the XMnSb2 family of materials and show how varying X changes the nature of bulk protected topological features in their electronic structure. We further discuss new design rules for predicting new topological materials suggested by our calculations. SG is supported by the Early Postdoc Mobility Fellowship of the SNF.

Osteoporosis in paediatric patients with spina bifida.

PubMed

Marreiros, Humberto; Marreiros, Humberto Filipe; Loff, Clara; Calado, Eulalia

2012-01-01

The prevalence and morbidity associated with osteoporosis and fractures in patients with spina bifida (SB) highlight the importance of osteoporosis prevention and treatment in early childhood; however, the issue has received little attention. The method for the selection of appropriate patients for drug treatment has not been clarified. To review the literature concerning fracture risks and low bone density in paediatric patients with SB. We looked for studies describing state-of-the-art treatments and for prevention of secondary osteoporosis. Articles were identified through a search in the electronic database (PUBMED) supplemented with reviews of the reference lists of selected papers. The main outcome measures were incidence of fractures and risk factors for fracture, an association between bone mineral density (BMD) and occurrence of fracture, risk factors of low BMD, and effects of pharmacological and non-pharmacological treatments on BMD and on the incidence of fractures. We considered as a secondary outcome the occurrence of fractures in relation to the mechanism of injury. Results indicated that patients with SB are at increased risk for fractures and low BMD. Risk factors that may predispose patients to fractures include higher levels of neurological involvement, non-ambulatory status, physical inactivity, hypercalciuria, higher body fat levels, contractures, and a previous spontaneous fracture. Limitations were observed in the number and quality of studies concerning osteoporosis prevention and treatment in paediatric patients with SB. The safety and efficiency of drugs to treat osteoporosis in adults have not been evaluated satisfactorily in children with SB.

Regulating the Regulator: Post-Translational Modification of Ras

PubMed Central

Ahearn, Ian M.; Haigis, Kevin; Bar-Sagi, Dafna; Philips, Mark R.

2013-01-01

Ras proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on Ras is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which regulate the activation state of Ras without covalently modifying it. In contrast, post-translational modifications (PTMs) of Ras proteins direct them to various cellular membranes and, in some cases, modulate GTP–GDP exchange. Important Ras PTMs include the constitutive and irreversible remodelling of its C-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications including phosphorylation, peptidyl-proly isomerisation, mono- and di-ubiquitination, nitrosylation, ADP ribosylation and glucosylation. PMID:22189424

Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity.

PubMed

Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

2014-12-01

Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics and lipidomics was employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into four groups for 10 weeks: ad-libitum-fed sedentary control, ad-libitum-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE) and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67 and 110 genes were significantly changed in DCR, PE and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including up-regulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears that the reduction of both Ras-MAPK and PI3K-Akt signaling pathways is a cancer preventive target that has been consistently demonstrated by three bioinformatics approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.

PubMed

Schulz, Manon D; Atay, Ciğdem; Heringer, Jessica; Romrig, Franziska K; Schwitalla, Sarah; Aydin, Begüm; Ziegler, Paul K; Varga, Julia; Reindl, Wolfgang; Pommerenke, Claudia; Salinas-Riester, Gabriela; Böck, Andreas; Alpert, Carl; Blaut, Michael; Polson, Sara C; Brandl, Lydia; Kirchner, Thomas; Greten, Florian R; Polson, Shawn W; Arkan, Melek C

2014-10-23

Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known risk factors for gastrointestinal cancers. There is substantial evidence suggesting that diet markedly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development. However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-ras(G12Dint), mice independently of obesity. HFD consumption, in conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed K-ras(G12Dint) mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal tumours to healthy adult K-ras(G12Dint) mice was sufficient to transmit disease in the absence of an HFD. Furthermore, treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest that tumorigenesis is transmissible among genetically predisposed individuals.

Reduced signaling of PI3K-Akt and RAS-MAPK pathways are the key targets for weight loss-induced cancer prevention by dietary calorie restriction and/or physical activity

PubMed Central

Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

2014-01-01

Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics, and lipidomics were employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into 4 groups for 10 weeks: ad lib-fed sedentary control, ad lib-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE), and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics, and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67, and 110 genes were significantly changed in DCR, PE, and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including upregulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears the reduction of both Ras-MAPK and PI3K-Akt signaling pathways are cancer preventive targets that have been consistently demonstrated by three bioinformatics approaches. PMID:25283328

The possible mechanism of enhanced carcinogenesis induced by genotoxic carcinogens in rasH2 mice.

PubMed

Okamura, Miwa; Unami, Akira; Moto, Mitsuyoshi; Muguruma, Masako; Ito, Tadashi; Jin, Meilan; Oishi, Yuji; Kashida, Yoko; Mitsumori, Kunitoshi

2007-01-08

Microarray and RT-PCR analyses were performed for the transgene and Ras-related genes in forestomach squamous cell carcinomas (SCCs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rasH2 mice; these results were compared with our previous molecular data of N-ethyl-N-nitrosourea-induced forestomach SCCs and urethane-induced lung adenomas in rasH2 mice. Overexpression of the transgene was detected in the DMBA-induced SCCs, suggesting that the transgene plays an important role in enhanced carcinogenesis in rasH2 mice. In addition, the mouse endogenous ras genes were up-regulated in the DMBA-induced SCCs, and are probably involved in the tumorigenesis of forestomach SCCs. Genes such as osteopontin, Cks1b, Tpm1, Reck, gelsolin, and amphiregulin that were commonly altered in these three different carcinogen-induced tumors may contribute to the development of tumors in rasH2 mice.

Oncogenic Ras induces inflammatory cytokine production by up-regulating the squamous cell carcinoma antigens SerpinB3/B4

PubMed Central

Pan, Ji-An; Sun, Yu; Shi, Chanjuan; Li, Jinyu; Powers, R. Scott; Crawford, Howard C.; Zong, Wei-Xing

2014-01-01

Mounting evidence indicates that oncogenic Ras can modulate cell autonomous inflammatory cytokine production, although the underlying mechanism remains unclear. Here we show that squamous cell carcinoma antigens 1 and 2 (SCCA1/2), members of the Serpin family of serine/cysteine protease inhibitors, are transcriptionally up-regulated by oncogenic Ras via MAPK and the ETS family transcription factor PEA3. Increased SCCA expression leads to inhibition of protein turnover, unfolded protein response, activation of NF-κB, and is essential for Ras-mediated cytokine production and tumor growth. Analysis of human colorectal and pancreatic tumor samples reveals a positive correlation between Ras mutation, enhanced SCCA expression, and IL-6 expression. These results indicate that SCCA is a Ras-responsive factor that has a role in Ras-associated cytokine production and tumorigenesis. PMID:24759783

Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

PubMed

Murua Escobar, Hugo; Günther, Kathrin; Richter, Andreas; Soller, Jan T; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

2004-01-01

Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

EGFR and Ras regulate DDX59 during lung cancer development.

PubMed

Yang, Lin; Zhang, Hanyin; Chen, Dan; Ding, Peikun; Yuan, Yunchang; Zhang, Yandong

2018-02-05

Oncogenes EGFR and ras are frequently mutated and activated in human lung cancers. In this report, we found that both EGFR and Ras signaling can upregulate RNA helicase DDX59 in lung cancer cells. DDX59 can be induced through the mitogen activated protein kinase (MAPK) pathway after EGFR or Ras activation. Inhibitors for Ras/Raf/MAP pathway significantly decreased DDX59 expression at both protein and mRNA levels. Through immunohistochemistry, we found that DDX59 protein expression correlated with Ras and EGFR mutation status in human lung adenocarcinoma. Finally, through a xenograft nude mice model, we demonstrated that DDX59 is pivotal for EGFR mutated lung cancer cell growth in vivo. Our study identified a novel protein downstream of Ras and EGFR, which may serve as a potential therapeutic drug target for lung cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.