Recent Ultra High Energy neutrino bounds and multimessenger observations with the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Zas, Enrique

2018-01-01

The overall picture of the highest energy particles produced in the Universe is changing because of measurements made with the Pierre Auger Observatory. Composition studies of cosmic rays point towards an unexpected mixed composition of intermediate mass nuclei, more isotropic than anticipated, which is reshaping the future of the field and underlining the priority to understand composition at the highest energies. The Observatory is competitive in the search for neutrinos of all flavors above about 100 PeV by looking for very inclined showers produced deep in the atmosphere by neutrinos interacting either in the atmosphere or in the Earth's crust. It covers a large field of view between -85° and 60° declination in equatorial coordinates. Neutrinos are expected because of the existence of ultra high energy cosmic rays. They provide valuable complementary information, their fluxes being sensitive to the primary cosmic ray masses and their directions reflecting the source positions. We report the results of the neutrino search providing competitive bounds to neutrino production and strong constraints to a number of production models including cosmogenic neutrinos due to ultra high energy protons. We also report on two recent contributions of the Observatory to multimessenger studies by searching for correlations of neutrinos both with cosmic rays and with gravitational waves. The correlations of the directions of the highest energy astrophysical neutrinos discovered with IceCube with the highest energy cosmic rays detected with the Auger Observatory and the Telescope Array revealed an excess that is not statistically significant and is being monitored. The targeted search for neutrinos correlated with the discovery of the gravitational wave events GW150914 and GW151226 with advanced LIGO has led to the first bounds on the energy emitted by black hole mergers in Ultra-High Energy Neutrinos.

Muon and Gamma Bundles tracing Up-going Tau Neutrino Astronomy

NASA Astrophysics Data System (ADS)

Fargion, D.; de Santis, M.; de Sanctis Lucentini, P. G.; Grossi, M.

2004-11-01

Up-going and Horizontal Tau Air-Showers, UpTaus and HorTaus, may trace Ultra High Energy Neutrino Tau Earth Skimming at the edge of the horizons. Their secondaries (μ± and γ bundles with e± pair flashes) might trace their nature over UHECR secondaries in horizontal showers. Indeed the atmosphere act as a perfect amplifier as well as a filter for showers: down-ward and horizontal μ bundles may still be originated by far Ultra High Energy Cosmic Rays skimming the terrestrial atmosphere but their rich gamma component will be exponentially suppressed. At large zenith angles after crossing a large slant depth (Xmax > 3 × 103 g cm-2) the number of μ± and secondary γ's (produced by the e± pair from μ decay in flight) is comparable. On the other hand, up-ward muon bundles from UpTaus and HorTaus may arise within a young shower with a larger gamma-muon ratio (˜ 102), leaving its characteristic imprint. We estimate the UpTaus and HorTaus rate from the Earth and we evaluate the consequent event rate of μ±, e± and γ bundles. We show that such events even for minimal GZK neutrino fluxes could be detected by scintillator arrays placed on mountains at 1 -5 km and pointing to the horizon. The required array areas are within tens-hundreds of square meters. An optimal structure is an array of crown-like twin detectors facing the horizons. We argue that such detectors will be able to detect both muonic bundles at a minimal average flux of 10-11 cm-2 s-1 sr-1 and electromagnetic particles (γ, e±) at 3 × 10-9 cm-2 s-1 sr-1, a few times each year, even for the minimal GZK ν flux.

Spheromaks and how plasmas may explain the ultra high energy cosmic ray mystery

NASA Astrophysics Data System (ADS)

Fowler, T. Kenneth; Li, Hui

2016-10-01

> eV or more, finally ejected as ultra high energy cosmic rays (UHECRs) long regarded as one of the mysteries of astrophysics. The acceleration is mainly due to the drift cyclotron loss cone kinetic instability known from plasma research. Experiments and simulations are suggested to verify the acceleration process.

Blazar 3C 66A: Another extragalactic source of ultra-high-energy gamma-ray photons

NASA Astrophysics Data System (ADS)

Neshpor, Yu. I.; Stepanyan, A. A.; Kalekin, O. P.; Fomin, V. P.; Chalenko, N. N.; Shitov, V. G.

1998-03-01

he observations of the object 3C 66A which were carried out with the GT-48 gamma-ray telescope at the Crimean Astrophysical Observatory in November-December 1996 revealed a flux of ultra-high-energy (>10^12 eV) gamma-ray photons from this blazar. According to preliminary estimates, the photon flux is (31) 10^11 photons cm^-2 s^-1. The blazar 3C 66A is the third extragalactic object from which a flux of ultra- high-energy gamma-ray photons was detected. Fluxes of gamma-ray photons were previously detected from the galaxies Mk 421 and Mk 501 at the Whipple observatory. This result provides further evidence that active processes proceed in blazars which are accompanied by the generation of cosmic rays responsible for the emission of gamma-ray photons.

Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density

DOE PAGES

Li, Guosheng; Lu, Xiaochuan; Kim, Jin Yong; ...

2016-02-11

Here we demonstrate for the first time that planar Na-NiCl 2 batteries can be operated at an intermediate temperature of 190°C with ultra-high energy density. A specific energy density of 350 Wh/kg, which is 3 times higher than that of conventional tubular Na-NiCl 2 batteries operated at 280°C, was obtained for planar Na-NiCl 2 batteries operated at 190°C over a long-term cell test (1000 cycles). The high energy density and superior cycle stability are attributed to the slower particle growth of the cathode materials (NaCl and Ni) at 190°C. The results reported in this work demonstrate that planar Na-NiCl 2more » batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.« less

The Galactic Magnetic Field and Ultra-High Energy Cosmic Rays

NASA Astrophysics Data System (ADS)

Urban, Federico R.

The Galactic Magnetic Field is a peeving and importune screen between Ultra-High Energy Cosmic Rays and us cosmologists, engaged in the combat to unveil their properties and origin, as it deviates their paths towards the Earth in unpredictable ways. I will, in this order: briefly review the available field models on the market; explain a little trick which allows one to obtain cosmic rays deflection variances without even knowing what the (random) GMF model is; and argue that there is a lack of anisotropy in the large scales cosmic rays signal, which the Galactic field can do nothing about.

Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density

NASA Astrophysics Data System (ADS)

Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y.; Meinhardt, Kerry D.; Chang, Hee Jung; Canfield, Nathan L.; Sprenkle, Vincent L.

2016-02-01

Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg-1, higher than that of conventional tubular sodium-nickel chloride batteries (280 °C), is obtained for planar sodium-nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.

Review of total cross sections and forward scattering parameters at ultra-high energies

NASA Astrophysics Data System (ADS)

Block, M. M.; White, A. R.

1991-10-01

We review the field of the elastic scattering of pp and (bar p)p at the ultra-high energies. The recent total cross section, sigma (sub tot), and rho-value results from the Fermilab Tevatron Collider experiments presented at the 4th 'Blois' Workshop on Elastic and Diffractive Scattering (Elba, Italy, in May, 1991), allow us a comprehensive overview of the field.

Tau Kung | NREL

Science.gov Websites

Tau Kung Photo of Feitau Kung Tau Kung Commercial Buildings Research Engineer Feitau.Kung@nrel.gov evaluating building system energy performance in commercial settings, such as office, healthcare, higher

Ultra high energy gamma rays, cosmic rays and neutrinos from accreting degenerate stars

NASA Technical Reports Server (NTRS)

Brecher, K.; Chanmugam, G.

1985-01-01

Super-Eddington accretion for a recently proposed unipolar induction model of cosmic ray acceleration in accreting binary star systems containing magnetic white dwarfs or neutron stars is considered. For sufficiently high accretion rates and low magnetic fields, the model can account for: (1) acceleration of cosmic ray nuclei up to energies of 10 to the 19th power eV; (2) production of more or less normal solar cosmic ray composition; (3) the bulk of cosmic rays observed with energies above 1 TeV, and probably even down to somewhat lower energies as well; and (4) possibly the observed antiproton cosmic ray flux. It can also account for the high ultra high energy (UHE) gamma ray flux observed from several accreting binary systems (including Cygnus X-3), while allowing the possibility of an even higher neutrino flux from these sources, with L sub nu/L sub gamma is approximately 100.

High-energy ultra-short pulse thin-disk lasers: new developments and applications

NASA Astrophysics Data System (ADS)

Michel, Knut; Klingebiel, Sandro; Schultze, Marcel; Tesseit, Catherine Y.; Bessing, Robert; Häfner, Matthias; Prinz, Stefan; Sutter, Dirk; Metzger, Thomas

2016-03-01

We report on the latest developments at TRUMPF Scientific Lasers in the field of ultra-short pulse lasers with highest output energies and powers. All systems are based on the mature and industrialized thin-disk technology of TRUMPF. Thin Yb:YAG disks provide a reliable and efficient solution for power and energy scaling to Joule- and kW-class picosecond laser systems. Due to its efficient one dimensional heat removal, the thin-disk exhibits low distortions and thermal lensing even when pumped under extremely high pump power densities of 10kW/cm². Currently TRUMPF Scientific Lasers develops regenerative amplifiers with highest average powers, optical parametric amplifiers and synchronization schemes. The first few-ps kHz multi-mJ thin-disk regenerative amplifier based on the TRUMPF thindisk technology was developed at the LMU Munich in 20081. Since the average power and energy have continuously been increased, reaching more than 300W (10kHz repetition rate) and 200mJ (1kHz repetition rate) at pulse durations below 2ps. First experiments have shown that the current thin-disk technology supports ultra-short pulse laser solutions >1kW of average power. Based on few-picosecond thin-disk regenerative amplifiers few-cycle optical parametric chirped pulse amplifiers (OPCPA) can be realized. These systems have proven to be the only method for scaling few-cycle pulses to the multi-mJ energy level. OPA based few-cycle systems will allow for many applications such as attosecond spectroscopy, THz spectroscopy and imaging, laser wake field acceleration, table-top few-fs accelerators and laser-driven coherent X-ray undulator sources. Furthermore, high-energy picosecond sources can directly be used for a variety of applications such as X-ray generation or in atmospheric research.

Ultra-high-energy cosmic rays from radio galaxies

NASA Astrophysics Data System (ADS)

Eichmann, B.; Rachen, J. P.; Merten, L.; van Vliet, A.; Becker Tjus, J.

2018-02-01

Radio galaxies are intensively discussed as the sources of cosmic rays observed above about 3 × 1018 eV, called ultra-high energy cosmic rays (UHECRs). We present a first, systematic approach that takes the individual characteristics of these sources into account, as well as the impact of the extragalactic magnetic-field structures up to a distance of 120 Mpc. We use a mixed simulation setup, based on 3D simulations of UHECRs ejected by observed, individual radio galaxies taken out to a distance of 120 Mpc, and on 1D simulations over a continuous source distribution contributing from beyond 120 Mpc. Additionally, we include the ultra-luminous radio galaxy Cygnus A at a distance of about 250 Mpc, as its contribution is so strong that it must be considered as an individual point source. The implementation of the UHECR ejection in our simulation setup, both that of individual radio galaxies and the continuous source function, is based on a detailed consideration of the physics of radio jets and standard first-order Fermi acceleration. This allows to derive the spectrum of ejected UHECR as a function of radio luminosity, and at the same time provides an absolute normalization of the problem involving only a small set of parameters adjustable within narrow constraints. We show that the average contribution of radio galaxies taken over a very large volume cannot explain the observed features of UHECRs measured at Earth. However, we obtain excellent agreement with the spectrum, composition, and arrival-direction distribution of UHECRs measured by the Pierre Auger Observatory, if we assume that most UHECRs observed arise from only two sources: the ultra-luminous radio galaxy Cygnus A, providing a mostly light composition of nuclear species dominating up to about 6 × 1019 eV, and the nearest radio galaxy Centaurus A, providing a heavy composition dominating above 6 × 1019 eV . Here we have to assume that extragalactic magnetic fields out to 250 Mpc, which we did not

Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density.

PubMed

Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y; Meinhardt, Kerry D; Chang, Hee Jung; Canfield, Nathan L; Sprenkle, Vincent L

2016-02-11

Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg(-1), higher than that of conventional tubular sodium-nickel chloride batteries (280 °C), is obtained for planar sodium-nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.

Advanced intermediate temperature sodium–nickel chloride batteries with ultra-high energy density

PubMed Central

Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y.; Meinhardt, Kerry D.; Chang, Hee Jung; Canfield, Nathan L.; Sprenkle, Vincent L.

2016-01-01

Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium–nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg−1, higher than that of conventional tubular sodium–nickel chloride batteries (280 °C), is obtained for planar sodium–nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium–nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs. PMID:26864635

Ultra-high energy cosmic rays from white dwarf pulsars and the Hillas criterion

NASA Astrophysics Data System (ADS)

Lobato, Ronaldo V.; Coelho, Jaziel G.; Malheiro, M.

2017-06-01

The origins of ultra-high-energy cosmic rays (E ≳ 1019 eV) are a mystery and still under debate in astroparticle physics. In recent years some efforts were made to understand their nature. In this contribution we consider the possibility of Some Soft Gamma Repeaters (SGRs) and Anomalous X-ray Pulsars (AXPs) beeing white dwarf pulsars, and show that these sources can achieve large electromagnetic potentials on their surface that accelerate particle almost at the speed of light, with energies E ~ 1020-21 eV. The sources SGRs/AXPs considered as highly magnetized white dwarfs are well described in the Hillas diagram, lying close to the AR Sorpii and AE Aquarii which are understood as white dwarf pulsars.

Simulations of ultra-high energy cosmic rays in the local Universe and the origin of cosmic magnetic fields

NASA Astrophysics Data System (ADS)

Hackstein, S.; Vazza, F.; Brüggen, M.; Sorce, J. G.; Gottlöber, S.

2018-04-01

We simulate the propagation of cosmic rays at ultra-high energies, ≳1018 eV, in models of extragalactic magnetic fields in constrained simulations of the local Universe. We use constrained initial conditions with the cosmological magnetohydrodynamics code ENZO. The resulting models of the distribution of magnetic fields in the local Universe are used in the CRPROPA code to simulate the propagation of ultra-high energy cosmic rays. We investigate the impact of six different magneto-genesis scenarios, both primordial and astrophysical, on the propagation of cosmic rays over cosmological distances. Moreover, we study the influence of different source distributions around the Milky Way. Our study shows that different scenarios of magneto-genesis do not have a large impact on the anisotropy measurements of ultra-high energy cosmic rays. However, at high energies above the Greisen-Zatsepin-Kuzmin (GZK)-limit, there is anisotropy caused by the distribution of nearby sources, independent of the magnetic field model. This provides a chance to identify cosmic ray sources with future full-sky measurements and high number statistics at the highest energies. Finally, we compare our results to the dipole signal measured by the Pierre Auger Observatory. All our source models and magnetic field models could reproduce the observed dipole amplitude with a pure iron injection composition. Our results indicate that the dipole is observed due to clustering of secondary nuclei in direction of nearby sources of heavy nuclei. A light injection composition is disfavoured, since the increase in dipole angular power from 4 to 8 EeV is too slow compared to observation by the Pierre Auger Observatory.

Fornax A, Centaurus A other radio galaxies as sources of ultra-high energy cosmic rays

NASA Astrophysics Data System (ADS)

Matthews, J. H.; Bell, A. R.; Blundell, K. M.; Araudo, A. T.

2018-06-01

The origin of ultra-high energy cosmic rays (UHECRs) is still unknown. It has recently been proposed that UHECR anisotropies can be attributed to starburst galaxies or active galactic nuclei. We suggest that the latter is more likely and that giant-lobed radio galaxies such as Centaurus A and Fornax A can explain the data.

Identification and energy calibration of hadronically decaying tau leptons with the ATLAS experiment in pp collisions at [Formula: see text][Formula: see text].

PubMed

Aad, G; Abbott, B; Abdallah, J; Abdel Khalek, S; Abdinov, O; Aben, R; Abi, B; Abolins, M; AbouZeid, O S; Abramowicz, H; Abreu, H; Abreu, R; Abulaiti, Y; Acharya, B S; Adamczyk, L; Adams, D L; Adelman, J; Adomeit, S; Adye, T; Agatonovic-Jovin, T; Aguilar-Saavedra, J A; Agustoni, M; Ahlen, S P; Ahmadov, F; Aielli, G; Akerstedt, H; Åkesson, T P A; Akimoto, G; Akimov, A V; Alberghi, G L; Albert, J; Albrand, S; Alconada Verzini, M J; Aleksa, M; Aleksandrov, I N; Alexa, C; Alexander, G; Alexandre, G; Alexopoulos, T; Alhroob, M; Alimonti, G; Alio, L; Alison, J; Allbrooke, B M M; Allison, L J; Allport, P P; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Altheimer, A; Alvarez Gonzalez, B; Alviggi, M G; Amako, K; Amaral Coutinho, Y; Amelung, C; Amidei, D; Amor Dos Santos, S P; Amorim, A; Amoroso, S; Amram, N; Amundsen, G; Anastopoulos, C; Ancu, L S; Andari, N; Andeen, T; Anders, C F; Anders, G; Anderson, K J; Andreazza, A; Andrei, V; Anduaga, X S; Angelidakis, S; Angelozzi, I; Anger, P; Angerami, A; Anghinolfi, F; Anisenkov, A V; Anjos, N; Annovi, A; Antonaki, A; Antonelli, M; Antonov, A; Antos, J; Anulli, F; Aoki, M; Aperio Bella, L; Apolle, R; Arabidze, G; Aracena, I; Arai, Y; Araque, J P; Arce, A T H; Arduh, F A; Arguin, J-F; Argyropoulos, S; Arik, M; Armbruster, A J; Arnaez, O; Arnal, V; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Asai, S; Asbah, N; Ashkenazi, A; Åsman, B; Asquith, L; Assamagan, K; Astalos, R; Atkinson, M; Atlay, N B; Auerbach, B; Augsten, K; Aurousseau, M; Avolio, G; Axen, B; Azuelos, G; Azuma, Y; Baak, M A; Baas, A E; Bacci, C; Bachacou, H; Bachas, K; Backes, M; Backhaus, M; Backus Mayes, J; Badescu, E; Bagiacchi, P; Bagnaia, P; Bai, Y; Bain, T; Baines, J T; Baker, O K; Balek, P; Balli, F; Banas, E; Banerjee, Sw; Bannoura, A A E; Bansil, H S; Barak, L; Baranov, S P; Barberio, E L; Barberis, D; Barbero, M; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnes, S L; Barnett, B M; Barnett, R M; Barnovska, Z; Baroncelli, A; Barone, G; Barr, A J; Barreiro, F; Barreiro Guimarães da Costa, J; Bartoldus, R; Barton, A E; Bartos, P; Bartsch, V; Bassalat, A; Basye, A; Bates, R L; Batista, S J; Batley, J R; Battaglia, M; Battistin, M; Bauer, F; Bawa, H S; Beattie, M D; Beau, T; Beauchemin, P H; Beccherle, R; Bechtle, P; Beck, H P; Becker, K; Becker, S; Beckingham, M; Becot, C; Beddall, A J; Bedikian, S; Beddall, A; Bednyakov, V A; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, K; Belanger-Champagne, C; Bell, P J; Bell, W H; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Benary, O; Benchekroun, D; Bendtz, K; Benekos, N; Benhammou, Y; Benhar Noccioli, E; Benitez Garcia, J A; Benjamin, D P; Bensinger, J R; Bentvelsen, S; Berge, D; Bergeaas Kuutmann, E; Berger, N; Berghaus, F; Beringer, J; Bernard, C; Bernat, P; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertsche, C; Bertsche, D; Besana, M I; Besjes, G J; Bessidskaia Bylund, O; Bessner, M; Besson, N; Betancourt, C; Bethke, S; Bhimji, W; Bianchi, R M; Bianchini, L; Bianco, M; Biebel, O; Bieniek, S P; Bierwagen, K; Biesiada, J; Biglietti, M; Bilbao De Mendizabal, J; Bilokon, H; Bindi, M; Binet, S; Bingul, A; Bini, C; Black, C W; Black, J E; Black, K M; Blackburn, D; Blair, R E; Blanchard, J-B; Blazek, T; Bloch, I; Blocker, C; Blum, W; Blumenschein, U; Bobbink, G J; Bobrovnikov, V S; Bocchetta, S S; Bocci, A; Bock, C; Boddy, C R; Boehler, M; Boek, T T; Bogaerts, J A; Bogdanchikov, A G; Bogouch, A; Bohm, C; Boisvert, V; Bold, T; Boldea, V; Boldyrev, A S; Bomben, M; Bona, M; Boonekamp, M; Borisov, A; Borissov, G; Borri, M; Borroni, S; Bortfeldt, J; Bortolotto, V; Bos, K; Boscherini, D; Bosman, M; Boterenbrood, H; Boudreau, J; Bouffard, J; Bouhova-Thacker, E V; Boumediene, D; Bourdarios, C; Bousson, N; Boutouil, S; Boveia, A; Boyd, J; Boyko, I R; Bozic, I; Bracinik, J; Brandt, A; Brandt, G; Brandt, O; Bratzler, U; Brau, B; Brau, J E; Braun, H M; Brazzale, S F; Brelier, B; Brendlinger, K; Brennan, A J; Brenner, R; Bressler, S; Bristow, K; Bristow, T M; Britton, D; Brochu, F M; Brock, I; Brock, R; Bronner, J; Brooijmans, G; Brooks, T; Brooks, W K; Brosamer, J; Brost, E; Brown, J; Bruckman de Renstrom, P A; Bruncko, D; Bruneliere, R; Brunet, S; Bruni, A; Bruni, G; Bruschi, M; Bryngemark, L; Buanes, T; Buat, Q; Bucci, F; Buchholz, P; Buckley, A G; Buda, S I; Budagov, I A; Buehrer, F; Bugge, L; Bugge, M K; Bulekov, O; Bundock, A C; Burckhart, H; Burdin, S; Burghgrave, B; Burke, S; Burmeister, I; Busato, E; Büscher, D; Büscher, V; Bussey, P; Buszello, C P; Butler, B; Butler, J M; Butt, A I; Buttar, C M; Butterworth, J M; Butti, P; Buttinger, W; Buzatu, A; Byszewski, M; Cabrera Urbán, S; Caforio, D; Cakir, O; Calafiura, P; Calandri, A; Calderini, G; Calfayan, P; Calkins, R; Caloba, L P; Calvet, D; Calvet, S; Camacho Toro, R; Camarda, S; Cameron, D; Caminada, L M; Caminal Armadans, R; Campana, S; Campanelli, M; Campoverde, A; Canale, V; Canepa, A; Cano Bret, M; Cantero, J; Cantrill, R; Cao, T; Capeans Garrido, M D M; Caprini, I; Caprini, M; Capua, M; Caputo, R; Cardarelli, R; Carli, T; Carlino, G; Carminati, L; Caron, S; Carquin, E; Carrillo-Montoya, G D; Carter, J R; Carvalho, J; Casadei, D; Casado, M P; Casolino, M; Castaneda-Miranda, E; Castelli, A; Castillo Gimenez, V; Castro, N F; Catastini, P; Catinaccio, A; Catmore, J R; Cattai, A; Cattani, G; Caudron, J; Cavaliere, V; Cavalli, D; Cavalli-Sforza, M; Cavasinni, V; Ceradini, F; Cerio, B C; Cerny, K; Cerqueira, A S; Cerri, A; Cerrito, L; Cerutti, F; Cerv, M; Cervelli, A; Cetin, S A; Chafaq, A; Chakraborty, D; Chalupkova, I; Chang, P; Chapleau, B; Chapman, J D; Charfeddine, D; Charlton, D G; Chau, C C; Chavez Barajas, C A; Cheatham, S; Chegwidden, A; Chekanov, S; Chekulaev, S V; Chelkov, G A; Chelstowska, M A; Chen, C; Chen, H; Chen, K; Chen, L; Chen, S; Chen, X; Chen, Y; Cheng, H C; Cheng, Y; Cheplakov, A; Cherkaoui El Moursli, R; Chernyatin, V; Cheu, E; Chevalier, L; Chiarella, V; Chiefari, G; Childers, J T; Chilingarov, A; Chiodini, G; Chisholm, A S; Chislett, R T; Chitan, A; Chizhov, M V; Chouridou, S; Chow, B K B; Chromek-Burckhart, D; Chu, M L; Chudoba, J; Chwastowski, J J; Chytka, L; Ciapetti, G; Ciftci, A K; Ciftci, R; Cinca, D; Cindro, V; Ciocio, A; Citron, Z H; Citterio, M; Ciubancan, M; Clark, A; Clark, P J; Clarke, R N; Cleland, W; Clemens, J C; Clement, C; Coadou, Y; Cobal, M; Coccaro, A; Cochran, J; Coffey, L; Cogan, J G; Cole, B; Cole, S; Colijn, A P; Collot, J; Colombo, T; Compostella, G; Conde Muiño, P; Coniavitis, E; Connell, S H; Connelly, I A; Consonni, S M; Consorti, V; Constantinescu, S; Conta, C; Conti, G; Conventi, F; Cooke, M; Cooper, B D; Cooper-Sarkar, A M; Cooper-Smith, N J; Copic, K; Cornelissen, T; Corradi, M; Corriveau, F; Corso-Radu, A; Cortes-Gonzalez, A; Cortiana, G; Costa, G; Costa, M J; Costanzo, D; Côté, D; Cottin, G; Cowan, G; Cox, B E; Cranmer, K; Cree, G; Crépé-Renaudin, S; Crescioli, F; Cribbs, W A; Crispin Ortuzar, M; Cristinziani, M; Croft, V; Crosetti, G; Cuhadar Donszelmann, T; Cummings, J; Curatolo, M; Cuthbert, C; Czirr, H; Czodrowski, P; D'Auria, S; D'Onofrio, M; Cunha Sargedas De Sousa, M J Da; Via, C Da; Dabrowski, W; Dafinca, A; Dai, T; Dale, O; Dallaire, F; Dallapiccola, C; Dam, M; Daniells, A C; Dano Hoffmann, M; Dao, V; Darbo, G; Darmora, S; Dassoulas, J; Dattagupta, A; Davey, W; David, C; Davidek, T; Davies, E; Davies, M; Davignon, O; Davison, A R; Davison, P; Davygora, Y; Dawe, E; Dawson, I; Daya-Ishmukhametova, R K; De, K; de Asmundis, R; De Castro, S; De Cecco, S; De Groot, N; de Jong, P; De la Torre, H; De Lorenzi, F; De Nooij, L; De Pedis, D; De Salvo, A; De Sanctis, U; De Santo, A; De Vivie De Regie, J B; Dearnaley, W J; Debbe, R; Debenedetti, C; Dechenaux, B; Dedovich, D V; Deigaard, I; Del Peso, J; Del Prete, T; Deliot, F; Delitzsch, C M; Deliyergiyev, M; Dell'Acqua, A; Dell'Asta, L; Dell'Orso, M; Della Pietra, M; Della Volpe, D; Delmastro, M; Delsart, P A; Deluca, C; DeMarco, D A; Demers, S; Demichev, M; Demilly, A; Denisov, S P; Derendarz, D; Derkaoui, J E; Derue, F; Dervan, P; Desch, K; Deterre, C; Deviveiros, P O; Dewhurst, A; Dhaliwal, S; Di Ciaccio, A; Di Ciaccio, L; Di Domenico, A; Di Donato, C; Di Girolamo, A; Di Girolamo, B; Di Mattia, A; Di Micco, B; Di Nardo, R; Di Simone, A; Di Sipio, R; Di Valentino, D; Dias, F A; Diaz, M A; Diehl, E B; Dietrich, J; Dietzsch, T A; Diglio, S; Dimitrievska, A; Dingfelder, J; Dita, P; Dita, S; Dittus, F; Djama, F; Djobava, T; Djuvsland, J I; do Vale, M A B; Dobos, D; Doglioni, C; Doherty, T; Dohmae, T; Dolejsi, J; Dolezal, Z; Dolgoshein, B A; Donadelli, M; Donati, S; Dondero, P; Donini, J; Dopke, J; Doria, A; Dova, M T; Doyle, A T; Dris, M; Dubbert, J; Dube, S; Dubreuil, E; Duchovni, E; Duckeck, G; Ducu, O A; Duda, D; Dudarev, A; Dudziak, F; Duflot, L; Duguid, L; Dührssen, M; Dunford, M; Duran Yildiz, H; Düren, M; Durglishvili, A; Duschinger, D; Dwuznik, M; Dyndal, M; Ebke, J; Edson, W; Edwards, N C; Ehrenfeld, W; Eifert, T; Eigen, G; Einsweiler, K; Ekelof, T; El Kacimi, M; Ellert, M; Elles, S; Ellinghaus, F; Ellis, N; Elmsheuser, J; Elsing, M; Emeliyanov, D; Enari, Y; Endner, O C; Endo, M; Engelmann, R; Erdmann, J; Ereditato, A; Eriksson, D; Ernis, G; Ernst, J; Ernst, M; Ernwein, J; Errede, D; Errede, S; Ertel, E; Escalier, M; Esch, H; Escobar, C; Esposito, B; Etienvre, A I; Etzion, E; Evans, H; Ezhilov, A; Fabbri, L; Facini, G; Fakhrutdinov, R M; Falciano, S; Falla, R J; Faltova, J; Fang, Y; Fanti, M; Farbin, A; Farilla, A; Farooque, T; Farrell, S; Farrington, S M; Farthouat, P; Fassi, F; Fassnacht, P; Fassouliotis, D; Favareto, A; Fayard, L; Federic, P; Fedin, O L; Fedorko, W; Feigl, S; Feligioni, L; Feng, C; Feng, E J; Feng, H; Fenyuk, A B; Fernandez Perez, S; Ferrag, S; Ferrando, J; Ferrari, A; Ferrari, P; Ferrari, R; Ferreira de Lima, D E; Ferrer, A; Ferrere, D; Ferretti, C; Ferretto Parodi, A; Fiascaris, M; Fiedler, F; Filipčič, A; Filipuzzi, M; Filthaut, F; Fincke-Keeler, M; Finelli, K D; Fiolhais, M C N; Fiorini, L; Firan, A; Fischer, A; Fischer, J; Fisher, W C; Fitzgerald, E A; Flechl, M; Fleck, I; Fleischmann, P; Fleischmann, S; Fletcher, G T; Fletcher, G; Flick, T; Floderus, A; Flores Castillo, L R; Flowerdew, M J; Formica, A; Forti, A; Fortin, D; Fournier, D; Fox, H; Fracchia, S; Francavilla, P; Franchini, M; Franchino, S; Francis, D; Franconi, L; Franklin, M; Fraternali, M; French, S T; Friedrich, C; Friedrich, F; Froidevaux, D; Frost, J A; Fukunaga, C; Fullana Torregrosa, E; Fulsom, B G; Fuster, J; Gabaldon, C; Gabizon, O; Gabrielli, A; Gabrielli, A; Gadatsch, S; Gadomski, S; Gagliardi, G; Gagnon, P; Galea, C; Galhardo, B; Gallas, E J; Gallop, B J; Gallus, P; Galster, G; Gan, K K; Gao, J; Gao, Y S; Garay Walls, F M; Garberson, F; García, C; García Navarro, J E; Garcia-Sciveres, M; Gardner, R W; Garelli, N; Garonne, V; Gatti, C; Gaudio, G; Gaur, B; Gauthier, L; Gauzzi, P; Gavrilenko, I L; Gay, C; Gaycken, G; Gazis, E N; Ge, P; Gecse, Z; Gee, C N P; Geerts, D A A; Geich-Gimbel, Ch; Gellerstedt, K; Gemme, C; Gemmell, A; Genest, M H; Gentile, S; George, M; George, S; Gerbaudo, D; Gershon, A; Ghazlane, H; Ghodbane, N; Giacobbe, B; Giagu, S; Giangiobbe, V; Giannetti, P; Gianotti, F; Gibbard, B; Gibson, S M; Gilchriese, M; Gillam, T P S; Gillberg, D; Gilles, G; Gingrich, D M; Giokaris, N; Giordani, M P; Giordano, R; Giorgi, F M; Giorgi, F M; Giraud, P F; Giugni, D; Giuliani, C; Giulini, M; Gjelsten, B K; Gkaitatzis, S; Gkialas, I; Gkougkousis, E L; Gladilin, L K; Glasman, C; Glatzer, J; Glaysher, P C F; Glazov, A; Glonti, G L; Glonti, G L; Goblirsch-Kolb, M; Goddard, J R; Godlewski, J; Goeringer, C; Goldfarb, S; Golling, T; Golubkov, D; Gomes, A; Gomez Fajardo, L S; Gonçalo, R; Goncalves Pinto Firmino Da Costa, J; Gonella, L; González de la Hoz, S; Gonzalez Parra, G; Gonzalez-Sevilla, S; Goossens, L; Gorbounov, P A; Gordon, H A; Gorelov, I; Gorini, B; Gorini, E; Gorišek, A; Gornicki, E; Goshaw, A T; Gössling, C; Gostkin, M I; Gouighri, M; Goujdami, D; Goulette, M P; Goussiou, A G; Goy, C; Grabas, H M X; Graber, L; Grabowska-Bold, I; Grafström, P; Grahn, K-J; Gramling, J; Gramstad, E; Grancagnolo, S; Grassi, V; Gratchev, V; Gray, H M; Graziani, E; Grebenyuk, O G; Greenwood, Z D; Gregersen, K; Gregor, I M; Grenier, P; Griffiths, J; Grillo, A A; Grimm, K; Grinstein, S; Gris, Ph; Grishkevich, Y V; Grivaz, J-F; Grohs, J P; Grohsjean, A; Gross, E; Grosse-Knetter, J; Grossi, G C; Grout, Z J; Guan, L; Guenther, J; Guescini, F; Guest, D; Gueta, O; Guicheney, C; Guido, E; Guillemin, T; Guindon, S; Gul, U; Gumpert, C; Guo, J; Gupta, S; Gutierrez, P; Gutierrez Ortiz, N G; Gutschow, C; Guttman, N; Guyot, C; Gwenlan, C; Gwilliam, C B; Haas, A; Haber, C; Hadavand, H K; Haddad, N; Haefner, P; Hageböck, S; Hajduk, Z; Hakobyan, H; Haleem, M; Hall, D; Halladjian, G; Hallewell, G D; Hamacher, K; Hamal, P; Hamano, K; Hamer, M; Hamilton, A; Hamilton, S; Hamity, G N; Hamnett, P G; Han, L; Hanagaki, K; Hanawa, K; Hance, M; Hanke, P; Hanna, R; Hansen, J B; Hansen, J D; Hansen, P H; Hara, K; Hard, A S; Harenberg, T; Hariri, F; Harkusha, S; Harper, D; Harrington, R D; Harris, O M; Harrison, P F; Hartjes, F; Hasegawa, M; Hasegawa, S; Hasegawa, Y; Hasib, A; Hassani, S; Haug, S; Hauschild, M; Hauser, R; Havranek, M; Hawkes, C M; Hawkings, R J; Hawkins, A D; Hayashi, T; Hayden, D; Hays, C P; Hays, J M; Hayward, H S; Haywood, S J; Head, S J; Heck, T; Hedberg, V; Heelan, L; Heim, S; Heim, T; Heinemann, B; Heinrich, L; Hejbal, J; Helary, L; Heller, C; Heller, M; Hellman, S; Hellmich, D; Helsens, C; Henderson, J; Henderson, R C W; Heng, Y; Hengler, C; Henrichs, A; Henriques Correia, A M; Henrot-Versille, S; Herbert, G H; Hernández Jiménez, Y; Herrberg-Schubert, R; Herten, G; Hertenberger, R; Hervas, L; Hesketh, G G; Hessey, N P; Hickling, R; Higón-Rodriguez, E; Hill, E; Hill, J C; Hiller, K H; Hillier, S J; Hinchliffe, I; Hines, E; Hirose, M; Hirschbuehl, D; Hobbs, J; Hod, N; Hodgkinson, M C; Hodgson, P; Hoecker, A; Hoeferkamp, M R; Hoenig, F; Hoffmann, D; Hohlfeld, M; Holmes, T R; Hong, T M; Hooft van Huysduynen, L; Hopkins, W H; Horii, Y; Horton, A J; Hostachy, J-Y; Hou, S; Hoummada, A; Howard, J; Howarth, J; Hrabovsky, M; Hristova, I; Hrivnac, J; Hryn'ova, T; Hrynevich, A; Hsu, C; Hsu, P J; Hsu, S-C; Hu, D; Hu, X; Huang, Y; Hubacek, Z; Hubaut, F; Huegging, F; Huffman, T B; Hughes, E W; Hughes, G; Huhtinen, M; Hülsing, T A; Hurwitz, M; Huseynov, N; Huston, J; Huth, J; Iacobucci, G; Iakovidis, G; Ibragimov, I; Iconomidou-Fayard, L; Ideal, E; Idrissi, Z; Iengo, P; Igonkina, O; Iizawa, T; Ikegami, Y; Ikematsu, K; Ikeno, M; Ilchenko, Y; Iliadis, D; Ilic, N; Inamaru, Y; Ince, T; Ioannou, P; Iodice, M; Iordanidou, K; Ippolito, V; Irles Quiles, A; Isaksson, C; Ishino, M; Ishitsuka, M; Ishmukhametov, R; Issever, C; Istin, S; Iturbe Ponce, J M; Iuppa, R; Ivarsson, J; Iwanski, W; Iwasaki, H; Izen, J M; Izzo, V; Jackson, B; Jackson, M; Jackson, P; Jaekel, M R; Jain, V; Jakobs, K; Jakobsen, S; Jakoubek, T; Jakubek, J; Jamin, D O; Jana, D K; Jansen, E; Jansen, H; Janssen, J; Janus, M; Jarlskog, G; Javadov, N; Javůrek, T; Jeanty, L; Jejelava, J; Jeng, G-Y; Jennens, D; Jenni, P; Jentzsch, J; Jeske, C; Jézéquel, S; Ji, H; Jia, J; Jiang, Y; Jimenez Belenguer, M; Jin, S; Jinaru, A; Jinnouchi, O; Joergensen, M D; Johansson, K E; Johansson, P; Johns, K A; Jon-And, K; Jones, G; Jones, R W L; Jones, T J; Jongmanns, J; Jorge, P M; Joshi, K D; Jovicevic, J; Ju, X; Jung, C A; Jungst, R M; Jussel, P; Juste Rozas, A; Kaci, M; Kaczmarska, A; Kado, M; Kagan, H; Kagan, M; Kajomovitz, E; Kalderon, C W; Kama, S; Kamenshchikov, A; Kanaya, N; Kaneda, M; Kaneti, S; Kantserov, V A; Kanzaki, J; Kaplan, B; Kapliy, A; Kar, D; Karakostas, K; Karastathis, N; Kareem, M J; Karnevskiy, M; Karpov, S N; Karpova, Z M; Karthik, K; Kartvelishvili, V; Karyukhin, A N; Kashif, L; Kasieczka, G; Kass, R D; Kastanas, A; Kataoka, Y; Katre, A; Katzy, J; Kaushik, V; Kawagoe, K; Kawamoto, T; Kawamura, G; Kazama, S; Kazanin, V F; Kazarinov, M Y; Keeler, R; Kehoe, R; Keil, M; Keller, J S; Kempster, J J; Keoshkerian, H; Kepka, O; Kerševan, B P; Kersten, S; Kessoku, K; Keung, J; Keyes, R A; Khalil-Zada, F; Khandanyan, H; Khanov, A; Kharlamov, A; Khodinov, A; Khomich, A; Khoo, T J; Khoriauli, G; Khovanskiy, V; Khramov, E; Khubua, J; Kim, H Y; Kim, H; Kim, S H; Kimura, N; Kind, O; King, B T; King, M; King, R S B; King, S B; Kirk, J; Kiryunin, A E; Kishimoto, T; Kisielewska, D; Kiss, F; Kiuchi, K; Kladiva, E; Klein, M; Klein, U; Kleinknecht, K; Klimek, P; Klimentov, A; Klingenberg, R; Klinger, J A; Klioutchnikova, T; Klok, P F; Kluge, E-E; Kluit, P; Kluth, S; Kneringer, E; Knoops, E B F G; Knue, A; Kobayashi, D; Kobayashi, T; Kobel, M; Kocian, M; Kodys, P; Koffas, T; Koffeman, E; Kogan, L A; Kohlmann, S; Kohout, Z; Kohriki, T; Koi, T; Kolanoski, H; Koletsou, I; Koll, J; Komar, A A; Komori, Y; Kondo, T; Kondrashova, N; Köneke, K; König, A C; König, S; Kono, T; Konoplich, R; Konstantinidis, N; Kopeliansky, R; Koperny, S; Köpke, L; Kopp, A K; Korcyl, K; Kordas, K; Korn, A; Korol, A A; Korolkov, I; Korolkova, E V; Korotkov, V A; Kortner, O; Kortner, S; Kostyukhin, V V; Kotov, V M; Kotwal, A; Kourkoumeli-Charalampidi, A; Kourkoumelis, C; Kouskoura, V; Koutsman, A; Kowalewski, R; Kowalski, T Z; Kozanecki, W; Kozhin, A S; Kramarenko, V A; Kramberger, G; Krasnopevtsev, D; Krasny, M W; Krasznahorkay, A; Kraus, J K; Kravchenko, A; Kreiss, S; Kretz, M; Kretzschmar, J; Kreutzfeldt, K; Krieger, P; Kroeninger, K; Kroha, H; Kroll, J; Kroseberg, J; Krstic, J; Kruchonak, U; Krüger, H; Kruker, T; Krumnack, N; Krumshteyn, Z V; Kruse, A; Kruse, M C; Kruskal, M; Kubota, T; Kucuk, H; Kuday, S; Kuehn, S; Kugel, A; Kuhl, A; Kuhl, T; Kukhtin, V; Kulchitsky, Y; Kuleshov, S; Kuna, M; Kunigo, T; Kupco, A; Kurashige, H; Kurochkin, Y A; Kurumida, R; Kus, V; Kuwertz, E S; Kuze, M; Kvita, J; Kyriazopoulos, D; La Rosa, A; La Rotonda, L; Lacasta, C; Lacava, F; Lacey, J; Lacker, H; Lacour, D; Lacuesta, V R; Ladygin, E; Lafaye, R; Laforge, B; Lagouri, T; Lai, S; Laier, H; Lambourne, L; Lammers, S; Lampen, C L; Lampl, W; Lançon, E; Landgraf, U; Landon, M P J; Lang, V S; Lankford, A J; Lanni, F; Lantzsch, K; Laplace, S; Lapoire, C; Laporte, J F; Lari, T; Manghi, F Lasagni; Lassnig, M; Laurelli, P; Lavrijsen, W; Law, A T; Laycock, P; Le Dortz, O; Le Guirriec, E; Le Menedeu, E; LeCompte, T; Ledroit-Guillon, F; Lee, C A; Lee, H; Lee, S C; Lee, L; Lefebvre, G; Lefebvre, M; Legger, F; Leggett, C; Lehan, A; Lehmann Miotto, G; Lei, X; Leight, W A; Leisos, A; Leister, A G; Leite, M A L; Leitner, R; Lellouch, D; Lemmer, B; Leney, K J C; Lenz, T; Lenzen, G; Lenzi, B; Leone, R; Leone, S; Leonidopoulos, C; Leontsinis, S; Leroy, C; Lester, C G; Lester, C M; Levchenko, M; Levêque, J; Levin, D; Levinson, L J; Levy, M; Lewis, A; Lewis, G H; Leyko, A M; Leyton, M; Li, B; Li, B; Li, H; Li, H L; Li, L; Li, L; Li, S; Li, Y; Liang, Z; Liao, H; Liberti, B; Lichard, P; Lie, K; Liebal, J; Liebig, W; Limbach, C; Limosani, A; Lin, S C; Lin, T H; Linde, F; Lindquist, B E; Linnemann, J T; Lipeles, E; Lipniacka, A; Lisovyi, M; Liss, T M; Lissauer, D; Lister, A; Litke, A M; Liu, B; Liu, D; Liu, J B; Liu, K; Liu, L; Liu, M; Liu, M; Liu, Y; Livan, M; Lleres, A; Llorente Merino, J; Lloyd, S L; Lo Sterzo, F; Lobodzinska, E; Loch, P; Lockman, W S; Loebinger, F K; Loevschall-Jensen, A E; Loginov, A; Lohse, T; Lohwasser, K; Lokajicek, M; Lombardo, V P; Long, B A; Long, J D; Long, R E; Lopes, L; Lopez Mateos, D; Lopez Paredes, B; Lopez Paz, I; Lorenz, J; Lorenzo Martinez, N; Losada, M; Loscutoff, P; Lou, X; Lounis, A; Love, J; Love, P A; Lowe, A J; Lu, F; Lu, N; Lubatti, H J; Luci, C; Lucotte, A; Luehring, F; Lukas, W; Luminari, L; Lundberg, O; Lund-Jensen, B; Lungwitz, M; Lynn, D; Lysak, R; Lytken, E; Ma, H; Ma, L L; Maccarrone, G; Macchiolo, A; Machado Miguens, J; Macina, D; Madaffari, D; Madar, R; Maddocks, H J; Mader, W F; Madsen, A; Maeno, M; Maeno, T; Maevskiy, A; Magradze, E; Mahboubi, K; Mahlstedt, J; Mahmoud, S; Maiani, C; Maidantchik, C; Maier, A A; Maio, A; Majewski, S; Makida, Y; Makovec, N; Mal, P; Malaescu, B; Malecki, Pa; Maleev, V P; Malek, F; Mallik, U; Malon, D; Malone, C; Maltezos, S; Malyshev, V M; Malyukov, S; Mamuzic, J; Mandelli, B; Mandelli, L; Mandić, I; Mandrysch, R; Maneira, J; Manfredini, A; Manhaes de Andrade Filho, L; Manjarres Ramos, J A; Mann, A; Manning, P M; Manousakis-Katsikakis, A; Mansoulie, B; Mantifel, R; Mapelli, L; March, L; Marchand, J F; Marchiori, G; Marcisovsky, M; Marino, C P; Marjanovic, M; Marroquim, F; Marsden, S P; Marshall, Z; Marti, L F; Marti-Garcia, S; Martin, B; Martin, B; Martin, T A; Martin, V J; Martin Dit Latour, B; Martinez, H; Martinez, M; Martin-Haugh, S; Martyniuk, A C; Marx, M; Marzano, F; Marzin, A; Masetti, L; Mashimo, T; Mashinistov, R; Masik, J; Maslennikov, A L; Massa, I; Massa, L; Massol, N; Mastrandrea, P; Mastroberardino, A; Masubuchi, T; Mättig, P; Mattmann, J; Maurer, J; Maxfield, S J; Maximov, D A; Mazini, R; Mazzaferro, L; Mc Goldrick, G; Mc Kee, S P; McCarn, A; McCarthy, R L; McCarthy, T G; McCubbin, N A; McFarlane, K W; Mcfayden, J A; Mchedlidze, G; McMahon, S J; McPherson, R A; Mechnich, J; Medinnis, M; Meehan, S; Mehlhase, S; Mehta, A; Meier, K; Meineck, C; Meirose, B; Melachrinos, C; Mellado Garcia, B R; Meloni, F; Mengarelli, A; Menke, S; Meoni, E; Mercurio, K M; Mergelmeyer, S; Meric, N; Mermod, P; Merola, L; Meroni, C; Merritt, F S; Merritt, H; Messina, A; Metcalfe, J; Mete, A S; Meyer, C; Meyer, C; Meyer, J-P; Meyer, J; Middleton, R P; Migas, S; Miglioranzi, S; Mijović, L; Mikenberg, G; Mikestikova, M; Mikuž, M; Milic, A; Miller, D W; Mills, C; Milov, A; Milstead, D A; Minaenko, A A; Minami, Y; Minashvili, I A; Mincer, A I; Mindur, B; Mineev, M; Ming, Y; Mir, L M; Mirabelli, G; Mitani, T; Mitrevski, J; Mitsou, V A; Miucci, A; Miyagawa, P S; Mjörnmark, J U; Moa, T; Mochizuki, K; Mohapatra, S; Mohr, W; Molander, S; Moles-Valls, R; Mönig, K; Monini, C; Monk, J; Monnier, E; Montejo Berlingen, J; Monticelli, F; Monzani, S; Moore, R W; Morange, N; Moreno, D; Moreno Llácer, M; Morettini, P; Morgenstern, M; Morii, M; Morisbak, V; Moritz, S; Morley, A K; Mornacchi, G; Morris, J D; Morton, A; Morvaj, L; Moser, H G; Mosidze, M; Moss, J; Motohashi, K; Mount, R; Mountricha, E; Mouraviev, S V; Moyse, E J W; Muanza, S; Mudd, R D; Mueller, F; Mueller, J; Mueller, K; Mueller, T; Mueller, T; Muenstermann, D; Munwes, Y; Murillo Quijada, J A; Murray, W J; Musheghyan, H; Musto, E; Myagkov, A G; Myska, M; Nackenhorst, O; Nadal, J; Nagai, K; Nagai, R; Nagai, Y; Nagano, K; Nagarkar, A; Nagasaka, Y; Nagata, K; Nagel, M; Nairz, A M; Nakahama, Y; Nakamura, K; Nakamura, T; Nakano, I; Namasivayam, H; Nanava, G; Naranjo Garcia, R F; Narayan, R; Nattermann, T; Naumann, T; Navarro, G; Nayyar, R; Neal, H A; Nechaeva, P Yu; Neep, T J; Nef, P D; Negri, A; Negri, G; Negrini, M; Nektarijevic, S; Nellist, C; Nelson, A; Nelson, T K; Nemecek, S; Nemethy, P; Nepomuceno, A A; Nessi, M; Neubauer, M S; Neumann, M; Neves, R M; Nevski, P; Newman, P R; Nguyen, D H; Nickerson, R B; Nicolaidou, R; Nicquevert, B; Nielsen, J; Nikiforou, N; Nikiforov, A; Nikolaenko, V; Nikolic-Audit, I; Nikolics, K; Nikolopoulos, K; Nilsson, P; Ninomiya, Y; Nisati, A; Nisius, R; Nobe, T; Nodulman, L; Nomachi, M; Nomidis, I; Norberg, S; Nordberg, M; Novgorodova, O; Nowak, S; Nozaki, M; Nozka, L; Ntekas, K; Nunes Hanninger, G; Nunnemann, T; Nurse, E; Nuti, F; O'Brien, B J; O'grady, F; O'Neil, D C; O'Shea, V; Oakham, F G; Oberlack, H; Obermann, T; Ocariz, J; Ochi, A; Ochoa, M I; Oda, S; Odaka, S; Ogren, H; Oh, A; Oh, S H; Ohm, C C; Ohman, H; Oide, H; Okamura, W; Okawa, H; Okumura, Y; Okuyama, T; Olariu, A; Olchevski, A G; Olivares Pino, S A; Oliveira Damazio, D; Oliver Garcia, E; Olszewski, A; Olszowska, J; Onofre, A; Onyisi, P U E; Oram, C J; Oreglia, M J; Oren, Y; Orestano, D; Orlando, N; Oropeza Barrera, C; Orr, R S; Osculati, B; Ospanov, R; Otero Y Garzon, G; Otono, H; Ouchrif, M; Ouellette, E A; Ould-Saada, F; Ouraou, A; Oussoren, K P; Ouyang, Q; Ovcharova, A; Owen, M; Ozcan, V E; Ozturk, N; Pachal, K; Pacheco Pages, A; Padilla Aranda, C; Pagáčová, M; Pagan Griso, S; Paganis, E; Pahl, C; Paige, F; Pais, P; Pajchel, K; Palacino, G; Palestini, S; Palka, M; Pallin, D; Palma, A; Palmer, J D; Pan, Y B; Panagiotopoulou, E; Panduro Vazquez, J G; Pani, P; Panikashvili, N; Panitkin, S; Pantea, D; Paolozzi, L; Papadopoulou, Th D; Papageorgiou, K; Paramonov, A; Paredes Hernandez, D; Parker, M A; Parodi, F; Parsons, J A; Parzefall, U; Pasqualucci, E; Passaggio, S; Passeri, A; Pastore, F; Pastore, Fr; Pásztor, G; Pataraia, S; Patel, N D; Pater, J R; Patricelli, S; Pauly, T; Pearce, J; Pedersen, L E; Pedersen, M; Pedraza Lopez, S; Pedro, R; Peleganchuk, S V; Pelikan, D; Peng, H; Penning, B; Penwell, J; Perepelitsa, D V; Perez Codina, E; Pérez García-Estañ, M T; Perini, L; Pernegger, H; Perrella, S; Perrino, R; Peschke, R; Peshekhonov, V D; Peters, K; Peters, R F Y; Petersen, B A; Petersen, T C; Petit, E; Petridis, A; Petridou, C; Petrolo, E; Petrucci, F; Pettersson, N E; Pezoa, R; Phillips, P W; Piacquadio, G; Pianori, E; Picazio, A; Piccaro, E; Piccinini, M; Piegaia, R; Pignotti, D T; Pilcher, J E; Pilkington, A D; Pina, J; Pinamonti, M; Pinder, A; Pinfold, J L; Pingel, A; Pinto, B; Pires, S; Pitt, M; Pizio, C; Plazak, L; Pleier, M-A; Pleskot, V; Plotnikova, E; Plucinski, P; Pluth, D; Poddar, S; Podlyski, F; Poettgen, R; Poggioli, L; Pohl, D; Pohl, M; Polesello, G; Policicchio, A; Polifka, R; Polini, A; Pollard, C S; Polychronakos, V; Pommès, K; Pontecorvo, L; Pope, B G; Popeneciu, G A; Popovic, D S; Poppleton, A; Portell Bueso, X; Pospisil, S; Potamianos, K; Potrap, I N; Potter, C J; Potter, C T; Poulard, G; Poveda, J; Pozdnyakov, V; Pralavorio, P; Pranko, A; Prasad, S; Pravahan, R; Prell, S; Price, D; Price, J; Price, L E; Prieur, D; Primavera, M; Proissl, M; Prokofiev, K; Prokoshin, F; Protopapadaki, E; Protopopescu, S; Proudfoot, J; Przybycien, M; Przysiezniak, H; Ptacek, E; Puddu, D; Pueschel, E; Puldon, D; Purohit, M; Puzo, P; Qian, J; Qin, G; Qin, Y; Quadt, A; Quarrie, D R; Quayle, W B; Queitsch-Maitland, M; Quilty, D; Qureshi, A; Radeka, V; Radescu, V; Radhakrishnan, S K; Radloff, P; Rados, P; Ragusa, F; Rahal, G; Rajagopalan, S; Rammensee, M; Rangel-Smith, C; Rao, K; Rauscher, F; Rave, T C; Ravenscroft, T; Raymond, M; Read, A L; Readioff, N P; Rebuzzi, D M; Redelbach, A; Redlinger, G; Reece, R; Reeves, K; Rehnisch, L; Reisin, H; Relich, M; Rembser, C; Ren, H; Ren, Z L; Renaud, A; Rescigno, M; Resconi, S; Rezanova, O L; Reznicek, P; Rezvani, R; Richter, R; Ridel, M; Rieck, P; Rieger, J; Rijssenbeek, M; Rimoldi, A; Rinaldi, L; Ritsch, E; Riu, I; Rizatdinova, F; Rizvi, E; Robertson, S H; Robichaud-Veronneau, A; Robinson, D; Robinson, J E M; Robson, A; Roda, C; Rodrigues, L; Roe, S; Røhne, O; Rolli, S; Romaniouk, A; Romano, M; Romero Adam, E; Rompotis, N; Ronzani, M; Roos, L; Ros, E; Rosati, S; Rosbach, K; Rose, M; Rose, P; Rosendahl, P L; Rosenthal, O; Rossetti, V; Rossi, E; Rossi, L P; Rosten, R; Rotaru, M; Roth, I; Rothberg, J; Rousseau, D; Royon, C R; Rozanov, A; Rozen, Y; Ruan, X; Rubbo, F; Rubinskiy, I; Rud, V I; Rudolph, C; Rudolph, M S; Rühr, F; Ruiz-Martinez, A; Rurikova, Z; Rusakovich, N A; Ruschke, A; Russell, H L; Rutherfoord, J P; Ruthmann, N; Ryabov, Y F; Rybar, M; Rybkin, G; Ryder, N C; Saavedra, A F; Sabato, G; Sacerdoti, S; Saddique, A; Sadeh, I; Sadrozinski, H F-W; Sadykov, R; Safai Tehrani, F; Sakamoto, H; Sakurai, Y; Salamanna, G; Salamon, A; Saleem, M; Salek, D; Sales De Bruin, P H; Salihagic, D; Salnikov, A; Salt, J; Salvatore, D; Salvatore, F; Salvucci, A; Salzburger, A; Sampsonidis, D; Sanchez, A; Sánchez, J; Sanchez Martinez, V; Sandaker, H; Sandbach, R L; Sander, H G; Sanders, M P; Sandhoff, M; Sandoval, T; Sandoval, C; Sandstroem, R; Sankey, D P C; Sansoni, A; Santoni, C; Santonico, R; Santos, H; Santoyo Castillo, I; Sapp, K; Sapronov, A; Saraiva, J G; Sarrazin, B; Sartisohn, G; Sasaki, O; Sasaki, Y; Sauvage, G; Sauvan, E; Savard, P; Savu, D O; Sawyer, C; Sawyer, L; Saxon, D H; Saxon, J; Sbarra, C; Sbrizzi, A; Scanlon, T; Scannicchio, D A; Scarcella, M; Scarfone, V; Schaarschmidt, J; Schacht, P; Schaefer, D; Schaefer, R; Schaepe, S; Schaetzel, S; Schäfer, U; Schaffer, A C; Schaile, D; Schamberger, R D; Scharf, V; Schegelsky, V A; Scheirich, D; Schernau, M; Scherzer, M I; Schiavi, C; Schieck, J; Schillo, C; Schioppa, M; Schlenker, S; Schmidt, E; Schmieden, K; Schmitt, C; Schmitt, S; Schneider, B; Schnellbach, Y J; Schnoor, U; Schoeffel, L; Schoening, A; Schoenrock, B D; Schorlemmer, A L S; Schott, M; Schouten, D; Schovancova, J; Schramm, S; Schreyer, M; Schroeder, C; Schuh, N; Schultens, M J; Schultz-Coulon, H-C; Schulz, H; Schumacher, M; Schumm, B A; Schune, Ph; Schwanenberger, C; Schwartzman, A; Schwarz, T A; Schwegler, Ph; Schwemling, Ph; Schwienhorst, R; Schwindling, J; Schwindt, T; Schwoerer, M; Sciacca, F G; Scifo, E; Sciolla, G; Scuri, F; Scutti, F; Searcy, J; Sedov, G; Sedykh, E; Seema, P; Seidel, S C; Seiden, A; Seifert, F; Seixas, J M; Sekhniaidze, G; Sekula, S J; Selbach, K E; Seliverstov, D M; Sellers, G; Semprini-Cesari, N; Serfon, C; Serin, L; Serkin, L; Serre, T; Seuster, R; Severini, H; Sfiligoj, T; Sforza, F; Sfyrla, A; Shabalina, E; Shamim, M; Shan, L Y; Shang, R; Shank, J T; Shapiro, M; Shatalov, P B; Shaw, K; Shehu, C Y; Sherwood, P; Shi, L; Shimizu, S; Shimmin, C O; Shimojima, M; Shiyakova, M; Shmeleva, A; Saadi, D Shoaleh; Shochet, M J; Short, D; Shrestha, S; Shulga, E; Shupe, M A; Shushkevich, S; Sicho, P; Sidiropoulou, O; Sidorov, D; Sidoti, A; Siegert, F; Sijacki, Dj; Silva, J; Silver, Y; Silverstein, D; Silverstein, S B; Simak, V; Simard, O; Simic, Lj; Simion, S; Simioni, E; Simmons, B; Simon, D; Simoniello, R; Sinervo, P; Sinev, N B; Siragusa, G; Sircar, A; Sisakyan, A N; Sivoklokov, S Yu; Sjölin, J; Sjursen, T B; Skottowe, H P; Skovpen, K Yu; Skubic, P; Slater, M; Slavicek, T; Slawinska, M; Sliwa, K; Smakhtin, V; Smart, B H; Smestad, L; Smirnov, S Yu; Smirnov, Y; Smirnova, L N; Smirnova, O; Smith, K M; Smizanska, M; Smolek, K; Snesarev, A A; Snidero, G; Snyder, S; Sobie, R; Socher, F; Soffer, A; Soh, D A; Solans, C A; Solar, M; Solc, J; Soldatov, E Yu; Soldevila, U; Solodkov, A A; Soloshenko, A; Solovyanov, O V; Solovyev, V; Sommer, P; Song, H Y; Soni, N; Sood, A; Sopczak, A; Sopko, B; Sopko, V; Sorin, V; Sosebee, M; Soualah, R; Soueid, P; Soukharev, A M; South, D; Spagnolo, S; Spanò, F; Spearman, W R; Spettel, F; Spighi, R; Spigo, G; Spiller, L A; Spousta, M; Spreitzer, T; Denis, R D St; Staerz, S; Stahlman, J; Stamen, R; Stamm, S; Stanecka, E; Stanek, R W; Stanescu, C; Stanescu-Bellu, M; Stanitzki, M M; Stapnes, S; Starchenko, E A; Stark, J; Staroba, P; Starovoitov, P; Staszewski, R; Stavina, P; Steinberg, P; Stelzer, B; Stelzer, H J; Stelzer-Chilton, O; Stenzel, H; Stern, S; Stewart, G A; Stillings, J A; Stockton, M C; Stoebe, M; Stoicea, G; Stolte, P; Stonjek, S; Stradling, A R; Straessner, A; Stramaglia, M E; Strandberg, J; Strandberg, S; Strandlie, A; Strauss, E; Strauss, M; Strizenec, P; Ströhmer, R; Strom, D M; Stroynowski, R; Strubig, A; Stucci, S A; Stugu, B; Styles, N A; Su, D; Su, J; Subramaniam, R; Succurro, A; Sugaya, Y; Suhr, C; Suk, M; Sulin, V V; Sultansoy, S; Sumida, T; Sun, S; Sun, X; Sundermann, J E; Suruliz, K; Susinno, G; Sutton, M R; Suzuki, Y; Svatos, M; Swedish, S; Swiatlowski, M; Sykora, I; Sykora, T; Ta, D; Taccini, C; Tackmann, K; Taenzer, J; Taffard, A; Tafirout, R; Taiblum, N; Takai, H; Takashima, R; Takeda, H; Takeshita, T; Takubo, Y; Talby, M; Talyshev, A A; Tam, J Y C; Tan, K G; Tanaka, J; Tanaka, R; Tanaka, S; Tanaka, S; Tanasijczuk, A J; Tannenwald, B B; Tannoury, N; Tapprogge, S; Tarem, S; Tarrade, F; Tartarelli, G F; Tas, P; Tasevsky, M; Tashiro, T; Tassi, E; Tavares Delgado, A; Tayalati, Y; Taylor, F E; Taylor, G N; Taylor, W; Teischinger, F A; Teixeira Dias Castanheira, M; Teixeira-Dias, P; Temming, K K; Ten Kate, H; Teng, P K; Teoh, J J; Terada, S; Terashi, K; Terron, J; Terzo, S; Testa, M; Teuscher, R J; Therhaag, J; Theveneaux-Pelzer, T; Thomas, J P; Thomas-Wilsker, J; Thompson, E N; Thompson, P D; Thompson, P D; Thompson, R J; Thompson, A S; Thomsen, L A; Thomson, E; Thomson, M; Thong, W M; Thun, R P; Tian, F; Tibbetts, M J; Tikhomirov, V O; Tikhonov, Yu A; Timoshenko, S; Tiouchichine, E; Tipton, P; Tisserant, S; Todorov, T; Todorova-Nova, S; Tojo, J; Tokár, S; Tokushuku, K; Tollefson, K; Tolley, E; Tomlinson, L; Tomoto, M; Tompkins, L; Toms, K; Topilin, N D; Torrence, E; Torres, H; Torró Pastor, E; Toth, J; Touchard, F; Tovey, D R; Tran, H L; Trefzger, T; Tremblet, L; Tricoli, A; Trigger, I M; Trincaz-Duvoid, S; Tripiana, M F; Trischuk, W; Trocmé, B; Troncon, C; Trottier-McDonald, M; Trovatelli, M; True, P; Trzebinski, M; Trzupek, A; Tsarouchas, C; Tseng, J C-L; Tsiareshka, P V; Tsionou, D; Tsipolitis, G; Tsirintanis, N; Tsiskaridze, S; Tsiskaridze, V; Tskhadadze, E G; Tsukerman, I I; Tsulaia, V; Tsuno, S; Tsybychev, D; Tudorache, A; Tudorache, V; Tuna, A N; Tupputi, S A; Turchikhin, S; Turecek, D; Turk Cakir, I; Turra, R; Turvey, A J; Tuts, P M; Tykhonov, A; Tylmad, M; Tyndel, M; Uchida, K; Ueda, I; Ueno, R; Ughetto, M; Ugland, M; Uhlenbrock, M; Ukegawa, F; Unal, G; Undrus, A; Unel, G; Ungaro, F C; Unno, Y; Unverdorben, C; Urban, J; Urbaniec, D; Urquijo, P; Usai, G; Usanova, A; Vacavant, L; Vacek, V; Vachon, B; Valencic, N; Valentinetti, S; Valero, A; Valery, L; Valkar, S; Valladolid Gallego, E; Vallecorsa, S; Valls Ferrer, J A; Van Den Wollenberg, W; Van Der Deijl, P C; van der Geer, R; van der Graaf, H; Van Der Leeuw, R; van der Ster, D; van Eldik, N; van Gemmeren, P; Van Nieuwkoop, J; van Vulpen, I; van Woerden, M C; Vanadia, M; Vandelli, W; Vanguri, R; Vaniachine, A; Vankov, P; Vannucci, F; Vardanyan, G; Vari, R; Varnes, E W; Varol, T; Varouchas, D; Vartapetian, A; Varvell, K E; Vazeille, F; Vazquez Schroeder, T; Veatch, J; Veloso, F; Velz, T; Veneziano, S; Ventura, A; Ventura, D; Venturi, M; Venturi, N; Venturini, A; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, J C; Vest, A; Vetterli, M C; Viazlo, O; Vichou, I; Vickey, T; Vickey Boeriu, O E; Viehhauser, G H A; Viel, S; Vigne, R; Villa, M; Villaplana Perez, M; Vilucchi, E; Vincter, M G; Vinogradov, V B; Virzi, J; Vivarelli, I; Vives Vaque, F; Vlachos, S; Vladoiu, D; Vlasak, M; Vogel, A; Vogel, M; Vokac, P; Volpi, G; Volpi, M; von der Schmitt, H; von Radziewski, H; von Toerne, E; Vorobel, V; Vorobev, K; Vos, M; Voss, R; Vossebeld, J H; Vranjes, N; Vranjes Milosavljevic, M; Vrba, V; Vreeswijk, M; Vu Anh, T; Vuillermet, R; Vukotic, I; Vykydal, Z; Wagner, P; Wagner, W; Wahlberg, H; Wahrmund, S; Wakabayashi, J; Walder, J; Walker, R; Walkowiak, W; Wall, R; Waller, P; Walsh, B; Wang, C; Wang, C; Wang, F; Wang, H; Wang, H; Wang, J; Wang, J; Wang, K; Wang, R; Wang, S M; Wang, T; Wang, X; Wanotayaroj, C; Warburton, A; Ward, C P; Wardrope, D R; Warsinsky, M; Washbrook, A; Wasicki, C; Watkins, P M; Watson, A T; Watson, I J; Watson, M F; Watts, G; Watts, S; Waugh, B M; Webb, S; Weber, M S; Weber, S W; Webster, J S; Weidberg, A R; Weinert, B; Weingarten, J; Weiser, C; Weits, H; Wells, P S; Wenaus, T; Wendland, D; Weng, Z; Wengler, T; Wenig, S; Wermes, N; Werner, M; Werner, P; Wessels, M; Wetter, J; Whalen, K; White, A; White, M J; White, R; White, S; Whiteson, D; Wicke, D; Wickens, F J; Wiedenmann, W; Wielers, M; Wienemann, P; Wiglesworth, C; Wiik-Fuchs, L A M; Wijeratne, P A; Wildauer, A; Wildt, M A; Wilkens, H G; Williams, H H; Williams, S; Willis, C; Willocq, S; Wilson, A; Wilson, J A; Wingerter-Seez, I; Winklmeier, F; Winter, B T; Wittgen, M; Wittig, T; Wittkowski, J; Wollstadt, S J; Wolter, M W; Wolters, H; Wosiek, B K; Wotschack, J; Woudstra, M J; Wozniak, K W; Wright, M; Wu, M; Wu, S L; Wu, X; Wu, Y; Wulf, E; Wyatt, T R; Wynne, B M; Xella, S; Xiao, M; Xu, D; Xu, L; Yabsley, B; Yacoob, S; Yakabe, R; Yamada, M; Yamaguchi, H; Yamaguchi, Y; Yamamoto, A; Yamamoto, S; Yamamura, T; Yamanaka, T; Yamauchi, K; Yamazaki, Y; Yan, Z; Yang, H; Yang, H; Yang, U K; Yang, Y; Yanush, S; Yao, L; Yao, W-M; Yasu, Y; Yatsenko, E; Yau Wong, K H; Ye, J; Ye, S; Yeletskikh, I; Yen, A L; Yildirim, E; Yilmaz, M; Yoosoofmiya, R; Yorita, K; Yoshida, R; Yoshihara, K; Young, C; Young, C J S; Youssef, S; Yu, D R; Yu, J; Yu, J M; Yu, J; Yuan, L; Yurkewicz, A; Yusuff, I; Zabinski, B; Zaidan, R; Zaitsev, A M; Zaman, A; Zambito, S; Zanello, L; Zanzi, D; Zeitnitz, C; Zeman, M; Zemla, A; Zengel, K; Zenin, O; Ženiš, T; Zerwas, D; Zevi Della Porta, G; Zhang, D; Zhang, F; Zhang, H; Zhang, J; Zhang, L; Zhang, R; Zhang, X; Zhang, Z; Zhao, Y; Zhao, Z; Zhemchugov, A; Zhong, J; Zhou, B; Zhou, L; Zhou, N; Zhu, C G; Zhu, H; Zhu, J; Zhu, Y; Zhuang, X; Zhukov, K; Zibell, A; Zieminska, D; Zimine, N I; Zimmermann, C; Zimmermann, R; Zimmermann, S; Zimmermann, S; Zinonos, Z; Ziolkowski, M; Zobernig, G; Zoccoli, A; Zur Nedden, M; Zurzolo, G; Zutshi, V; Zwalinski, L

This paper describes the trigger and offline reconstruction, identification and energy calibration algorithms for hadronic decays of tau leptons employed for the data collected from pp collisions in 2012 with the ATLAS detector at the LHC center-of-mass energy [Formula: see text] [Formula: see text]. The performance of these algorithms is measured in most cases with [Formula: see text] decays to tau leptons using the full 2012 dataset, corresponding to an integrated luminosity of 20.3 fb[Formula: see text]. An uncertainty on the offline reconstructed tau energy scale of 2-4 %, depending on transverse energy and pseudorapidity, is achieved using two independent methods. The offline tau identification efficiency is measured with a precision of 2.5 % for hadronically decaying tau leptons with one associated track, and of 4 % for the case of three associated tracks, inclusive in pseudorapidity and for a visible transverse energy greater than 20 [Formula: see text]. For hadronic tau lepton decays selected by offline algorithms, the tau trigger identification efficiency is measured with a precision of 2-8 %, depending on the transverse energy. The performance of the tau algorithms, both offline and at the trigger level, is found to be stable with respect to the number of concurrent proton-proton interactions and has supported a variety of physics results using hadronically decaying tau leptons at ATLAS.

Searching for ultra high energy neutrinos from space

NASA Astrophysics Data System (ADS)

Santangelo, A.

2006-07-01

Observations of neutrinos at Ultra High Energies (UHE), from a few 1018 eV to beyond the decade of 1020 eV, are an extraordinary opportunity to explore this still largely unknown Universe and present us a tremendous experimental challenge. It is indeed expected that observations of UHEνs (and cosmic rays) will provide entirely new information on the sources and on the physical mechanisms able to accelerate these extreme messengers to macroscopic energies. However, as extensively debated in the last few years, UHE particles might, also, carry evidence of unknown physics or of exotic particles, relics of the early Universe. To reach these goals, high statistics, high quality observations are required. This implies innovative experiments with larger acceptances and good understanding of systematic uncertainties. The ground-based Pierre Auger Observatory, whose southern site is expected to be completed in Malargue, Argentina by the end of 2006, will surely provide, in the near future, a more solid observational scenario for UHE Cosmic Rays (UHECR). However, only space-based observatories can reach the effective area necessary to systematically explore the UHE universe. Space-based observatories are likely to be essential for neutrino observations at UHE. In fact only a few UHE neutrinos will be detected by the current planned observatories and only if the most promising estimates for fluxes applies. In the present paper, after summarizing the science rationale behind UHEν studies, we review the status of current experimental efforts, with the main emphasis on the actual generation of space-based observatories. We also briefly discuss the scientific goals, the requirements and the R&D of a “next-generation” space-based mission for UHE observations. The opening of the ESA “Cosmic Vision 2015 2025” long term plan provides, in the very near future, an unique opportunity to develop such a challenging and innovative observatory for UHE.

Analysis of stationary fuel cell dynamic ramping capabilities and ultra capacitor energy storage using high resolution demand data

NASA Astrophysics Data System (ADS)

Meacham, James R.; Jabbari, Faryar; Brouwer, Jacob; Mauzey, Josh L.; Samuelsen, G. Scott

Current high temperature fuel cell (HTFC) systems used for stationary power applications (in the 200-300 kW size range) have very limited dynamic load following capability or are simply base load devices. Considering the economics of existing electric utility rate structures, there is little incentive to increase HTFC ramping capability beyond 1 kWs -1 (0.4% s -1). However, in order to ease concerns about grid instabilities from utility companies and increase market adoption, HTFC systems will have to increase their ramping abilities, and will likely have to incorporate electrical energy storage (EES). Because batteries have low power densities and limited lifetimes in highly cyclic applications, ultra capacitors may be the EES medium of choice. The current analyses show that, because ultra capacitors have a very low energy storage density, their integration with HTFC systems may not be feasible unless the fuel cell has a ramp rate approaching 10 kWs -1 (4% s -1) when using a worst-case design analysis. This requirement for fast dynamic load response characteristics can be reduced to 1 kWs -1 by utilizing high resolution demand data to properly size ultra capacitor systems and through demand management techniques that reduce load volatility.

On the maximum energy of shock-accelerated cosmic rays at ultra-relativistic shocks

NASA Astrophysics Data System (ADS)

Reville, B.; Bell, A. R.

2014-04-01

The maximum energy to which cosmic rays can be accelerated at weakly magnetised ultra-relativistic shocks is investigated. We demonstrate that for such shocks, in which the scattering of energetic particles is mediated exclusively by ion skin-depth scale structures, as might be expected for a Weibel-mediated shock, there is an intrinsic limit on the maximum energy to which particles can be accelerated. This maximum energy is determined from the requirement that particles must be isotropized in the downstream plasma frame before the mean field transports them far downstream, and falls considerably short of what is required to produce ultra-high-energy cosmic rays. To circumvent this limit, a highly disorganized field is required on larger scales. The growth of cosmic ray-induced instabilities on wavelengths much longer than the ion-plasma skin depth, both upstream and downstream of the shock, is considered. While these instabilities may play an important role in magnetic field amplification at relativistic shocks, on scales comparable to the gyroradius of the most energetic particles, the calculated growth rates have insufficient time to modify the scattering. Since strong modification is a necessary condition for particles in the downstream region to re-cross the shock, in the absence of an alternative scattering mechanism, these results imply that acceleration to higher energies is ruled out. If weakly magnetized ultra-relativistic shocks are disfavoured as high-energy particle accelerators in general, the search for potential sources of ultra-high-energy cosmic rays can be narrowed.

Study of ultra-high energy emission from Cygnus X-3 and Hercules X-1

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

Dingus, B.L.

1988-11-01

The CYGNUS experiment, consisting of an extensive air shower detector and a muon detector, was built at Los Alamos, New Mexico (latitude 36 N, longitude 107W, altitude 2310 meters), to search for point sources of ultra-high energy (>10/sup 14/ eV) particles. These particles must be long-lived neutral particles because of the long source distances and the presence of the intragalactic magnetic field. Gamma rays are the most likely candidates because of the short neutron lifetime and the small neutrino cross section. Therefore, the muon content of the source showers is examined to determine if these events are muon poor asmore » is expected for gamma-initiated showers. The data set from April 1986 to July 1987 is searched for continual emission from Cygnus X-3 and Hercules X-1, and an upper bound to flux is determined for both sources. The flux limit for Cygnus X-3, 2.0 /times/ 10/sup /minus/13/ cm/sup /minus/2/ sec/sup /minus/1/ above 50 TeV, is lower than previous ultra-high energy observations. Hercules X-1 has never been observed continually at ultra-high energies. Cygnus X-3 is observed for a shorter interval of time, beginning on 17 April 1986 and ending 1 June 1986. There is one chance in 300 that the observation is due to a random fluctuation. The signal is correlated with the 4.8 hour orbital period, and the muon content of the showers in the signal is inconsistent with the conventional prediction of gamma- initiated showers. An episodic signal is also reported for Hercules X-1, and it consists of two bursts of less than one hour duration on 24 July 1986. The probability is one chance in 12,000 that this observation is not associated with Hercules X-1. The signal is pulsed at frequency near, but significantly different from, the x-ray pulsar frequency. The muon content of the signal showers is also anomalous, assuming the showers are initiated by gamma rays. 62 refs., 60 figs.« less

Concept and Analysis of a Satellite for Space-Based Radio Detection of Ultra-High Energy Cosmic Rays

NASA Astrophysics Data System (ADS)

Romero-Wolf, Andrew; Gorham, P.; Booth, J.; Chen, P.; Duren, R. M.; Liewer, K.; Nam, J.; Saltzberg, D.; Schoorlemmer, H.; Wissel, S.; Zairfian, P.

2014-01-01

We present a concept for on-orbit radio detection of ultra-high energy cosmic rays (UHECRs) that has the potential to provide collection rates of ~100 events per year for energies above 10^20 eV. The synoptic wideband orbiting radio detector (SWORD) mission's high event statistics at these energies combined with the pointing capabilities of a space-borne antenna array could enable charged particle astronomy. The detector concept is based on ANITA's successful detection UHECRs where the geosynchrotron radio signal produced by the extended air shower is reflected off the Earth's surface and detected in flight.

HOW MANY ULTRA-HIGH ENERGY COSMIC RAYS COULD WE EXPECT FROM CENTAURUS A?

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

Fraija, N.; Gonzalez, M. M.; Perez, M.

2012-07-01

The Pierre Auger Observatory has associated a few ultra-high energy cosmic rays (UHECRs) with the direction of Centaurus A. This source has been deeply studied in radio, infrared, X-ray, and {gamma}-rays (MeV-TeV) because it is the nearest radio-loud active galactic nucleus. Its spectral energy distribution or spectrum shows two main peaks, the low-energy peak, at an energy of 10{sup -2} eV, and the high-energy peak, at about 150 keV. There is also a faint very high energy (VHE; E {>=} 100 GeV) {gamma}-ray emission fully detected by the High Energy Stereoscopic System experiment. In this work, we describe the entiremore » spectrum: the two main peaks with a synchrotron/synchrotron self-Compton model, and the VHE emission with a hadronic model. We consider p{gamma} and pp interactions. For the p{gamma} interaction, we assume that the target photons are those produced at 150 keV in leptonic processes. On the other hand, for the pp interaction we consider as targets the thermal particle densities in the lobes. Requiring a satisfactory description of the spectra at very high energies with p{gamma} interaction, we obtain an excessive luminosity in UHECRs (even exceeding the Eddington luminosity). However, when considering the pp interaction to describe the {gamma}-spectrum, the number of UHECRs obtained is in agreement with Pierre Auger observations. We also calculate the possible neutrino signal from pp interactions on a Km{sup 3} neutrino telescope using Monte Carlo simulations.« less

Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets

PubMed Central

Zhou, Lili; Summa, Keith C.; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.

2016-01-01

Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε −/− and CK1ε tau/tau mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1ε tau/tau mice on a 24 hr LD cycle, a separate set of CK1ε tau/tau mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1ε −/− and CK1ε tau/tau mutants on a 24 hr LD cycle and CK1ε tau/tau mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1ε tau/tau mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. PMID:27144030

Magnetic Microcalorimeter (MMC) Gamma Detectors with Ultra-High Energy Resolution

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

Friedrich, Stephen

The goal of this LCP is to develop ultra-high resolution gamma detectors based on magnetic microcalorimeters (MMCs) for accurate non-destructive analysis (NDA) of nuclear materials. For highest energy resolution, we will introduce erbium-doped silver (Ag:Er) as a novel sensor material, and implement several geometry and design changes to improve the signal-to-noise ratio. The detector sensitivity will be increased by developing arrays of 32 Ag:Er pixels read out by 16 SQUID preamplifiers, and by developing a cryogenic Compton veto to reduce the spectral background. Since best MMC performance requires detector operation at ~10 mK, we will purchase a dilution refrigerator withmore » a base temperature <10 mK and adapt it for MMC operation. The detector performance will be tested with radioactive sources of interest to the safeguards community.« less

Ultra-high spatial resolution multi-energy CT using photon counting detector technology

NASA Astrophysics Data System (ADS)

Leng, S.; Gutjahr, R.; Ferrero, A.; Kappler, S.; Henning, A.; Halaweish, A.; Zhou, W.; Montoya, J.; McCollough, C.

2017-03-01

Two ultra-high-resolution (UHR) imaging modes, each with two energy thresholds, were implemented on a research, whole-body photon-counting-detector (PCD) CT scanner, referred to as sharp and UHR, respectively. The UHR mode has a pixel size of 0.25 mm at iso-center for both energy thresholds, with a collimation of 32 × 0.25 mm. The sharp mode has a 0.25 mm pixel for the low-energy threshold and 0.5 mm for the high-energy threshold, with a collimation of 48 × 0.25 mm. Kidney stones with mixed mineral composition and lung nodules with different shapes were scanned using both modes, and with the standard imaging mode, referred to as macro mode (0.5 mm pixel and 32 × 0.5 mm collimation). Evaluation and comparison of the three modes focused on the ability to accurately delineate anatomic structures using the high-spatial resolution capability and the ability to quantify stone composition using the multi-energy capability. The low-energy threshold images of the sharp and UHR modes showed better shape and texture information due to the achieved higher spatial resolution, although noise was also higher. No noticeable benefit was shown in multi-energy analysis using UHR compared to standard resolution (macro mode) when standard doses were used. This was due to excessive noise in the higher resolution images. However, UHR scans at higher dose showed improvement in multi-energy analysis over macro mode with regular dose. To fully take advantage of the higher spatial resolution in multi-energy analysis, either increased radiation dose, or application of noise reduction techniques, is needed.

Ultra-compact Marx-type high-voltage generator

DOEpatents

Goerz, David A.; Wilson, Michael J.

2000-01-01

An ultra-compact Marx-type high-voltage generator includes individual high-performance components that are closely coupled and integrated into an extremely compact assembly. In one embodiment, a repetitively-switched, ultra-compact Marx generator includes low-profile, annular-shaped, high-voltage, ceramic capacitors with contoured edges and coplanar extended electrodes used for primary energy storage; low-profile, low-inductance, high-voltage, pressurized gas switches with compact gas envelopes suitably designed to be integrated with the annular capacitors; feed-forward, high-voltage, ceramic capacitors attached across successive switch-capacitor-switch stages to couple the necessary energy forward to sufficiently overvoltage the spark gap of the next in-line switch; optimally shaped electrodes and insulator surfaces to reduce electric field stresses in the weakest regions where dissimilar materials meet, and to spread the fields more evenly throughout the dielectric materials, allowing them to operate closer to their intrinsic breakdown levels; and uses manufacturing and assembly methods to integrate the capacitors and switches into stages that can be arranged into a low-profile Marx generator.

Advanced technique for ultra-thin residue inspection with sub-10nm thickness using high-energy back-scattered electrons

NASA Astrophysics Data System (ADS)

Han, Jin-Hee

2018-03-01

Recently the aspect ratio of capacitor and via hole of memory semiconductor device has been dramatically increasing in order to store more information in a limited area. A small amount of remained residues after etch process on the bottom of the high aspect ratio structure can make a critical failure in device operation. Back-scattered electrons (BSE) are mainly used for inspecting the defect located at the bottom of the high aspect ratio structure or analyzing the overlay of the multi-layer structure because these electrons have a high linearity with the direction of emission and a high kinetic energy above 50eV. However, there is a limitation on that it cannot detect ultra-thin residue material having a thickness of several nanometers because the surface sensitivity is extremely low. We studied the characteristics of BSE spectra using Monte Carlo simulations for several cases which the high aspect ratio structures have extreme microscopic residues. Based on the assumption that most of the electrons emitted without energy loss are localized on the surface, we selected the detection energy window which has a range of 20eV below the maximum energy of the BSE. This window section is named as the high-energy BSE region. As a result of comparing the detection sensitivity of the conventional and the high-energy BSE detection mode, we found that the detection sensitivity for the residuals which have 2nm thickness is improved by more than 10 times in the high-energy BSE mode. This BSE technology is a new inspection method that can greatly be improved the inspection sensitivity for the ultra-thin residual material presented in the high aspect ratio structure, and its application will be expanded.

Telescope Array Radar (TARA) Observatory for Ultra-High Energy Cosmic Rays

DOE PAGES

Abbasi, R.; Takai, H.; Allen, C.; ...

2014-08-19

Construction was completed during summer 2013 on the Telescope Array RAdar (TARA) bi-static radar observatory for Ultra-High Energy Cosmic Rays (UHECR). TARA is co-located with the Telescope Array, the largest “conventional” cosmic ray detector in the Northern Hemisphere, in radio-quiet Western Utah. TARA employs an 8 MW Effective Radiated Power (ERP) VHF transmitter and smart receiver system based on a 250 MS/s data acquisition system in an effort to detect the scatter of sounding radiation by UHECR-induced atmospheric ionization. TARA seeks to demonstrate bi-static radar as a useful new remote sensing technique for UHECRs. In this report, we describe themore » design and performance of the TARA transmitter and receiver systems.« less

Shock waves raised by explosions in space as sources of ultra-high-energy cosmic rays

NASA Astrophysics Data System (ADS)

Kichigin, Gennadiy

2015-03-01

The paper discusses the possibility of particle acceleration up to ultrahigh energies in the relativistic waves generated by various explosive processes in the interstellar medium. We propose to use the surfatron mechanism of acceleration (surfing) of charged particles trapped in the front of relativistic waves as a generator of high-energy cosmic rays (CRs). Conditions under which surfing in these waves can be made are studied thoroughly. Ultra-high-energy CRs (up to 10^20 eV) are shown to be obtained due to the surfing in the relativistic plane and spherical waves. Surfing is supposed to take place in nonlinear Langmuir waves excited by powerful electromagnetic radiation or relativistic beams of charged particles, as well as in strong shock waves generated by relativistic jets or spherical formations that expand fast (fireballs).

Identification and energy calibration of hadronically decaying tau leptons with the ATLAS experiment in pp collisions at $$\\sqrt{s}=8$$ $$\\,\\hbox {TeV}$$ TeV

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2015-07-02

This study describes the trigger and offline reconstruction, identification and energy calibration algorithms for hadronic decays of tau leptons employed for the data collected from pp collisions in 2012 with the ATLAS detector at the LHC center-of-mass energy √s=8 TeV. The performance of these algorithms is measured in most cases with Z decays to tau leptons using the full 2012 dataset, corresponding to an integrated luminosity of 20.3 fb –1. An uncertainty on the offline reconstructed tau energy scale of 2–4%, depending on transverse energy and pseudorapidity, is achieved using two independent methods. The offline tau identification efficiency is measuredmore » with a precision of 2.5% for hadronically decaying tau leptons with one associated track, and of 4% for the case of three associated tracks, inclusive in pseudorapidity and for a visible transverse energy greater than 20 GeV. For hadronic tau lepton decays selected by offline algorithms, the tau trigger identification efficiency is measured with a precision of 2–8%, depending on the transverse energy. The performance of the tau algorithms, both offline and at the trigger level, is found to be stable with respect to the number of concurrent proton–proton interactions and has supported a variety of physics results using hadronically decaying tau leptons at ATLAS.« less

High-energy and ultra-wideband tunable terahertz source with DAST crystal via difference frequency generation

NASA Astrophysics Data System (ADS)

He, Yixin; Wang, Yuye; Xu, Degang; Nie, Meitong; Yan, Chao; Tang, Longhuang; Shi, Jia; Feng, Jiachen; Yan, Dexian; Liu, Hongxiang; Teng, Bing; Feng, Hua; Yao, Jianquan

2018-01-01

We have demonstrated a high-energy and broadly tunable monochromatic terahertz (THz) source based on difference frequency generation (DFG) in DAST crystal. A high-energy dual-wavelength optical parametric oscillator with two KTP crystals was constructed as a light source for DFG, where the effect of blue light was first observed accompanying with tunable dual-wavelength pump light due to different nonlinear processes. The THz frequency was tuned randomly in the range of 0.3-19.6 THz. The highest energy of 870 nJ/pulse was obtained at 18.9 THz under the intense pump intensity of 247 MW/cm2. The THz energy dips above 3 THz have been analyzed and mainly attributed to the resonance absorption induced by lattice vibration in DAST crystal. The dependence of THz output on the input energy was studied experimentally, and THz output saturation was observed. Furthermore, tests of transmission spectroscopy of four typical samples were demonstrated with this ultra-wideband THz source.

A High-throughput Screening Assay for Determining Cellular Levels of Total Tau Protein

PubMed Central

Dehdashti, Seameen J.; Zheng, Wei; Gever, Joel R.; Wilhelm, Robert; Nguyen, Dac-Trung; Sittampalam, Gurusingham; McKew, John C.; Austin, Christopher P.; Prusiner, Stanley B.

2014-01-01

The microtubule-associated protein (MAP) tau has been implicated in the pathology of numerous neurodegenerative diseases. In the past decade, the hyperphosphorylated and aggregated states of tau protein have been important targets in the drug discovery field for the potential treatment of Alzheimer’s disease. Although several compounds have been reported to reduce the hyperphosphorylated state of tau or impact the stabilization of tau, their therapeutic activities are still to be validated. Recently, reduction of total cellular tau protein has emerged as an alternate intervention point for drug development and a potential treatment of tauopathies. We have developed and optimized a homogenous assay, using the AlphaLISA and HTRF assay technologies, for the quantification of total cellular tau protein levels in the SH-SY5Y neuroblastoma cell line. The signal-to-basal ratios were 375 and 5.3, and the Z’ factors were 0.67 and 0.60 for the AlphaLISA and HTRF tau assays, respectively. The clear advantages of this homogeneous tau assay over conventional total tau assays, such as ELISA and Western blot, are the elimination of plate wash steps and miniaturization of the assay into 1536-well plate format for the ultra–high-throughput screening of large compound libraries. PMID:23905996

Graphene and carbon nanotube composite electrodes for supercapacitors with ultra-high energy density.

PubMed

Cheng, Qian; Tang, Jie; Ma, Jun; Zhang, Han; Shinya, Norio; Qin, Lu-Chang

2011-10-21

We describe a graphene and single-walled carbon nanotube (SWCNT) composite film prepared by a blending process for use as electrodes in high energy density supercapacitors. Specific capacitances of 290.6 F g(-1) and 201.0 F g(-1) have been obtained for a single electrode in aqueous and organic electrolytes, respectively, using a more practical two-electrode testing system. In the organic electrolyte the energy density reached 62.8 Wh kg(-1) and the power density reached 58.5 kW kg(-1). The addition of single-walled carbon nanotubes raised the energy density by 23% and power density by 31% more than the graphene electrodes. The graphene/CNT electrodes exhibited an ultra-high energy density of 155.6 Wh kg(-1) in ionic liquid at room temperature. In addition, the specific capacitance increased by 29% after 1000 cycles in ionic liquid, indicating their excellent cyclicity. The SWCNTs acted as a conductive additive, spacer, and binder in the graphene/CNT supercapacitors. This work suggests that our graphene/CNT supercapacitors can be comparable to NiMH batteries in performance and are promising for applications in hybrid vehicles and electric vehicles. This journal is © the Owner Societies 2011

Observation of ultra high energy cosmic rays from space: Status and perspectives

NASA Astrophysics Data System (ADS)

Casolino, M.; Klimov, P.; Piotrowski, L.

2017-12-01

The study of ultra high energy cosmic rays (UHECRs) offers unique possibilities to probe the energies currently inaccessible by man-made accelerators. Recent years have shed light on several characteristics of these particles, but—due to their extremely low flux—their origin, nature, and acceleration mechanisms are still unclear. Space-based observations have the potential for an increase in statistics, up to several orders of magnitude, and would be able to cover the whole sky, allowing for a direct comparison of spectra and direction of arrival. A detector with the exposure of a few times that of the Pierre Auger Observatory would be able to clarify the observed differences between the northern and southern skies, confirm the existence of TA hot spot, and measure multipolar anisotropies with high precision. A number of novel technologies—from optics to sensors, front-end and read-out electronics—have been developed over the years to achieve this goal. In this paper we describe the progress and results obtained so far and discuss the perspectives of UHECR physics observation from space.

Vectored Intracerebral Immunization with the Anti-Tau Monoclonal Antibody PHF1 Markedly Reduces Tau Pathology in Mutant Tau Transgenic Mice.

PubMed

Liu, Wencheng; Zhao, Lingzhi; Blackman, Brittany; Parmar, Mayur; Wong, Man Ying; Woo, Thomas; Yu, Fangmin; Chiuchiolo, Maria J; Sondhi, Dolan; Kaminsky, Stephen M; Crystal, Ronald G; Paul, Steven M

2016-12-07

Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic administration. In contrast to systemic passive immunization, we observed markedly reduced (≥80-90%) hippocampal insoluble pathological tau species and neurofibrillary tangles following a single dose of AAV-vectored PHF1 compared with mice treated with an AAV-IgG control vector. Moreover, the hippocampal atrophy observed in untreated P301S mice was fully rescued by treatment with the AAV-vectored PHF1 antibody. Vectored passive immunotherapy with an anti-tau monoclonal antibody may represent a viable therapeutic strategy for treating or preventing such tauopathies as frontotemporal dementia, progressive supranuclear palsy, or Alzheimer's disease. We have used an adeno-associated viral (AAV) vector to deliver the genes encoding an anti-phospho-tau monoclonal antibody, PHF1, directly to the brain of mice that develop neurodegeneration due to a tau mutation that causes frontotemporal dementia (FTD). When administered systemically, PHF1 has been shown to modestly reduce tau pathology and neurodegeneration. Since such antibodies do not readily cross the blood-brain barrier, we used an AAV vector to deliver antibody directly to the hippocampus and observed much higher antibody levels and a much greater reduction in tau pathology. Using

The Microjet of AA Tau

NASA Astrophysics Data System (ADS)

Cox, A. W.; Hilton, G. M.; Williger, G. M.; Grady, C. A.; Woodgate, B.

2005-12-01

The microjet of AA Tau A.W. Cox (Atholton High School, Columbia MD), G.M. Hilton (SSAI and GSFC), G.M. Williger (JHU and U. Louisville), C.A. Grady (Eureka Scientific and GSFC) B.Woodgate (NASA's GSFC) AA Tau is a classical T Tauri star with a spatially resolved disk viewed at approximately 70 degrees from pole-on. Photo-polarimetric variability of the star has been interpreted as being caused by the stellar magnetic field being inclined at 30 degrees with respect to the stellar rotation axis, producing a warp in the inner disk. Under these conditions, any jet should be less collimated than typical of T Tauri microjets, and should show signs of the jet axis precessing around the stellar rotation axis. When compared with the microjets imaged in the HST/STIS coronagraphic imaging survey, the AA Tau jet has an opening half-angle of approximately 10-15 degrees rather than the 3-5 degrees typical of the other T Tauri stars which have been coronagraphically imaged by HST/STIS. Using the HST data with ultra-narrowband imagery and long slit spectroscopy obtained with the Goddard Fabry-Perot and the Dual Imaging Spectrograph at the Apache Point Observatory 3.5m telescope, we derive the jet inclination, knot ejection epochs, and ejection frequency. We also compare the jet opening angle with model predictions. Apache Point Observatory observations with the Goddard Fabry-Perot were made through a grant of Director's Discretionary Time. Apache Point Observatory is operated by the Astrophysical Research Consortium. The GFP was supported under NASA RTOP 51-188-01-22 to GSFC. Grady is supported under NASA contract NNH05CD30C to Eureka Scientific.

Disordering of ultra thin WO3 films by high-energy ions

NASA Astrophysics Data System (ADS)

Matsunami, N.; Kato, M.; Sataka, M.; Okayasu, S.

2017-10-01

We have studied disordering or atomic structure modification of ultra thin WO3 films under impact of high-energy ions with non-equilibrium and equilibrium charge incidence, by means of X-ray diffraction (XRD). WO3 films were prepared by thermal oxidation of W deposited on MgO substrate. Film thickness obtained by Rutherford backscattering spectrometry (RBS) is as low as 2 nm. Smoothness of film surface was observed by atomic force microscopy. It is found that the ratio of XRD intensity degradation per 90 MeV Ni+10 ion (the incident charge is lower than the equilibrium charge) to that per 90 MeV Ni ion with the equilibrium charge depends on the film thickness. Also, film thickness dependence is observed for 100 MeV Xe+14. By comparison of the experimental result with a simple model calculation based on the assumption that the mean charge of ions along the depth follows a saturation curve with power-law approximation to the charge dependent electronic stopping power, the characteristic length attaining the equilibrium charge is obtained to be ∼7 nm for 90 MeV Ni+10 ion incidence or the electron loss cross section of ∼1016 cm2, demonstrating that disordering of ultra WO3 films has been observed and a fundamental quantity can be derived through material modification.

High to ultra-high power electrical energy storage.

PubMed

Sherrill, Stefanie A; Banerjee, Parag; Rubloff, Gary W; Lee, Sang Bok

2011-12-14

High power electrical energy storage systems are becoming critical devices for advanced energy storage technology. This is true in part due to their high rate capabilities and moderate energy densities which allow them to capture power efficiently from evanescent, renewable energy sources. High power systems include both electrochemical capacitors and electrostatic capacitors. These devices have fast charging and discharging rates, supplying energy within seconds or less. Recent research has focused on increasing power and energy density of the devices using advanced materials and novel architectural design. An increase in understanding of structure-property relationships in nanomaterials and interfaces and the ability to control nanostructures precisely has led to an immense improvement in the performance characteristics of these devices. In this review, we discuss the recent advances for both electrochemical and electrostatic capacitors as high power electrical energy storage systems, and propose directions and challenges for the future. We asses the opportunities in nanostructure-based high power electrical energy storage devices and include electrochemical and electrostatic capacitors for their potential to open the door to a new regime of power energy.

Simulation of the Acoustic Pulse Expected from the Interaction of Ultra-High Energy Neutrinos and Seawater

DTIC Science & Technology

2006-03-01

the diameter. This equation is given by Sulak et. al. [1979] as: Eq 3 2 2 sin 8 o p EK cP C r d x ≅ x ’ Where sinLx π θ λ ⎛ ⎞= ⎜ ⎟ ⎝ ⎠ , L is...and others, "Sensitivity of an Underwater Acoustic Array to Ultra-High Energy Neutrinos", Astroparticle Physics, n.17, 2002. Sulak , L., Armstrong

Ultra-high-energy cosmic rays from low-luminosity active galactic nuclei

NASA Astrophysics Data System (ADS)

Duţan, Ioana; Caramete, Laurenţiu I.

2015-03-01

We investigate the production of ultra-high-energy cosmic ray (UHECR) in relativistic jets from low-luminosity active galactic nuclei (LLAGN). We start by proposing a model for the UHECR contribution from the black holes (BHs) in LLAGN, which present a jet power Pj ⩽1046 erg s-1. This is in contrast to the opinion that only high-luminosity AGN can accelerate particles to energies ⩾ 50 EeV. We rewrite the equations which describe the synchrotron self-absorbed emission of a non-thermal particle distribution to obtain the observed radio flux density from sources with a flat-spectrum core and its relationship to the jet power. We found that the UHECR flux is dependent on the observed radio flux density, the distance to the AGN, and the BH mass, where the particle acceleration regions can be sustained by the magnetic energy extraction from the BH at the center of the AGN. We use a complete sample of 29 radio sources with a total flux density at 5 GHz greater than 0.5 Jy to make predictions for the maximum particle energy, luminosity, and flux of the UHECRs from nearby AGN. These predictions are then used in a semi-analytical code developed in Mathematica (SAM code) as inputs for the Monte-Carlo simulations to obtain the distribution of the arrival direction at the Earth and the energy spectrum of the UHECRs, taking into account their deflection in the intergalactic magnetic fields. For comparison, we also use the CRPropa code with the same initial conditions as for the SAM code. Importantly, to calculate the energy spectrum we also include the weighting of the UHECR flux per each UHECR source. Next, we compare the energy spectrum of the UHECRs with that obtained by the Pierre Auger Observatory.

Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.

PubMed

Nobuhara, Chloe K; DeVos, Sarah L; Commins, Caitlin; Wegmann, Susanne; Moore, Benjamin D; Roe, Allyson D; Costantino, Isabel; Frosch, Matthew P; Pitstick, Rose; Carlson, George A; Hock, Christoph; Nitsch, Roger M; Montrasio, Fabio; Grimm, Jan; Cheung, Anne E; Dunah, Anthone W; Wittmann, Marion; Bussiere, Thierry; Weinreb, Paul H; Hyman, Bradley T; Takeda, Shuko

2017-06-01

The clinical progression of Alzheimer disease (AD) is associated with the accumulation of tau neurofibrillary tangles, which may spread throughout the cortex by interneuronal tau transfer. If so, targeting extracellular tau species may slow the spreading of tau pathology and possibly cognitive decline. To identify suitable target epitopes, we tested the effects of a panel of tau antibodies on neuronal uptake and aggregation in vitro. Immunodepletion was performed on brain extract from tau-transgenic mice and postmortem AD brain and added to a sensitive fluorescence resonance energy transfer-based tau uptake assay to assess blocking efficacy. The antibodies reduced tau uptake in an epitope-dependent manner: N-terminal (Tau13) and middomain (6C5 and HT7) antibodies successfully prevented uptake of tau species, whereas the distal C-terminal-specific antibody (Tau46) had little effect. Phosphorylation-dependent (40E8 and p396) and C-terminal half (4E4) tau antibodies also reduced tau uptake despite removing less total tau by immunodepletion, suggesting specific interactions with species involved in uptake. Among the seven antibodies evaluated, 6C5 most efficiently blocked uptake and subsequent aggregation. More important, 6C5 also blocked neuron-to-neuron spreading of tau in a unique three-chamber microfluidic device. Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Design and Performance Tests of Ultra-Compact Calorimeters for High Energy Astrophysics

NASA Technical Reports Server (NTRS)

Salgado, Carlos W.

2003-01-01

This R&D project had two goals: a) the study of general-application ultra-compact calorimetry technologies for use in High Energy Astrophysics and, b) contribute to the design of an efficient calorimeter for the ACCESS mission. The direct measurement of galactic cosmic ray fluxes is performed from space or from balloon-borne detectors. Detectors used in those studies are limited in size and, specially, in weight. Since galactic cosmic ray fluxes are very small, detectors with high geometrical acceptances and long exposures are usually required for collecting enough statistics. We have studied calorimeter techniques that could produce large geometrical acceptance per unit of mass (G/w) and that may be used to study galactic cosmic rays at intermediate energies (knee energies).-The most important asset for detection of primary cosmic rays at and about the knee is large acceptance. To construct a large acceptance calorimeter (this term is used here in its most general accepted meaning of calorimeter as a device to measure particle energies ) the detector needs to be verv liaht or verv shallow . We studied two possible technologies to built compact calorimeters: the use of lead-tungstate crystals (PWO) and the use of sampling calorimetry using scintillating fibers embedded in a matrix of powder tungsten. For a very light detector, we considered the possibility of using Optical Transition Radiation (OTR) to measure the energy (and perhaps also direction and identity) of VHE cosmic rays.

Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption

PubMed Central

Jones, Emmalee M.; Dubey, Manish; Camp, Phillip J.; Vernon, Briana C.; Biernat, Jacek; Mandelkow, Eckhard; Majewski, Jaroslaw; Chi, Eva Y.

2012-01-01

The misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that lipid membrane can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology. This prompted our investigation to assess tau's propensity to interact with membranes and to elucidate the mutually disruptive structural perturbations the interactions induce in both tau and the membrane. We show that although highly charged and soluble, the full-length tau (hTau40) is also highly surface active, selectively inserts into anionic DMPG lipid monolayers and induces membrane morphological changes. To resolve molecular-scale structural details of hTau40 associated with lipid membranes, X-ray and neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40's presence underneath a DMPG monolayer and penetration into the lipid headgroups and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40 insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid membrane interfaces induce the disordered hTau40 to partially adopt a more compact conformation with density similar to that of a folded protein. Neutron reflectivity shows that tau completely disrupts supported DMPG bilayers while leaving the neutral DPPC bilayer intact. Our results show that hTau40's strong interaction with anionic lipids induces tau structural compaction and membrane disruption, suggesting possible membrane-based mechanisms of tau aggregation and toxicity in neurodegenerative diseases. PMID:22401494

Observations of potential ultra high energy gamma-ray sources above 10(15) eV

NASA Technical Reports Server (NTRS)

Lambert, A.; Lloyd-Evans, J.; Perrett, J. C.; Watson, A. A.; West, A. A.

1985-01-01

The Haverah Park 50 m water-Cerenkov array has been used to examine a number of periodic sources for ultra high energy gamma-ray emission above 10 to the 15th power eV. The data, recorded between 1 Jan. 1979 and 31 Dec. 1984, feature a modest angular resolution of approx 3 deg with millisecond arrival time resolution post 1982. The sources investigated include the Crab pulsar, Her X-1, Au0115 + 63 and Geminga. All objects have been detected by workers in the TeV region, with varying degrees of confidence.

Spheromaks and how plasmas may explain the ultra high energy cosmic ray mystery

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

Fowler, T. Kenneth; Li, Hui

In recent papers, we show how accretion disks around massive black holes could act as dynamos producing magnetic jets similar to the jets that create spheromaks in the laboratory. In this paper, we discuss how these magnetic astrophysical jets might naturally produce runaway ion beams accelerated tomore » $$10^{20}$$ eV or more, finally ejected as ultra high energy cosmic rays (UHECRs) long regarded as one of the mysteries of astrophysics. The acceleration is mainly due to the drift cyclotron loss cone kinetic instability known from plasma research. Finally, experiments and simulations are suggested to verify the acceleration process.« less

Spheromaks and how plasmas may explain the ultra high energy cosmic ray mystery

DOE PAGES

Fowler, T. Kenneth; Li, Hui

2016-10-10

In recent papers, we show how accretion disks around massive black holes could act as dynamos producing magnetic jets similar to the jets that create spheromaks in the laboratory. In this paper, we discuss how these magnetic astrophysical jets might naturally produce runaway ion beams accelerated tomore » $$10^{20}$$ eV or more, finally ejected as ultra high energy cosmic rays (UHECRs) long regarded as one of the mysteries of astrophysics. The acceleration is mainly due to the drift cyclotron loss cone kinetic instability known from plasma research. Finally, experiments and simulations are suggested to verify the acceleration process.« less

Amyloid Beta and Tau as Alzheimer's Disease Blood Biomarkers: Promise From New Technologies.

PubMed

Lue, Lih-Fen; Guerra, Andre; Walker, Douglas G

2017-07-01

The utility of the levels of amyloid beta (Aβ) peptide and tau in blood for diagnosis, drug development, and assessment of clinical trials for Alzheimer's disease (AD) has not been established. The lack of availability of ultra-sensitive assays is one critical issue that has impeded progress. The levels of Aβ species and tau in plasma and serum are much lower than levels in cerebrospinal fluid. Furthermore, plasma or serum contain high levels of assay-interfering factors, resulting in difficulties in the commonly used singulex or multiplex ELISA platforms. In this review, we focus on two modern immune-complex-based technologies that show promise to advance this field. These innovative technologies are immunomagnetic reduction technology and single molecule array technology. We describe the technologies and discuss the published studies using these technologies. Currently, the potential of utilizing these technologies to advance Aβ and tau as blood-based biomarkers for AD requires further validation using already collected large sets of samples, as well as new cohorts and population-based longitudinal studies.

Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy.

PubMed

Congdon, Erin E; Lin, Yan; Rajamohamedsait, Hameetha B; Shamir, Dov B; Krishnaswamy, Senthilkumar; Rajamohamedsait, Wajitha J; Rasool, Suhail; Gonzalez, Veronica; Levenga, Josien; Gu, Jiaping; Hoeffer, Charles; Sigurdsson, Einar M

2016-08-30

A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological tau aggregates with high affinity would have the ideal therapeutic properties. Tau antibodies 4E6 and 6B2, raised against the same epitope region but of varying specificity and affinity, were tested for acutely improving cognition and reducing tau pathology in transgenic tauopathy mice and neuronal cultures. Surprisingly, we here show that one antibody, 4E6, which has low affinity for most forms of tau acutely improved cognition and reduced soluble phospho-tau, whereas another antibody, 6B2, which has high affinity for various tau species was ineffective. Concurrently, we confirmed and clarified these efficacy differences in an ex vivo model of tauopathy. Alzheimer's paired helical filaments (PHF) were toxic to the neurons and increased tau levels in remaining neurons. Both toxicity and tau seeding were prevented by 4E6 but not by 6B2. Furthermore, 4E6 reduced PHF spreading between neurons. Interestingly, 4E6's efficacy relates to its high affinity binding to solubilized PHF, whereas the ineffective 6B2 binds mainly to aggregated PHF. Blocking 4E6's uptake into neurons prevented its protective effects if the antibody was administered after PHF had been internalized. When 4E6 and PHF were administered at the same time, the antibody was protective extracellularly. Overall, these findings indicate that high antibody affinity for solubilized PHF predicts efficacy, and that acute antibody-mediated improvement in cognition relates to clearance of soluble phospho-tau. Importantly, both intra- and extracellular clearance pathways are in play. Together, these results have major implications for understanding the pathogenesis of tauopathies and for development of immunotherapies.

Measurement of the $$\\mathrm{Z}\\gamma^{*} \\to \\tau\\tau$$ cross section in pp collisions at $$\\sqrt{s} = $$ 13 TeV and validation of $$\\tau$$ lepton analysis techniques

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

Sirunyan, Albert M; et al.

A measurement is presented of themore » $$\\mathrm{Z}/\\gamma^{*} \\to \\tau\\tau$$ cross section in pp collisions at $$\\sqrt{s} = $$ 13 TeV, using data recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 2.3 fb$$^{-1}$$. The product of the inclusive cross section and branching fraction is measured to be $$\\sigma(\\mathrm{pp} \\to \\mathrm{Z}/\\gamma^{*}\\text{+X}) \\, \\mathcal{B}(\\mathrm{Z}/\\gamma^{*} \\to \\tau\\tau) = $$ 1848 $$\\pm$$ 12 (stat) $$\\pm$$ 67 (syst+lumi) pb, in agreement with the standard model expectation, computed at next-to-next-to-leading order accuracy in perturbative quantum chromodynamics. The measurement is used to validate new analysis techniques relevant for future measurements of $$\\tau$$ lepton production. The measurement also provides the reconstruction efficiency and energy scale for $$\\tau$$ decays to hadrons+$$\

Electric Field Strength Of Coherent Radio Emission In Rock Salt Concerning Ultra High-Energy Neutrino Detection

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

Watanabe, Y.; Chiba, M.; Yasuda, O.

2006-07-12

Detection possibility of ultra high-energy (UHE) neutrino (E >1015 eV) in natural huge rock salt formation has been studied. Collision between the UHE neutrino and the rock salt produces electromagnetic (EM) shower. Charge difference (excess electrons) between electrons and positrons in EM shower radiates radio wave coherently (Askar'yan effect). Angular distribution and frequency spectrum of electric field strength of radio wave radiated from 3-dimensional EM shower in rock salt are presented.

A strategy to unveil transient sources of ultra-high-energy cosmic rays

NASA Astrophysics Data System (ADS)

Takami, Hajime

2013-06-01

Transient generation of ultra-high-energy cosmic rays (UHECRs) has been motivated from promising candidates of UHECR sources such as gamma-ray bursts, flares of active galactic nuclei, and newly born neutron stars and magnetars. Here we propose a strategy to unveil transient sources of UHECRs from UHECR experiments. We demonstrate that the rate of UHECR bursts and/or flares is related to the apparent number density of UHECR sources, which is the number density estimated on the assumption of steady sources, and the time-profile spread of the bursts produced by cosmic magnetic fields. The apparent number density strongly depends on UHECR energies under a given rate of the bursts, which becomes observational evidence of transient sources. It is saturated at the number density of host galaxies of UHECR sources. We also derive constraints on the UHECR burst rate and/or energy budget of UHECRs per source as a function of the apparent source number density by using models of cosmic magnetic fields. In order to obtain a precise constraint of the UHECR burst rate, high event statistics above ˜ 1020 eV for evaluating the apparent source number density at the highest energies and better knowledge on cosmic magnetic fields by future observations and/or simulations to better estimate the time-profile spread of UHECR bursts are required. The estimated rate allows us to constrain transient UHECR sources by being compared with the occurrence rates of known energetic transient phenomena.

Ultra-high Temperature Emittance Measurements for Space and Missile Applications

NASA Technical Reports Server (NTRS)

Rogers, Jan; Crandall, David

2009-01-01

Advanced modeling and design efforts for many aerospace components require high temperature emittance data. Applications requiring emittance data include propulsion systems, radiators, aeroshells, heatshields/thermal protection systems, and leading edge surfaces. The objective of this work is to provide emittance data at ultra-high temperatures. MSFC has a new instrument for the measurement of emittance at ultra-high temperatures, the Ultra-High Temperature Emissometer System (Ultra-HITEMS). AZ Technology Inc. developed the instrument, designed to provide emittance measurements over the temperature range 700-3500K. The Ultra-HITEMS instrument measures the emittance of samples, heated by lasers, in vacuum, using a blackbody source and a Fourier Transform Spectrometer. Detectors in a Nicolet 6700 FT-IR spectrometer measure emittance over the spectral range of 0.4-25 microns. Emitted energy from the specimen and output from a Mikron M390S blackbody source at the same temperature with matched collection geometry are measured. Integrating emittance over the spectral range yields the total emittance. The ratio provides a direct measure of total hemispherical emittance. Samples are heated using lasers. Optical pyrometry provides temperature data. Optical filters prevent interference from the heating lasers. Data for Inconel 718 show excellent agreement with results from literature and ASTM 835. Measurements taken from levitated spherical specimens provide total hemispherical emittance data; measurements taken from flat specimens mounted in the chamber provide near-normal emittance data. Data from selected characterization studies will be presented. The Ultra-HITEMS technique could advance space and missile technologies by advancing the knowledge base and the technology readiness level for ultra-high temperature materials.

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer's disease-like tau pathology.

PubMed

Gratuze, Maud; Julien, Jacinthe; Petry, Franck R; Morin, Françoise; Planel, Emmanuel

2017-04-12

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients.

Dimer model for Tau proteins bound in microtubule bundles

NASA Astrophysics Data System (ADS)

Hall, Natalie; Kluber, Alexander; Hayre, N. Robert; Singh, Rajiv; Cox, Daniel

2013-03-01

The microtubule associated protein tau is important in nucleating and maintaining microtubule spacing and structure in neuronal axons. Modification of tau is implicated as a later stage process in Alzheimer's disease, but little is known about the structure of tau in microtubule bundles. We present preliminary work on a proposed model for tau dimers in microtubule bundles (dimers are the minimal units since there is one microtubule binding domain per tau). First, a model of tau monomer was created and its characteristics explored using implicit solvent molecular dynamics simulation. Multiple simulations yield a partially collapsed form with separate positively/negatively charged clumps, but which are a factor of two smaller than required by observed microtubule spacing. We argue that this will elongate in dimer form to lower electrostatic energy at a cost of entropic ``spring'' energy. We will present preliminary results on steered molecular dynamics runs on tau dimers to estimate the actual force constant. Supported by US NSF Grant DMR 1207624.

Ultra high vacuum broad band high power microwave window

DOEpatents

Nguyen-Tuong, V.; Dylla, H.F. III

1997-11-04

An improved high vacuum microwave window has been developed that utilizes high density polyethylene coated on two sides with SiOx, SiNx, or a combination of the two. The resultant low dielectric and low loss tangent window creates a low outgassing, low permeation seal through which broad band, high power microwave energy may be passed. No matching device is necessary and the sealing technique is simple. The features of the window are broad band transmission, ultra-high vacuum compatibility with a simple sealing technique, low voltage standing wave ratio, high power transmission and low cost. 5 figs.

Ultra high vacuum broad band high power microwave window

DOEpatents

Nguyen-Tuong, Viet; Dylla, III, Henry Frederick

1997-01-01

An improved high vacuum microwave window has been developed that utilizes high density polyethylene coated on two sides with SiOx, SiNx, or a combination of the two. The resultant low dielectric and low loss tangent window creates a low outgassing, low permeation seal through which broad band, high power microwave energy may be passed. No matching device is necessary and the sealing technique is simple. The features of the window are broad band transmission, ultra-high vacuum compatibility with a simple sealing technique, low voltage standing wave ratio, high power transmission and low cost.

Energy and flux measurements of ultra-high energy cosmic rays observed during the first ANITA flight

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

Schoorlemmer, H.; Belov, K.; Romero-Wolf, A.

The first flight of the Antarctic Impulsive Transient Antenna (ANITA) experiment recorded 16 radio signals that were emitted by cosmic-ray induced air showers. The dominant contribution to the radiation comes from the deflection of positrons and electrons in the geomagnetic field, which is beamed in the direction of motion of the air shower. For 14 of these events, this radiation is reflected from the ice and subsequently detected by the ANITA experiment at a flight altitude of ~36 km. In this paper, we estimate the energy of the 14 individual events and find that the mean energy of the cosmic-raymore » sample is 2.9 × 1018 eV, which is significantly lower than the previous estimate. By simulating the ANITA flight, we calculate its exposure for ultra-high energy cosmic rays. We estimate for the first time the cosmic-ray flux derived only from radio observations and find agreement with measurements performed at other observatories. In addition, we find that the ANITA data set is consistent with Monte Carlo simulations for the total number of observed events and with the properties of those events.« less

Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

PubMed Central

Takeda, Shuko; Wegmann, Susanne; Cho, Hansang; DeVos, Sarah L.; Commins, Caitlin; Roe, Allyson D.; Nicholls, Samantha B.; Carlson, George A.; Pitstick, Rose; Nobuhara, Chloe K.; Costantino, Isabel; Frosch, Matthew P.; Müller, Daniel J.; Irimia, Daniel; Hyman, Bradley T.

2015-01-01

Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. PMID:26458742

Industry-relevant magnetron sputtering and cathodic arc ultra-high vacuum deposition system for in situ x-ray diffraction studies of thin film growth using high energy synchrotron radiation.

PubMed

Schroeder, J L; Thomson, W; Howard, B; Schell, N; Näslund, L-Å; Rogström, L; Johansson-Jõesaar, M P; Ghafoor, N; Odén, M; Nothnagel, E; Shepard, A; Greer, J; Birch, J

2015-09-01

We present an industry-relevant, large-scale, ultra-high vacuum (UHV) magnetron sputtering and cathodic arc deposition system purposefully designed for time-resolved in situ thin film deposition/annealing studies using high-energy (>50 keV), high photon flux (>10(12) ph/s) synchrotron radiation. The high photon flux, combined with a fast-acquisition-time (<1 s) two-dimensional (2D) detector, permits time-resolved in situ structural analysis of thin film formation processes. The high-energy synchrotron-radiation based x-rays result in small scattering angles (<11°), allowing large areas of reciprocal space to be imaged with a 2D detector. The system has been designed for use on the 1-tonne, ultra-high load, high-resolution hexapod at the P07 High Energy Materials Science beamline at PETRA III at the Deutsches Elektronen-Synchrotron in Hamburg, Germany. The deposition system includes standard features of a typical UHV deposition system plus a range of special features suited for synchrotron radiation studies and industry-relevant processes. We openly encourage the materials research community to contact us for collaborative opportunities using this unique and versatile scientific instrument.

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer’s disease-like tau pathology

PubMed Central

Gratuze, Maud; Julien, Jacinthe; Petry, Franck R.; Morin, Françoise; Planel, Emmanuel

2017-01-01

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer’s disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients. PMID:28402338

Plasma Levels of Aβ42 and Tau Identified Probable Alzheimer's Dementia: Findings in Two Cohorts.

PubMed

Lue, Lih-Fen; Sabbagh, Marwan N; Chiu, Ming-Jang; Jing, Naomi; Snyder, Noelle L; Schmitz, Christopher; Guerra, Andre; Belden, Christine M; Chen, Ta-Fu; Yang, Che-Chuan; Yang, Shieh-Yueh; Walker, Douglas G; Chen, Kewei; Reiman, Eric M

2017-01-01

The utility of plasma amyloid beta (Aβ) and tau levels for the clinical diagnosis of Alzheimer's disease (AD) dementia has been controversial. The main objective of this study was to compare Aβ42 and tau levels measured by the ultra-sensitive immunomagnetic reduction (IMR) assays in plasma samples collected at the Banner Sun Health Institute (BSHRI) (United States) with those from the National Taiwan University Hospital (NTUH) (Taiwan). Significant increase in tau levels were detected in AD subjects from both cohorts, while Aβ42 levels were increased only in the NTUH cohort. A regression model incorporating age showed that tau levels identified probable ADs with 81 and 96% accuracy in the BSHRI and NTUH cohorts, respectively, while computed products of Aβ42 and tau increased the accuracy to 84% in the BSHRI cohorts. Using 382.68 (pg/ml) 2 as the cut-off value, the product achieved 92% accuracy in identifying AD in the combined cohorts. Overall findings support that plasma Aβ42 and tau assayed by IMR technology can be used to assist in the clinical diagnosis of AD.

Creation of ultra-high energy density matter using nanostructured targets

NASA Astrophysics Data System (ADS)

Tommasini, Riccardo; Park, J.; London, R.; Chen, H.; Hollinger, R. C.; Bargsten, C.; Shlyaptsev, V.; Capeluto, M.; Keiss, D.; Townsend, A.; Rocca, J. J.; Kaymak, V.; Pukhov, A.; Hill, M.

2015-11-01

Recent experiments have demonstrated that trapping of 60 femtosecond laser pulses of relativistic intensity deep within ordered nanowire arrays can create a new ultra-hot plasma regime. Here we report on the experiments at the Titan laser at the Lawrence Livermore National Laboratory that aim to scale these results by two orders of magnitude in laser energy. Preliminary analysis of the Titan results show that sub-picosecond laser irradiation of vertically aligned nanostructures of Au, Ag and Ni produces an increase of a factor greater than 1.6 in the suprathermal electron temperatures and an increase by a factor of 3 in the conversion efficiency into continuum x-rays, both with respect to flat targets of the same composition. Kα radiation from nanowire array targets also shows an increase between 3x and 5x over flat targets. The nanowire array targets reflected a 5x smaller fraction of the laser energy, indicating significantly larger absorption of the laser pulse. This work performed under the auspices of the U. S. Department of Energy by Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344, by the Office of Fusion Energy Sciences, U.S Department of Energy, and by the Defense Threat Reduction Agency grant HDTRA-1-10-1-0079.

Measurement of the absolute branching fraction of Ds+ --> tau+ nutau decay.

PubMed

Ecklund, K M; Love, W; Savinov, V; Lopez, A; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Rademacker, J; Asner, D M; Edwards, K W; Naik, P; Reed, J; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G

2008-04-25

Using a sample of tagged D(s)(+) decays collected near the D(s)(*+/-)D(s)(-/+) peak production energy in e(+)e(-) collisions with the CLEO-c detector, we study the leptonic decay D(s)(+)-->tau(+)nu(tau) via the decay channel tau(+)-->e(+)nu(e)nu(tau). We measure B(D(s)(+)-->tau(+)nu(tau))=(6.17+/-0.71+/-0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of D(s)(+)-->mu(+)nu(mu) and D(s)(+)-->tau(+)nu(tau) (via tau(+)-->pi(+)nu(tau)), we determine f(D(s))=(274+/-10+/-5) MeV.

Study of Small-Scale Anisotropy of Ultra-High-Energy Cosmic Rays Observed in Stereo by the High Resolution Fly's Eye Detector

NASA Astrophysics Data System (ADS)

Abbasi, R. U.; Abu-Zayyad, T.; Amann, J. F.; Archbold, G.; Atkins, R.; Bellido, J. A.; Belov, K.; Belz, J. W.; BenZvi, S.; Bergman, D. R.; Boyer, J. H.; Burt, G. W.; Cao, Z.; Clay, R. W.; Connolly, B. M.; Dawson, B. R.; Deng, W.; Fedorova, Y.; Findlay, J.; Finley, C. B.; Hanlon, W. F.; Hoffman, C. M.; Holzscheiter, M. H.; Hughes, G. A.; Hüntemeyer, P.; Jui, C. C. H.; Kim, K.; Kirn, M. A.; Knapp, B. C.; Loh, E. C.; Maestas, M. M.; Manago, N.; Mannel, E. J.; Marek, L. J.; Martens, K.; Matthews, J. A. J.; Matthews, J. N.; O'Neill, A.; Painter, C. A.; Perera, L.; Reil, K.; Riehle, R.; Roberts, M. D.; Sasaki, M.; Schnetzer, S. R.; Seman, M.; Simpson, K. M.; Sinnis, G.; Smith, J. D.; Snow, R.; Sokolsky, P.; Song, C.; Springer, R. W.; Stokes, B. T.; Thomas, J. R.; Thomas, S. B.; Thomson, G. B.; Tupa, D.; Westerhoff, S.; Wiencke, L. R.; Zech, A.; HIRES Collaboration

2004-08-01

The High Resolution Fly's Eye (HiRes) experiment is an air fluorescence detector which, operating in stereo mode, has a typical angular resolution of 0.6d and is sensitive to cosmic rays with energies above 1018 eV. The HiRes cosmic-ray detector is thus an excellent instrument for the study of the arrival directions of ultra-high-energy cosmic rays. We present the results of a search for anisotropies in the distribution of arrival directions on small scales (<5°) and at the highest energies (>1019 eV). The search is based on data recorded between 1999 December and 2004 January, with a total of 271 events above 1019 eV. No small-scale anisotropy is found, and the strongest clustering found in the HiRes stereo data is consistent at the 52% level with the null hypothesis of isotropically distributed arrival directions.

Increased Tau Phosphorylation and Tau Truncation, and Decreased Synaptophysin Levels in Mutant BRI2/Tau Transgenic Mice

PubMed Central

Garringer, Holly J.; Murrell, Jill; Sammeta, Neeraja; Gnezda, Anita; Ghetti, Bernardino; Vidal, Ruben

2013-01-01

Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease caused by a 10-nucleotide duplication-insertion in the BRI2 gene. FDD is clinically characterized by loss of vision, hearing impairment, cerebellar ataxia and dementia. The main neuropathologic findings in FDD are the deposition of Danish amyloid (ADan) and the presence of neurofibrillary tangles (NFTs). Here we investigated tau accumulation and truncation in double transgenic (Tg-FDD-Tau) mice generated by crossing transgenic mice expressing human Danish mutant BRI2 (Tg-FDD) with mice expressing human 4-repeat mutant Tau-P301S (Tg-Tau). Compared to Tg-Tau mice, we observed a significant enhancement of tau deposition in Tg-FDD-Tau mice. In addition, a significant increase in tau cleaved at aspartic acid (Asp) 421 was observed in Tg-FDD-Tau mice. Tg-FDD-Tau mice also showed a significant decrease in synaptophysin levels, occurring before widespread deposition of fibrillar ADan and tau can be observed. Thus, the presence of soluble ADan/mutant BRI2 can lead to significant changes in tau metabolism and synaptic dysfunction. Our data provide new in vivo insights into the pathogenesis of FDD and the pathogenic pathway(s) by which amyloidogenic peptides, regardless of their primary amino acid sequence, can cause neurodegeneration. PMID:23418567

Increased tau phosphorylation and tau truncation, and decreased synaptophysin levels in mutant BRI2/tau transgenic mice.

PubMed

Garringer, Holly J; Murrell, Jill; Sammeta, Neeraja; Gnezda, Anita; Ghetti, Bernardino; Vidal, Ruben

2013-01-01

Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease caused by a 10-nucleotide duplication-insertion in the BRI(2) gene. FDD is clinically characterized by loss of vision, hearing impairment, cerebellar ataxia and dementia. The main neuropathologic findings in FDD are the deposition of Danish amyloid (ADan) and the presence of neurofibrillary tangles (NFTs). Here we investigated tau accumulation and truncation in double transgenic (Tg-FDD-Tau) mice generated by crossing transgenic mice expressing human Danish mutant BRI(2) (Tg-FDD) with mice expressing human 4-repeat mutant Tau-P301S (Tg-Tau). Compared to Tg-Tau mice, we observed a significant enhancement of tau deposition in Tg-FDD-Tau mice. In addition, a significant increase in tau cleaved at aspartic acid (Asp) 421 was observed in Tg-FDD-Tau mice. Tg-FDD-Tau mice also showed a significant decrease in synaptophysin levels, occurring before widespread deposition of fibrillar ADan and tau can be observed. Thus, the presence of soluble ADan/mutant BRI(2) can lead to significant changes in tau metabolism and synaptic dysfunction. Our data provide new in vivo insights into the pathogenesis of FDD and the pathogenic pathway(s) by which amyloidogenic peptides, regardless of their primary amino acid sequence, can cause neurodegeneration.

Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation

PubMed Central

Cohen, Todd J.; Constance, Brian H.; Hwang, Andrew W.; James, Michael; Yuan, Chao-Xing

2016-01-01

Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer’s disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies. PMID:27383765

Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation.

PubMed

Cohen, Todd J; Constance, Brian H; Hwang, Andrew W; James, Michael; Yuan, Chao-Xing

2016-01-01

Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer's disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies.

The mass composition of ultra-high energy cosmic rays with the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Martraire, D.

2014-12-01

Ultra-high energy cosmic rays are the most energetic particles known in nature. The Pierre Auger Observatory was built to study these amazing particles to determine their origin. The study of their mass composition can help to constrain the models concerning their origins and their production mechanisms in the astrophysical sources. To this aim, several methods have been developed to infer the composition using the Auger surface detector array data. The main difficulty is to isolate the muonic component in the signal measured by the surface detector. We present the results of the composition parameters derived from the ground level component and compare them to the predictions for different nuclear masses of the primary particles and hadronic interaction models.

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.

PubMed

Paranjape, Smita R; Riley, Andrew P; Somoza, Amber D; Oakley, C Elizabeth; Wang, Clay C C; Prisinzano, Thomas E; Oakley, Berl R; Gamblin, T Chris

2015-05-20

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer's disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, and four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and number of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau's normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold.

Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau.

PubMed

Lasagna-Reeves, Cristian A; Castillo-Carranza, Diana L; Sengupta, Urmi; Guerrero-Munoz, Marcos J; Kiritoshi, Takaki; Neugebauer, Volker; Jackson, George R; Kayed, Rakez

2012-01-01

Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and tau pathology. We extracted pure populations of tau oligomers directly from the cerebral cortex of Alzheimer disease (AD) brain. These oligomers are potent inhibitors of long term potentiation (LTP) in hippocampal brain slices and disrupt memory in wild type mice. We observed for the first time that these authentic brain-derived tau oligomers propagate abnormal tau conformation of endogenous murine tau after prolonged incubation. The conformation and hydrophobicity of tau oligomers play a critical role in the initiation and spread of tau pathology in the naïve host in a manner reminiscent of sporadic AD.

Implications of the pseudo-Dirac scenario for ultra high energy neutrinos from GRBs

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

Esmaili, Arman; Farzan, Yasaman, E-mail: aesmaili@ifi.unicamp.br, E-mail: yasaman@theory.ipm.ac.ir

2012-12-01

The source of Ultra High Energy Cosmic Rays (UHECR) is still an unresolved mystery. Up until recently, sources of Gamma Ray Bursts (GRBs) had been considered as a suitable source for UHECR. Within the fireball model, the UHECR produced at GRBs should be accompanied with a neutrino flux detectable at the neutrino telescope such as IceCube. Recently, IceCube has set an upper bound on the neutrino flux accompanied by GRBs about 3.7 times below the prediction. We investigate whether this deficit can be explained by the oscillation of the active neutrinos to sterile neutrinos en route from the source tomore » the detectors within the pseudo-Dirac scenario. We then discuss the implication of this scenario for diffuse supernova relic neutrinos.« less

ON ULTRA-HIGH-ENERGY COSMIC RAYS AND THEIR RESULTANT GAMMA-RAYS

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

Gavish, Eyal; Eichler, David

2016-05-01

The Fermi Large Area Telescope collaboration has recently reported on 50 months of measurements of the isotropic extragalactic gamma-ray background (EGRB) spectrum between 100 MeV and 820 GeV. Ultra-high-energy cosmic ray (UHECR) protons interact with the cosmic microwave background photons and produce cascade photons of energies 10 MeV–1 TeV that contribute to the EGRB flux. We examine seven possible evolution models for UHECRs and find that UHECR sources that evolve as the star formation rate (SFR), medium low luminosity active galactic nuclei type-1 ( L = 10{sup 43.5} erg s{sup −1} in the [0.5–2] KeV band), and BL Lacertae objectsmore » (BL Lacs) are the most acceptable given the constraints imposed by the observed EGRB. Other possibilities produce too much secondary γ -radiation. In all cases, the decaying dark matter (DM) contribution improves the fit at high energy, but the contribution of still unresolved blazars, which would leave the smallest role for decaying DM, may yet provide an alternative improvement. The possibility that the entire EGRB can be fitted with resolvable but not-yet-resolved blazars, as recently claimed by Ajello et al., would leave little room in the EGRB to accommodate γ -rays from extragalactic UHECR production, even for many source evolution rates that would otherwise be acceptable. We find that under the assumption of UHECRs being mostly protons, there is not enough room for producing extragalactic UHECRs with active galactic nucleus, gamma-ray burst, or even SFR source evolution. Sources that evolve as BL Lacs, on the other hand, would produce much less secondary γ -radiation and would remain a viable source of UHECRs, provided that they dominate.« less

Search for ultrahigh-energy tau neutrinos with IceCube

NASA Astrophysics Data System (ADS)

Abbasi, R.; Abdou, Y.; Abu-Zayyad, T.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Altmann, D.; Andeen, K.; Auffenberg, J.; Bai, X.; Baker, M.; Barwick, S. W.; Baum, V.; Bay, R.; Beattie, K.; Beatty, J. J.; Bechet, S.; Becker, J. K.; Becker, K.-H.; Bell, M.; Benabderrahmane, M. L.; BenZvi, S.; Berdermann, J.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Bindig, D.; Bissok, M.; Blaufuss, E.; Blumenthal, J.; Boersma, D. J.; Bohm, C.; Bose, D.; Böser, S.; Botner, O.; Brayeur, L.; Brown, A. M.; Buitink, S.; Caballero-Mora, K. S.; Carson, M.; Casier, M.; Chirkin, D.; Christy, B.; Clevermann, F.; Cohen, S.; Cowen, D. F.; Cruz Silva, A. H.; D'Agostino, M. V.; Danninger, M.; Daughhetee, J.; Davis, J. C.; De Clercq, C.; Degner, T.; Descamps, F.; Desiati, P.; de Vries-Uiterweerd, G.; DeYoung, T.; Díaz-Vélez, J. C.; Dreyer, J.; Dumm, J. P.; Dunkman, M.; Eisch, J.; Ellsworth, R. W.; Engdegård, O.; Euler, S.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Fedynitch, A.; Feintzeig, J.; Feusels, T.; Filimonov, K.; Finley, C.; Fischer-Wasels, T.; Flis, S.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Gladstone, L.; Glüsenkamp, T.; Goldschmidt, A.; Goodman, J. A.; Góra, D.; Grant, D.; Groß, A.; Grullon, S.; Gurtner, M.; Ha, C.; Haj Ismail, A.; Hallgren, A.; Halzen, F.; Hanson, K.; Heereman, D.; Heimann, P.; Heinen, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hill, G. C.; Hoffman, K. D.; Hoffmann, B.; Homeier, A.; Hoshina, K.; Huelsnitz, W.; Hulth, P. O.; Hultqvist, K.; Hussain, S.; Ishihara, A.; Jacobi, E.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Kappes, A.; Karg, T.; Karle, A.; Kiryluk, J.; Kislat, F.; Klein, S. R.; Köhne, J.-H.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krasberg, M.; Kroll, G.; Kunnen, J.; Kurahashi, N.; Kuwabara, T.; Labare, M.; Laihem, K.; Landsman, H.; Larson, M. J.; Lauer, R.; Lünemann, J.; Madsen, J.; Maruyama, R.; Mase, K.; Matis, H. S.; Meagher, K.; Merck, M.; Mészáros, P.; Meures, T.; Miarecki, S.; Middell, E.; Milke, N.; Miller, J.; Montaruli, T.; Morse, R.; Movit, S. M.; Nahnhauer, R.; Nam, J. W.; Naumann, U.; Nowicki, S. C.; Nygren, D. R.; Odrowski, S.; Olivas, A.; Olivo, M.; O'Murchadha, A.; Panknin, S.; Paul, L.; Pérez de los Heros, C.; Pieloth, D.; Posselt, J.; Price, P. B.; Przybylski, G. T.; Rawlins, K.; Redl, P.; Resconi, E.; Rhode, W.; Ribordy, M.; Richman, M.; Riedel, B.; Rodrigues, J. P.; Rothmaier, F.; Rott, C.; Ruhe, T.; Rutledge, D.; Ruzybayev, B.; Ryckbosch, D.; Sander, H.-G.; Santander, M.; Sarkar, S.; Schatto, K.; Scheel, M.; Schmidt, T.; Schöneberg, S.; Schönwald, A.; Schukraft, A.; Schulte, L.; Schultes, A.; Schulz, O.; Schunck, M.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Smith, M. W. E.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Strahler, E. A.; Ström, R.; Stüer, M.; Sullivan, G. W.; Taavola, H.; Taboada, I.; Tamburro, A.; Ter-Antonyan, S.; Tilav, S.; Toale, P. A.; Toscano, S.; van Eijndhoven, N.; Van Overloop, A.; van Santen, J.; Vehring, M.; Voge, M.; Walck, C.; Waldenmaier, T.; Wallraff, M.; Walter, M.; Wasserman, R.; Weaver, Ch.; Wendt, C.; Westerhoff, S.; Whitehorn, N.; Wiebe, K.; Wiebusch, C. H.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Wolf, M.; Wood, T. R.; Woschnagg, K.; Xu, C.; Xu, D. L.; Xu, X. W.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zarzhitsky, P.; Zoll, M.

2012-07-01

The first dedicated search for ultrahigh-energy (UHE) tau neutrinos of astrophysical origin was performed using the IceCube detector in its 22-string configuration with an instrumented volume of roughly 0.25km3. The search also had sensitivity to UHE electron and muon neutrinos. After application of all selection criteria to approximately 200 live-days of data, we expect a background of 0.60±0.19(stat)(+0.56)/(-0.58)(syst) events and observe three events, which after inspection, emerge as being compatible with background but are kept in the final sample. Therefore, we set an upper limit on neutrinos of all flavors from UHE astrophysical sources at 90% C.L. of Eν2Φ90(νx)<16.3×10-8GeVcm-2sr-1s-1 over an estimated primary neutrino energy range of 340 TeV to 200 PeV.

Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

PubMed

Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

2017-01-01

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

Waste heat recovery with ultra high-speed turbomachinery

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

Vakkilainen, E.; Larjola, J.; Lindgren, O.

1984-08-01

A new ORC heat recovery system which converts waste heat to electricity has been developed in Lappeenranta University of Technology with support from Department of Energy in Finnish Ministry of Trade and Industry. Use of ultra high-speed turbomachinery (10 000 rpm - 200 000 rpm) promises lower unit costs, higher efficiencies and fast amortization rate, 2,4 - 3,0 years.

Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells.

PubMed

Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Zhou, Qi-Da; Xu, Lin; Zhang, Zhi-Jun

2015-06-01

To investigate the effect of escitalopram (a widely used and highly efficacious antidepressant from the SSRI class) on tau hyperphosphorylation, HEK293/tau441 cells were pretreated with 4 μM of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 μM) for 22 h. We measured the phosphorylation level of tau by Western blotting. It was shown that escitalopram could protect tau from hyperphosphorylation induced by pharmacological activation of protein kinase A (PKA) at a dose of 20, 40, and 80 μM in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3β (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3β and Akt. Unexpectedly, 5-hydroxytryptamine 1A receptor (5-HT1A) agonist 8-OH-DPAT did not decrease forskolin-induced tau hyperphosphorylation. Our results suggest that escitalopram can ameliorate forskolin-induced tau hyperphosphorylation, which is not through the typical 5-HT1A pathway, and Akt/GSK-3β signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.

The MIDAS telescope for microwave detection of ultra-high energy cosmic rays

NASA Astrophysics Data System (ADS)

Alvarez-Muñiz, J.; Amaral Soares, E.; Berlin, A.; Bogdan, M.; Boháčová, M.; Bonifazi, C.; Carvalho, W. R.; de Mello Neto, J. R. T.; Facal San Luis, P.; Genat, J. F.; Hollon, N.; Mills, E.; Monasor, M.; Privitera, P.; Ramos de Castro, A.; Reyes, L. C.; Richardson, M.; Rouille d'Orfeuil, B.; Santos, E. M.; Wayne, S.; Williams, C.; Zas, E.; Zhou, J.

2013-08-01

We present the design, implementation and data taking performance of the MIcrowave Detection of Air Showers (MIDAS) experiment, a large field of view imaging telescope designed to detect microwave radiation from extensive air showers induced by ultra-high energy cosmic rays. This novel technique may bring a tenfold increase in detector duty cycle when compared to the standard fluorescence technique based on detection of ultraviolet photons. The MIDAS telescope consists of a 4.5 m diameter dish with a 53-pixel receiver camera, instrumented with feed horns operating in the commercial extended C-Band (3.4-4.2 GHz). A self-trigger capability is implemented in the digital electronics. The main objectives of this first prototype of the MIDAS telescope - to validate the telescope design, and to demonstrate a large detector duty cycle - were successfully accomplished in a dedicated data taking run at the University of Chicago campus prior to installation at the Pierre Auger Observatory.

Effects of antibodies to phosphorylated and non-phosphorylated tau on in vitro tau phosphorylation at Serine-199: Preliminary report.

PubMed

Loeffler, David A; Smith, Lynnae M; Klaver, Andrea C; Martić, Sanela

2015-07-01

Phosphorylation of multiple amino acids on tau protein ("hyperphosphorylation") is required for the development of tau pathology in Alzheimer's disease. Administration of anti-tau antibodies to transgenic "tauopathy mice" has been shown to reduce their tau pathology but the mechanisms responsible are unclear. To examine the effects of anti-tau antibodies on tau phosphorylation, we used western blots to study the effects of three antibodies to phosphorylated tau (pTau), namely anti-pTau S199, T231, and S396, and three antibodies to non-phosphorylated tau on in vitro phosphorylation of recombinant human tau-441 at S199. Inclusion of an anti-pTau T231 antibody in the phosphorylation reaction reduced the intensity of monomeric pTau S199 in western blots of denaturing gels, but the other antibodies had no apparent effects on this process. Surprisingly, including all three anti-phospho-tau antibodies in the reaction did not reduce the intensity of the monomer band, possibly due to steric hindrance between the antibodies. These preliminary findings suggest that anti-tau antibodies may have minimal direct effects on tau phosphorylation. Limitations of using western blots to examine the effects of anti-tau antibodies on this process were found to include between-experiment variability in pTau band densities and poor resolution of high molecular weight pTau oligomers. The presence of bands representing immunoglobulins as well as pTau may also complicate interpretation of the western blots. Further studies are indicated to examine the effects of anti-pTau antibodies on phosphorylation of other tau amino acids in addition to S199. Copyright © 2015 Elsevier Inc. All rights reserved.

CRPropa 3—a public astrophysical simulation framework for propagating extraterrestrial ultra-high energy particles

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

Batista, Rafael Alves; Dundovic, Andrej; Sigl, Guenter

2016-05-01

We present the simulation framework CRPropa version 3 designed for efficient development of astrophysical predictions for ultra-high energy particles. Users can assemble modules of the most relevant propagation effects in galactic and extragalactic space, include their own physics modules with new features, and receive on output primary and secondary cosmic messengers including nuclei, neutrinos and photons. In extension to the propagation physics contained in a previous CRPropa version, the new version facilitates high-performance computing and comprises new physical features such as an interface for galactic propagation using lensing techniques, an improved photonuclear interaction calculation, and propagation in time dependent environmentsmore » to take into account cosmic evolution effects in anisotropy studies and variable sources. First applications using highlighted features are presented as well.« less

Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

PubMed Central

Yanamandra, Kiran; Patel, Tirth K.; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D.; Boxer, Adam L.; Miller, Bruce L.; Kerwin, Diana R.; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J.; Verghese, Philip B.; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S.; Hu, Yan; Holtzman, David M.

2017-01-01

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. PMID:28424326

The energy spectrum of ultra-high-energy cosmic rays measured by the Telescope Array FADC fluorescence detectors in monocular mode

NASA Astrophysics Data System (ADS)

Abu-Zayyad, T.; Aida, R.; Allen, M.; Anderson, R.; Azuma, R.; Barcikowski, E.; Belz, J. W.; Bergman, D. R.; Blake, S. A.; Cady, R.; Cheon, B. G.; Chiba, J.; Chikawa, M.; Cho, E. J.; Cho, W. R.; Fujii, H.; Fujii, T.; Fukuda, T.; Fukushima, M.; Hanlon, W.; Hayashi, K.; Hayashi, Y.; Hayashida, N.; Hibino, K.; Hiyama, K.; Honda, K.; Iguchi, T.; Ikeda, D.; Ikuta, K.; Inoue, N.; Ishii, T.; Ishimori, R.; Ito, H.; Ivanov, D.; Iwamoto, S.; Jui, C. C. H.; Kadota, K.; Kakimoto, F.; Kalashev, O.; Kanbe, T.; Kasahara, K.; Kawai, H.; Kawakami, S.; Kawana, S.; Kido, E.; Kim, H. B.; Kim, H. K.; Kim, J. H.; Kim, J. H.; Kitamoto, K.; Kitamura, S.; Kitamura, Y.; Kobayashi, K.; Kobayashi, Y.; Kondo, Y.; Kuramoto, K.; Kuzmin, V.; Kwon, Y. J.; Lan, J.; Lim, S. I.; Lundquist, J. P.; Machida, S.; Martens, K.; Matsuda, T.; Matsuura, T.; Matsuyama, T.; Matthews, J. N.; Myers, I.; Minamino, M.; Miyata, K.; Murano, Y.; Nagataki, S.; Nakamura, T.; Nam, S. W.; Nonaka, T.; Ogio, S.; Ogura, J.; Ohnishi, M.; Ohoka, H.; Oki, K.; Oku, D.; Okuda, T.; Ono, M.; Oshima, A.; Ozawa, S.; Park, I. H.; Pshirkov, M. S.; Rodriguez, D. C.; Roh, S. Y.; Rubtsov, G.; Ryu, D.; Sagawa, H.; Sakurai, N.; Sampson, A. L.; Scott, L. M.; Shah, P. D.; Shibata, F.; Shibata, T.; Shimodaira, H.; Shin, B. K.; Shin, J. I.; Shirahama, T.; Smith, J. D.; Sokolsky, P.; Sonley, T. J.; Springer, R. W.; Stokes, B. T.; Stratton, S. R.; Stroman, T. A.; Suzuki, S.; Takahashi, Y.; Takeda, M.; Taketa, A.; Takita, M.; Tameda, Y.; Tanaka, H.; Tanaka, K.; Tanaka, M.; Thomas, S. B.; Thomson, G. B.; Tinyakov, P.; Tkachev, I.; Tokuno, H.; Tomida, T.; Troitsky, S.; Tsunesada, Y.; Tsutsumi, K.; Tsuyuguchi, Y.; Uchihori, Y.; Udo, S.; Ukai, H.; Vasiloff, G.; Wada, Y.; Wong, T.; Yamakawa, Y.; Yamane, R.; Yamaoka, H.; Yamazaki, K.; Yang, J.; Yoneda, Y.; Yoshida, S.; Yoshii, H.; Zollinger, R.; Zundel, Z.

2013-08-01

We present a measurement of the energy spectrum of ultra-high-energy cosmic rays performed by the Telescope Array experiment using monocular observations from its two new FADC-based fluorescence detectors. After a short description of the experiment, we describe the data analysis and event reconstruction procedures. Since the aperture of the experiment must be calculated by Monte Carlo simulation, we describe this calculation and the comparisons of simulated and real data used to verify the validity of the aperture calculation. Finally, we present the energy spectrum calculated from the merged monocular data sets of the two FADC-based detectors, and also the combination of this merged spectrum with an independent, previously published monocular spectrum measurement performed by Telescope Array's third fluorescence detector [T. Abu-Zayyad et al., The energy spectrum of Telescope Array's middle drum detector and the direct comparison to the high resolution fly's eye experiment, Astroparticle Physics 39 (2012) 109-119, http://dx.doi.org/10.1016/j.astropartphys.2012.05.012, Available from: ]. This combined spectrum corroborates the recently published Telescope Array surface detector spectrum [T. Abu-Zayyad, et al., The cosmic-ray energy spectrum observed with the surface detector of the Telescope Array experiment, ApJ 768 (2013) L1, http://dx.doi.org/10.1088/2041-8205/768/1/L1, Available from: ] with independent systematic uncertainties.

Chemical Abundance Measurements of Ultra-Faint Dwarf Galaxies Discovered by the Dark Energy Survey

NASA Astrophysics Data System (ADS)

Nagasawa, Daniel; Marshall, Jennifer L.; Simon, Joshua D.; Hansen, Terese; Li, Ting; Bernstein, Rebecca; Balbinot, Eduardo; Drlica-Wagner, Alex; Pace, Andrew; Strigari, Louis; Pellegrino, Craig; DePoy, Darren L.; Suntzeff, Nicholas; Bechtol, Keith; Dark Energy Suvey

2018-01-01

We present chemical abundance analysis results derived from high-resolution spectroscopy of ultra-faint dwarfs discovered by the Dark Energy Survey. Ultra-faint dwarf galaxies preserve a fossil record of the chemical abundance patterns imprinted by the first stars in the Universe. High-resolution spectroscopic observations of member stars in several recently discovered Milky Way satellites reveal a range of abundance patterns among ultra-faint dwarfs suggesting that star formation processes in the early Universe were quite diverse. The chemical content provides a glimpse not only of the varied nucleosynthetic processes and chemical history of the dwarfs themselves, but also the environment in which they were formed. We present the chemical abundance analysis of these objects and discuss possible explanations for the observed abundance patterns.

Implications of a electroweak triplet scalar leptoquark on the ultra-high energy neutrino events at IceCube

NASA Astrophysics Data System (ADS)

Mileo, Nicolas; de la Puente, Alejandro; Szynkman, Alejandro

2016-11-01

We study the production of scalar leptoquarks at IceCube, in particular, a particle transforming as a triplet under the weak interaction. The existence of electroweak-triplet scalars is highly motivated by models of grand unification and also within radiative seesaw models for neutrino mass generation. In our framework, we extend the Standard Model by a single colored electroweak-triplet scalar leptoquark and analyze its implications on the excess of ultra-high energy neutrino events observed by the IceCube collaboration. We consider only couplings between the leptoquark to first generation of quarks and first and second generations of leptons, and carry out a statistical analysis to determine the parameters that best describe the IceCube data as well as set 95% CL upper bounds. We analyze whether this study is still consistent with most up-to-date LHC data and various low energy observables.

Closing the tau loop: the missing tau mutation

PubMed Central

McCarthy, Allan; Lonergan, Roisin; Olszewska, Diana A.; O’Dowd, Sean; Cummins, Gemma; Magennis, Brian; Fallon, Emer M.; Pender, Niall; Huey, Edward D.; Cosentino, Stephanie; O’Rourke, Killian; Kelly, Brendan D.; O’Connell, Martin; Delon, Isabelle; Farrell, Michael; Spillantini, Maria Grazia; Rowland, Lewis P.; Fahn, Stanley; Craig, Peter; Hutton, Michael

2015-01-01

Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5’ splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the ‘missing’ +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the ‘stem’ when the

Ultra High Bypass Integrated System Test

NASA Image and Video Library

2015-09-14

NASA’s Environmentally Responsible Aviation Project, in collaboration with the Federal Aviation Administration (FAA) and Pratt & Whitney, completed testing of an Ultra High Bypass Ratio Turbofan Model in the 9’ x 15’ Low Speed Wind Tunnel at NASA Glenn Research Center. The fan model is representative of the next generation of efficient and quiet Ultra High Bypass Ratio Turbofan Engine designs.

Ultra-low switching energy and scaling in electric-field-controlled nanoscale magnetic tunnel junctions with high resistance-area product

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

Grezes, C.; Alzate, J. G.; Cai, X.

2016-01-04

We report electric-field-induced switching with write energies down to 6 fJ/bit for switching times of 0.5 ns, in nanoscale perpendicular magnetic tunnel junctions (MTJs) with high resistance-area product and diameters down to 50 nm. The ultra-low switching energy is made possible by a thick MgO barrier that ensures negligible spin-transfer torque contributions, along with a reduction of the Ohmic dissipation. We find that the switching voltage and time are insensitive to the junction diameter for high-resistance MTJs, a result accounted for by a macrospin model of purely voltage-induced switching. The measured performance enables integration with same-size CMOS transistors in compact memorymore » and logic integrated circuits.« less

The influence of the observatory latitude on the study of ultra high energy cosmic rays

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

Anjos, Rita C. dos; De Souza, Vitor; De Almeida, Rogerio M.

2017-07-01

Recent precision measurements of the Ultra High Energy Cosmic Rays (UHECR) arrival directions, spectrum and parameters related to the mass of the primary particle have been done by the HiRes, Pierre Auger and Telescope Array (TA) Observatories. In this paper, distributions of arrival directions of events in the nearby Universe are assumed to correlate with sources in the 2MASS Redshift Survey (2MRS), IRAS 1.2 Jy Survey, Palermo Swift-BAT and Swift-BAT catalogs, and the effect of the latitude of the observatory on the measurement of the energy spectrum and on the capability of measuring anisotropy is studied. The differences between givenmore » latitudes on the northern and southern hemispheres are quantified. It is shown that the latitude of the observatory: a) has an influence on the total flux measured and b) imposes an important limitation on the capability of measuring an anisotropic sky.« less

Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.

PubMed

d'Abramo, Cristina; Acker, Christopher M; Schachter, Joel B; Terracina, Giuseppe; Wang, Xiaohai; Forest, Stefanie K; Davies, Peter

2016-01-01

In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

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

Higginson, Drew Pitney

2013-01-01

The cone-guided fast ignition approach to Inertial Con nement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets whenmore » intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the rst time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of K x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an e ective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser at

Tau Phosphorylation Pathway Genes and Cerebrospinal Fluid Tau Levels in Alzheimer’s Disease

PubMed Central

Bekris, Lynn M.; Millard, Steve; Lutz, Franziska; Li, Gail; Galasko, Doug R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby W.; Yu, Chang-En; Peskind, Elaine R.

2013-01-01

Alzheimer’s disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid β peptide (Aβ), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5′ and 3′ regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner. PMID:22927204

Wide band cryogenic ultra-high vacuum microwave absorber

DOEpatents

Campisi, I.E.

1992-05-12

An absorber waveguide assembly for absorbing higher order modes of microwave energy under cryogenic ultra-high vacuum conditions, that absorbs wide-band multi-mode energy. The absorber is of a special triangular shape, made from flat tiles of silicon carbide and aluminum nitride. The leading sharp end of the absorber is located in a corner of the waveguide and tapers to a larger cross-sectional area whose center is located approximately in the center of the wave guide. The absorber is relatively short, being of less height than the maximum width of the waveguide. 11 figs.

Wide band cryogenic ultra-high vacuum microwave absorber

DOEpatents

Campisi, Isidoro E.

1992-01-01

An absorber wave guide assembly for absorbing higher order modes of microwave energy under cryogenic ultra-high vacuum conditions, that absorbs wide-band multi-mode energy. The absorber is of a special triangular shape, made from flat tiles of silicon carbide and aluminum nitride. The leading sharp end of the absorber is located in a corner of the wave guide and tapers to a larger cross-sectional area whose center is located approximately in the center of the wave guide. The absorber is relatively short, being of less height than the maximum width of the wave guide.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils

PubMed Central

Banks, Rachel A.; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N.; Riddle, Dawn M.; Li, Chi; Brown, Hannah J.; Zhang, Bin

2017-01-01

Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates. SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo, details of the aggregation

Hypoglycemia induces tau hyperphosphorylation.

PubMed

Lee, Chu-Wan; Shih, Yao-Hsiang; Wu, Shih-Ying; Yang, Tingting; Lin, Chingju; Kuo, Yu-Min

2013-03-01

Cerebral hypoglycemia/hypometabolism is associated with Alzheimer's disease (AD) and is routinely used to assist clinical diagnosis of AD by brain imaging. However, whether cerebral hypoglycemia/hypometabolism contributes to the development of AD or is a response of reduced neuronal activity remains unclear. To investigate the causal relationship, we cultured the differentiated N2a neuroblastoma cells in glucose/pyruvate-deficient media (GDM). Shortly after the N2a cells cultured in the GDM, the mitochondria membrane potential was reduced and the AMP-activated-proteinkinase (AMPK), an energy sensor, was activated. Treatment of GDM not only increased the levels of tau phosphorylation at Ser(262) and Ser(396), but also increased the levels of active forms of GSK3α and GSK3β, two known kinases for tau phosphorylation, of the N2a cells. The levels of activated Akt, a mediator downstream to AMPK and upstream to GSK3α/β, were reduced by the GDM treatment. The effect of hypoglycemia was further examined in vivo by intracerebroventricular (icv) injection of streptozotocin (STZ) to the Wistar rats. STZ selectively injuries glucose transporter type 2-bearing cells which are primarily astrocytes in the rat brain, hence, interrupts glucose transportation from blood vessel to neuron. STZicv injection induced energy crisis in the brain regions surrounding the ventricles, as indicated by higher pAMPK levels in the hippocampus, but not cortex far away from the ventricles. STZ-icv treatment increased the levels of phosphorylated tau and activated GSK3β, but decreased the levels of activated Akt in the hippocampus. The hippocampus-dependent spatial learning and memory was impaired by the STZ-icv treatment. In conclusion, our works suggest that hypoglycemia enhances the AMPK-Akt-GSK3 pathway and leads to tau hyperphosphorylation.

Comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones.

PubMed

Carnes, Stephanie; O'Brien, Stacey; Szewczak, Angelica; Tremeau-Cayel, Lauriane; Rowe, Walter F; McCord, Bruce; Lurie, Ira S

2017-09-01

A comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones has been conducted. Nine different mixtures of bath salts were analyzed in this study. The three different chromatographic techniques were examined using a general set of controlled synthetic cathinones as well as a variety of other synthetic cathinones that exist as positional isomers. Overall 35 different synthetic cathinones were analyzed. A variety of column types and chromatographic modes were examined for developing each separation. For the ultra high performance supercritical fluid chromatography separations, analyses were performed using a series of Torus and Trefoil columns with either ammonium formate or ammonium hydroxide as additives, and methanol, ethanol or isopropanol organic solvents as modifiers. Ultra high performance liquid chromatographic separations were performed in both reversed phase and hydrophilic interaction chromatographic modes using SPP C18 and SPP HILIC columns. Gas chromatography separations were performed using an Elite-5MS capillary column. The orthogonality of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography was examined using principal component analysis. For the best overall separation of synthetic cathinones, the use of ultra high performance supercritical fluid chromatography in combination with gas chromatography is recommended. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils.

PubMed

Gibbons, Garrett S; Banks, Rachel A; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N; Riddle, Dawn M; Li, Chi; Gathagan, Ronald J; Brown, Hannah J; Zhang, Bin; Trojanowski, John Q; Lee, Virginia M-Y

2017-11-22

Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates. SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo , details of the aggregation

cuTauLeaping: A GPU-Powered Tau-Leaping Stochastic Simulator for Massive Parallel Analyses of Biological Systems

PubMed Central

Besozzi, Daniela; Pescini, Dario; Mauri, Giancarlo

2014-01-01

Tau-leaping is a stochastic simulation algorithm that efficiently reconstructs the temporal evolution of biological systems, modeled according to the stochastic formulation of chemical kinetics. The analysis of dynamical properties of these systems in physiological and perturbed conditions usually requires the execution of a large number of simulations, leading to high computational costs. Since each simulation can be executed independently from the others, a massive parallelization of tau-leaping can bring to relevant reductions of the overall running time. The emerging field of General Purpose Graphic Processing Units (GPGPU) provides power-efficient high-performance computing at a relatively low cost. In this work we introduce cuTauLeaping, a stochastic simulator of biological systems that makes use of GPGPU computing to execute multiple parallel tau-leaping simulations, by fully exploiting the Nvidia's Fermi GPU architecture. We show how a considerable computational speedup is achieved on GPU by partitioning the execution of tau-leaping into multiple separated phases, and we describe how to avoid some implementation pitfalls related to the scarcity of memory resources on the GPU streaming multiprocessors. Our results show that cuTauLeaping largely outperforms the CPU-based tau-leaping implementation when the number of parallel simulations increases, with a break-even directly depending on the size of the biological system and on the complexity of its emergent dynamics. In particular, cuTauLeaping is exploited to investigate the probability distribution of bistable states in the Schlögl model, and to carry out a bidimensional parameter sweep analysis to study the oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae. PMID:24663957

Secretion of full-length Tau or Tau fragments in cell culture models. Propagation of Tau in vivo and in vitro.

PubMed

Pérez, Mar; Medina, Miguel; Hernández, Félix; Avila, Jesús

2018-03-05

The microtubule-associated protein Tau plays a crucial role in stabilizing neuronal microtubules. In Tauopathies, Tau loses its ability to bind microtubules, detach from them and forms intracellular aggregates. Increasing evidence in recent years supports the notion that Tau pathology spreading throughout the brain in AD and other Tauopathies is the consequence of the propagation of specific Tau species along neuroanatomically connected brain regions in a so-called "prion-like" manner. A number of steps are assumed to be involved in this process, including secretion, cellular uptake, transcellular transfer and/or seeding, although the precise mechanisms underlying propagation of Tau pathology are not fully understood yet. This review summarizes recent evidence on the nature of the specific Tau species that are propagated and the different mechanisms of Tau pathology spreading.

Measuring B{sup {+-}}{yields}{tau}{sup {+-}}{nu} and B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu} at the Z peak

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

Akeroyd, A. G.; Chen, C.H.; National Center for Theoretical Sciences, Taiwan

2008-06-01

The measurement of B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} at the B factories provides important constraints on the parameter tan{beta}/m{sub H{sup {+-}}} in the context of models with two Higgs doublets. Limits on this decay from e{sup +}e{sup -} collisions at the Z peak were sensitive to the sum of B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} and B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}}. Because of the possibly sizeable contribution from B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} we suggest that a signal for this combination might be observed if the CERN LEP L3 Collaboration used its total data of {approx}3.6x10{sup 6} hadronic decays of the Z boson.more » Moreover, we point out that a future linear collider operating at the Z peak (Giga Z option) could constrain tan{beta}/m{sub H{sup {+-}}} from the sum of these processes with a precision comparable to that anticipated at proposed high luminosity B factories from B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} alone.« less

Determination of the Michel Parameters and the tau Neutrino Helicity in tau Decay

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

Jessop, Colin P.

2003-05-07

Using the CLEO II detector at the e{sup +}e{sup -} storage ring CESR, we have determined the Michel parameters {rho}, {zeta}, and {delta} in {tau}{sup {-+}}{nu}{bar {nu}} decay as well as the {tau} neutrino helicity parameter H{sub {nu}{sub {tau}}} in {tau}{sup {-+}}{pi}{sup 0}{nu} decay. From a data sample of 3.02 x 10{sup 6} {tau} pairs produced at {radical}s = 10.6 GeV, using events of the topology e{sup +}e{sup -} {yields} {tau}{sup +}{tau}{sup -} {yields} (l{sup {+-}}{nu}{bar {nu}})({pi}{sup {-+}}{pi}{sup 0}{nu}) and e{sup +}e{sup -} {yields} {tau}{sup +}{tau}{sup -} {yields} ({pi}{sup {+-}}{pi}{sup 0}{bar {nu}})({pi}{sup {-+}}{pi}{sup 0}{nu}), and the determined sign of h{submore » {nu}{sub {tau}}} [1,2], the combined result of the three samples is: {rho} = 0.747 {+-} 0.010 {+-} 0.006, {zeta} = 1.007 {+-} 0.040 {+-} 0.015, {zeta}{delta} = 0.745 {+-}0.026 {+-}0.009, and h{sub {nu}{sub {tau}}} = -0.995 {+-} 0.010 {+-} 0.003. The results are in agreement with the Standard Model V-A interaction.« less

Ultra Low Energy Binary Decision Diagram Circuits Using Few Electron Transistors

NASA Astrophysics Data System (ADS)

Saripalli, Vinay; Narayanan, Vijay; Datta, Suman

Novel medical applications involving embedded sensors, require ultra low energy dissipation with low-to-moderate performance (10kHz-100MHz) driving the conventional MOSFETs into sub-threshold operation regime. In this paper, we present an alternate ultra-low power computing architecture using Binary Decision Diagram based logic circuits implemented using Single Electron Transistors (SETs) operating in the Coulomb blockade regime with very low supply voltages. We evaluate the energy - performance tradeoff metrics of such BDD circuits using time domain Monte Carlo simulations and compare them with the energy-optimized CMOS logic circuits. Simulation results show that the proposed approach achieves better energy-delay characteristics than CMOS realizations.

Secondary Metabolites in Ramalina terebrata Detected by UHPLC/ESI/MS/MS and Identification of Parietin as Tau Protein Inhibitor.

PubMed

Cornejo, Alberto; Salgado, Francisco; Caballero, Julio; Vargas, Reinaldo; Simirgiotis, Mario; Areche, Carlos

2016-08-18

Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled with photodiode array detector and high resolution mass spectrometry (UHPLC-PDA-Q/Orbitrap/MS/MS). In addition, the extract and the four compounds isolated from this species were tested for the inhibitory activity of tau protein aggregation, which is a protein involved in Alzheimer's disease (AD). All compounds showed null activity with the exception of parietin, which it was able to inhibit aggregation process of tau in a concentration range between 3 µg/mL (10 µM) to 28 µg/mL (100 µM). In addition, we show how parietin interact with tau (306)VQIVYK(311) hexapeptide inside of the microtubule binding domain (4R) with the help of molecular docking experiments. Finally, the constituents present in the methanolic extract could possibly contribute to the established anti-aggregation activity for this extract and this in-depth analysis of the chemical composition of R. terebrata could guide further research into its medicinal properties and potential uses.

Secondary Metabolites in Ramalina terebrata Detected by UHPLC/ESI/MS/MS and Identification of Parietin as Tau Protein Inhibitor

PubMed Central

Cornejo, Alberto; Salgado, Francisco; Caballero, Julio; Vargas, Reinaldo; Simirgiotis, Mario; Areche, Carlos

2016-01-01

Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled with photodiode array detector and high resolution mass spectrometry (UHPLC-PDA-Q/Orbitrap/MS/MS). In addition, the extract and the four compounds isolated from this species were tested for the inhibitory activity of tau protein aggregation, which is a protein involved in Alzheimer’s disease (AD). All compounds showed null activity with the exception of parietin, which it was able to inhibit aggregation process of tau in a concentration range between 3 µg/mL (10 µM) to 28 µg/mL (100 µM). In addition, we show how parietin interact with tau 306VQIVYK311 hexapeptide inside of the microtubule binding domain (4R) with the help of molecular docking experiments. Finally, the constituents present in the methanolic extract could possibly contribute to the established anti-aggregation activity for this extract and this in-depth analysis of the chemical composition of R. terebrata could guide further research into its medicinal properties and potential uses. PMID:27548142

Ultra-stiff metallic glasses through bond energy density design.

PubMed

Schnabel, Volker; Köhler, Mathias; Music, Denis; Bednarcik, Jozef; Clegg, William J; Raabe, Dierk; Schneider, Jochen M

2017-07-05

The elastic properties of crystalline metals scale with their valence electron density. Similar observations have been made for metallic glasses. However, for metallic glasses where covalent bonding predominates, such as metalloid metallic glasses, this relationship appears to break down. At present, the reasons for this are not understood. Using high energy x-ray diffraction analysis of melt spun and thin film metallic glasses combined with density functional theory based molecular dynamics simulations, we show that the physical origin of the ultrahigh stiffness in both metalloid and non-metalloid metallic glasses is best understood in terms of the bond energy density. Using the bond energy density as novel materials design criterion for ultra-stiff metallic glasses, we are able to predict a Co 33.0 Ta 3.5 B 63.5 short range ordered material by density functional theory based molecular dynamics simulations with a high bond energy density of 0.94 eV Å -3 and a bulk modulus of 263 GPa, which is 17% greater than the stiffest Co-B based metallic glasses reported in literature.

Ultra-flexible Piezoelectric Devices Integrated with Heart to Harvest the Biomechanical Energy

NASA Astrophysics Data System (ADS)

Lu, Bingwei; Chen, Ying; Ou, Dapeng; Chen, Hang; Diao, Liwei; Zhang, Wei; Zheng, Jun; Ma, Weiguo; Sun, Lizhong; Feng, Xue

2015-11-01

Power supply for medical implantable devices (i.e. pacemaker) always challenges not only the surgery but also the battery technology. Here, we report a strategy for energy harvesting from the heart motion by using ultra-flexible piezoelectric device based on lead zirconate titanate (PZT) ceramics that has most excellent piezoelectricity in commercial materials, without any burden or damage to hearts. Experimental swine are selected for in vivo test with different settings, i.e. opened chest, close chest and awake from anesthesia, to simulate the scenario of application in body due to their hearts similar to human. The results show the peak-to-peak voltage can reach as high as 3 V when the ultra-flexible piezoelectric device is fixed from left ventricular apex to right ventricle. This demonstrates the possibility and feasibility of fully using the biomechanical energy from heart motion in human body for sustainably driving implantable devices.

ENERGY INTAKE FROM ULTRA-PROCESSED FOODS AMONG ADOLESCENTS.

PubMed

D'Avila, Helen Freitas; Kirsten, Vanessa Ramos

2017-01-01

To evaluate the consumption of ultra-processed foods and related factors in adolescents. This is a cross-sectional study conducted with 784 adolescents (both sexes and aged between 12 and 19 years) from public and private schools in the municipality of Palmeira das Missões, Brazil. Food consumption was recorded by the semiquantitative questionnaire of frequency of food consumption and converted to energy (kcal/day). Foods were classified as minimally processed, group 1 (G1); processed foods, group 2 (G2); and ultra-processed foods, group 3 (G3). The variables evaluated were sex, socioeconomic class, color, physical activity, body mass index, and blood pressure levels. In the comparison of quantitative variables, the Mann-Whitney test and the Kruskal-Wallis H test were used. To adjust the differences between the groups, considering the effects of total calories, the covariance analysis test (ANCOVA) was applied. The median of the total energy consumption was 3,039.8 kcal, and that of ultra-processed foods was 1,496.5 kcal/day (49.23%). The caloric intake from foods in G1, G2, and G3 did not differ according to the skin color of the adolescents. Those belonging to socioeconomic classes C and D are the most frequent consumers of calories from G2 and G3 (p<0.001). Underactive teens consume fewer calories from minimally processed foods. Eutrophic adolescents present higher consumption of G3 foods (p<0.001) when compared to those who are overweight. The consumption of ultra-processed foods was associated with socioeconomic level, physical activity level, and nutritional status.

Search for the Higgs Boson Decaying to Two Tau Leptons in $$p\\bar{p}$$ Collisions at a Center of Mass Energy of 1.96 Tev

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

Elagin, Andrey Lvovich

2011-12-01

A search for the Higgs boson decaying tomore » $$\\tau\\tau$$ using 7.8~fb$$^{-1}$$ of $$p\\bar{p}$$ collisions at 1.96~TeV collected with CDF II detector is presented. The search is sensitive to four production mechanisms of the Higgs boson: ggH, WH, ZH and VBF. Modes where one tau decay leptonically, and another decay, hadronically, are considered. Two novel techniques are developed and used in the search. A Probabilistic Particle Flow Algorithm is used for energy measurements of the hadronic tau candidates. The signal is discriminated from backgrounds by the Missing Mass Calculator, which allows for full invariant mass reconstruction of $$\\tau\\tau$$ pair. The data are found to be consistent with the background only hypothesis. Therefore a 95\\% confidence level upper limit on the Standard Model Higgs boson cross section was set. At $$M_H$$=$120~GeV/$c^2$ observed limit is 14.9$$\\times\\sigma_{SM}\\times Br (H → ττ)$$.« less

No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau).

PubMed

Krut, Jan J; Price, Richard W; Zetterberg, Henrik; Fuchs, Dietmar; Hagberg, Lars; Yilmaz, Aylin; Cinque, Paola; Nilsson, Staffan; Gisslén, Magnus

2017-07-04

The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. With a cross-sectional retrospective design, p-tau, total tau (t-tau), neopterin and HIV-RNA were measured in CSF together with plasma HIV-RNA and blood CD4 + T-cells of 225 HIV-infected patients <50 y of age, subdivided into 3 groups: untreated neuroasymptomatic (NA) (n = 145), on suppressive antiretroviral treatment (cART) (n = 49), and HIV-associated dementia (HAD) (n = 31). HIV-negative healthy subjects served as controls (n = 79). P-tau was not significantly higher in any HIV-infected group compared to HIV-negative controls. Significant increases in t-tau were found as expected in patients with HAD compared to NA, cART, and control groups (p < 0.001 ). P-tau was not higher in HIV-infected patients compared to uninfected controls, thus failing to support a role for premature or accelerated brain aging in HIV infection.

Mass composition studies of Ultra High Energy cosmic rays through the measurement of the Muon Production Depths at the Pierre Auger Observatory

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

Collica, Laura

The Pierre Auger Observatory (Auger) in Argentina studies Ultra High Energy Cosmic Rays (UHECRs) physics. The flux of cosmic rays at these energies (above 1018 eV) is very low (less than 100 particle/km2-year) and UHECR properties must be inferred from the measurements of the secondary particles that the cosmic ray primary produces in the atmosphere. These particles cascades are called Extensive Air Showers (EAS) and can be studied at ground by deploying detectors covering large areas. The EAS physics is complex, and the properties of secondary particles depend strongly on the first interaction, which takes place at an energy beyondmore » the ones reached at accelerators. As a consequence, the analysis of UHECRs is subject to large uncertainties and hence many of their properties, in particular their composition, are still unclear. Two complementary techniques are used at Auger to detect EAS initiated by UHE- CRs: a 3000 km2 surface detector (SD) array of water Cherenkov tanks which samples particles at ground level and fluorescence detectors (FD) which collect the ultraviolet light emitted by the de-excitation of nitrogen nuclei in the atmosphere, and can operate only in clear, moonless nights. Auger is the largest cosmic rays detector ever built and it provides high-quality data together with unprecedented statistics. The main goal of this thesis is the measurement of UHECR mass composition using data from the SD of the Pierre Auger Observatory. Measuring the cosmic ray composition at the highest energies is of fundamental importance from the astrophysical point of view, since it could discriminate between different scenarios of origin and propagation of cosmic rays. Moreover, mass composition studies are of utmost importance for particle physics. As a matter of fact, knowing the composition helps in exploring the hadronic interactions at ultra-high energies, inaccessible to present accelerator experiments.« less

Ultra-flexible Piezoelectric Devices Integrated with Heart to Harvest the Biomechanical Energy

PubMed Central

Lu, Bingwei; Chen, Ying; Ou, Dapeng; Chen, Hang; Diao, Liwei; Zhang, Wei; Zheng, Jun; Ma, Weiguo; Sun, Lizhong; Feng, Xue

2015-01-01

Power supply for medical implantable devices (i.e. pacemaker) always challenges not only the surgery but also the battery technology. Here, we report a strategy for energy harvesting from the heart motion by using ultra-flexible piezoelectric device based on lead zirconate titanate (PZT) ceramics that has most excellent piezoelectricity in commercial materials, without any burden or damage to hearts. Experimental swine are selected for in vivo test with different settings, i.e. opened chest, close chest and awake from anesthesia, to simulate the scenario of application in body due to their hearts similar to human. The results show the peak-to-peak voltage can reach as high as 3 V when the ultra-flexible piezoelectric device is fixed from left ventricular apex to right ventricle. This demonstrates the possibility and feasibility of fully using the biomechanical energy from heart motion in human body for sustainably driving implantable devices. PMID:26538375

ENERGY INTAKE FROM ULTRA-PROCESSED FOODS AMONG ADOLESCENTS

PubMed Central

D’Avila, Helen Freitas; Kirsten, Vanessa Ramos

2017-01-01

ASTRACT Objective: To evaluate the consumption of ultra-processed foods and related factors in adolescents. Methods: This is a cross-sectional study conducted with 784 adolescents (both sexes and aged between 12 and 19 years) from public and private schools in the municipality of Palmeira das Missões, Brazil. Food consumption was recorded by the semiquantitative questionnaire of frequency of food consumption and converted to energy (kcal/day). Foods were classified as minimally processed, group 1 (G1); processed foods, group 2 (G2); and ultra-processed foods, group 3 (G3). The variables evaluated were sex, socioeconomic class, color, physical activity, body mass index, and blood pressure levels. In the comparison of quantitative variables, the Mann-Whitney test and the Kruskal-Wallis H test were used. To adjust the differences between the groups, considering the effects of total calories, the covariance analysis test (ANCOVA) was applied. Results: The median of the total energy consumption was 3,039.8 kcal, and that of ultra-processed foods was 1,496.5 kcal/day (49.23%). The caloric intake from foods in G1, G2, and G3 did not differ according to the skin color of the adolescents. Those belonging to socioeconomic classes C and D are the most frequent consumers of calories from G2 and G3 (p<0.001). Underactive teens consume fewer calories from minimally processed foods. Eutrophic adolescents present higher consumption of G3 foods (p<0.001) when compared to those who are overweight. Conclusions: The consumption of ultra-processed foods was associated with socioeconomic level, physical activity level, and nutritional status. PMID:28977317

Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates*

PubMed Central

Tennstaedt, Annette; Pöpsel, Simon; Truebestein, Linda; Hauske, Patrick; Brockmann, Anke; Schmidt, Nina; Irle, Inga; Sacca, Barbara; Niemeyer, Christof M.; Brandt, Roland; Ksiezak-Reding, Hanna; Tirniceriu, Anca Laura; Egensperger, Rupert; Baldi, Alfonso; Dehmelt, Leif; Kaiser, Markus; Huber, Robert; Clausen, Tim; Ehrmann, Michael

2012-01-01

Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control. So far, however, no HtrA protease is known that degrades protein aggregates. We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations. These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed. PMID:22535953

Ultra-high density aligned Carbon-nanotube with controled nano-morphology for supercapacitors

NASA Astrophysics Data System (ADS)

Ghaffari, Mehdi; Zhao, Ran; Liu, Yang; Zhou, Yue; Cheng, Jiping; Guzman de Villoria, Roberto; Wardle, B. L.; Zhang, Q. M.

2012-02-01

Recent advances in fabricating controlled-morphology vertically aligned carbon nanotubes (VA-CNTs) with ultrahigh volume fractioncreate unique opportunities for developing unconventional supercapacitors with ultra-high energy density, power density, and long charge/discharge cycle life.Continuous paths through inter-VA-CNT channels allow fast ion transport, and high electrical conduction of the aligned CNTs in the composite electrodes lead to fast discharge speed. We investigate the charge-discharge characteristics of VA-CNTs with >20 vol% of CNT and ionic liquids as electrolytes. By employing both the electric and electromechanical spectroscopes, as well as nanostructured materials characterization, the ion transport and storage behaviors in porous electrodes are studied. The results suggest pathways for optimizing the electrode morphology in supercapacitorsusing ultra-high volume fraction VA-CNTs to further enhance performance.

Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

PubMed Central

Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

2015-01-01

Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

Quantile Regression for Analyzing Heterogeneity in Ultra-high Dimension

PubMed Central

Wang, Lan; Wu, Yichao

2012-01-01

Ultra-high dimensional data often display heterogeneity due to either heteroscedastic variance or other forms of non-location-scale covariate effects. To accommodate heterogeneity, we advocate a more general interpretation of sparsity which assumes that only a small number of covariates influence the conditional distribution of the response variable given all candidate covariates; however, the sets of relevant covariates may differ when we consider different segments of the conditional distribution. In this framework, we investigate the methodology and theory of nonconvex penalized quantile regression in ultra-high dimension. The proposed approach has two distinctive features: (1) it enables us to explore the entire conditional distribution of the response variable given the ultra-high dimensional covariates and provides a more realistic picture of the sparsity pattern; (2) it requires substantially weaker conditions compared with alternative methods in the literature; thus, it greatly alleviates the difficulty of model checking in the ultra-high dimension. In theoretic development, it is challenging to deal with both the nonsmooth loss function and the nonconvex penalty function in ultra-high dimensional parameter space. We introduce a novel sufficient optimality condition which relies on a convex differencing representation of the penalized loss function and the subdifferential calculus. Exploring this optimality condition enables us to establish the oracle property for sparse quantile regression in the ultra-high dimension under relaxed conditions. The proposed method greatly enhances existing tools for ultra-high dimensional data analysis. Monte Carlo simulations demonstrate the usefulness of the proposed procedure. The real data example we analyzed demonstrates that the new approach reveals substantially more information compared with alternative methods. PMID:23082036

RNA stores tau reversibly in complex coacervates

PubMed Central

Lin, Yanxian; Eschmann, Neil A.; Zhou, Hongjun; Rauch, Jennifer N.; Hernandez, Israel; Guzman, Elmer; Kosik, Kenneth S.; Han, Songi

2017-01-01

Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable β-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

High resolution electron energy loss spectroscopy of spin waves in ultra-thin film - The return of the adiabatic approximation?

NASA Astrophysics Data System (ADS)

Ibach, Harald

2014-12-01

The paper reports on recent considerable improvements in electron energy loss spectroscopy (EELS) of spin waves in ultra-thin films. Spin wave spectra with 4 meV resolution are shown. The high energy resolution enables the observation of standing modes in ultra-thin films in the wave vector range of 0.15 Å- 1 < q|| < 0.3 Å- 1. In this range, Landau damping is comparatively small and standing spin wave modes are well-defined Lorentzians for which the adiabatic approximation is well suited, an approximation which was rightly dismissed by Mills and collaborators for spin waves near the Brillouin zone boundary. With the help of published exchange coupling constants, the Heisenberg model, and a simple model for the spectral response function, experimental spectra for Co-films on Cu(100) as well as for Co films capped with further copper layers are successfully simulated. It is shown that, depending on the wave vector and film thickness, the most prominent contribution to the spin wave spectrum may come from the first standing mode, not from the so-called surface mode. In general, the peak position of a low-resolution spin wave spectrum does not correspond to a single mode. A discussion of spin waves based on the "dispersion" of the peak positions in low resolution spectra is therefore subject to errors.

Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain

PubMed Central

Maphis, Nicole; Xu, Guixiang; Kokiko-Cochran, Olga N.; Jiang, Shanya; Cardona, Astrid; Ransohoff, Richard M.; Lamb, Bruce T.

2015-01-01

Pathological aggregation of tau is a hallmark of Alzheimer’s disease and related tauopathies. We have previously shown that the deficiency of the microglial fractalkine receptor (CX3CR1) led to the acceleration of tau pathology and memory impairment in an hTau mouse model of tauopathy. Here, we show that microglia drive tau pathology in a cell-autonomous manner. First, tau hyperphosphorylation and aggregation occur as early as 2 months of age in hTauCx3cr1−/− mice. Second, CD45+ microglial activation correlates with the spatial memory deficit and spread of tau pathology in the anatomically connected regions of the hippocampus. Third, adoptive transfer of purified microglia derived from hTauCx3cr1−/− mice induces tau hyperphosphorylation within the brains of non-transgenic recipient mice. Finally, inclusion of interleukin 1 receptor antagonist (Kineret®) in the adoptive transfer inoculum significantly reduces microglia-induced tau pathology. Together, our results suggest that reactive microglia are sufficient to drive tau pathology and correlate with the spread of pathological tau in the brain. PMID:25833819

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Search for the standard model Higgs boson in tau final states.

PubMed

Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Ancu, L S; Andeen, T; Anzelc, M S; Aoki, M; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Atramentov, O; Avila, C; Backusmayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calfayan, P; Calpas, B; Calvet, S; Cammin, J; Carrasco-Lizarraga, M A; Carrera, E; Carvalho, W; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Cho, D K; Choi, S; Choudhary, B; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cuplov, V; Cutts, D; Cwiok, M; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; DeVaughan, K; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Escalier, M; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gómez, B; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jamin, D; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J-P; Kozelov, A V; Kraus, J; Kuhl, T; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, W M; Leflat, A; Lellouch, J; Li, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Mättig, P; Magerkurth, A; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Maravin, Y; Martin, B; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Mendoza, L; Menezes, D; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, A; Meyer, J; Mitrevski, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; Obrant, G; Ochando, C; Onoprienko, D; Orduna, J; Oshima, N; Osman, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padilla, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Popov, A V; Potter, C; Prado da Silva, W L; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Ranjan, K; Ratoff, P N; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Sumowidagdo, S; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Torchiani, I; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; Vachon, B; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vilanova, D; Vint, P; Vokac, P; Voutilainen, M; Wagner, R; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Welty-Rieger, L; Wenger, A; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L; Zutshi, V; Zverev, E G

2009-06-26

We present a search for the standard model Higgs boson using hadronically decaying tau leptons, in 1 fb(-1) of data collected with the D0 detector at the Fermilab Tevatron pp collider. We select two final states: tau+/- plus missing transverse energy and b jets, and tau+ tau- plus jets. These final states are sensitive to a combination of associated W/Z boson plus Higgs boson, vector boson fusion, and gluon-gluon fusion production processes. The observed ratio of the combined limit on the Higgs production cross section at the 95% C.L. to the standard model expectation is 29 for a Higgs boson mass of 115 GeV.

Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology.

PubMed

Song, Lixin; Lu, Sherry X; Ouyang, Xuesong; Melchor, Jerry; Lee, Julie; Terracina, Giuseppe; Wang, Xiaohai; Hyde, Lynn; Hess, J Fred; Parker, Eric M; Zhang, Lili

2015-03-26

Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and several other neurodegenerative diseases. Tau mutations are associated with frontotemperal dementia with parkinsonism on chromosome 17 (FTDP-17). rTg4510 mice overexpress human tau carrying the P301L FTDP-17 mutation and develop robust NFT-like pathology at 4-5 months of age. The current study is aimed at characterizing the rTg4510 mice to better understand the genesis of tau pathology and to better enable the use of this model in drug discovery efforts targeting tau pathology. Using a panel of immunoassays, we analyzed the age-dependent formation of pathological tau in rTg4510 mice and our data revealed a steady age-dependent accumulation of pathological tau in the insoluble fraction of brain homogenates. The pathological tau was associated with multiple post-translational modifications including aggregation, phosphorylation at a wide variety of sites, acetylation, ubiquitination and nitration. The change of most tau species reached statistical significance at the age of 16 weeks. There was a strong correlation between the different post-translationally modified tau species in this heterogeneous pool of pathological tau. Total tau in the cerebrospinal fluid (CSF) displayed a multiphasic temporal profile distinct from the steady accumulation of pathological tau in the brain. Female rTg4510 mice displayed significantly more aggressive accumulation of pathological tau in the brain and elevation of total tau in CSF than their male littermates. The immunoassays described here were used to generate the most comprehensive description of the changes in various tau species across the lifespan of the rTg4510 mouse model. The data indicate that development of tauopathy in rTg4510 mice involves the accumulation of a pool of pathological tau that carries multiple post-translational modifications, a process that can be

Ultra-fast switching of light by absorption saturation in vacuum ultra-violet region.

PubMed

Yoneda, Hitoki; Inubushi, Yuichi; Tanaka, Toshihiro; Yamaguchi, Yuta; Sato, Fumiya; Morimoto, Shunsuke; Kumagai, Taisuke; Nagasono, Mitsuru; Higashiya, Atsushi; Yabashi, Makina; Ishikawa, Tetsuya; Ohashi, Haruhiko; Kimura, Hiroaki; Kitamura, Hikaru; Kodama, Ryosuke

2009-12-21

Advances in free electron lasers producing high energy photons [Nat. Photonics 2(9), 555-559 (2008)] are expected to open up a new science of nonlinear optics of high energy photons. Specifically, lasers of photon energy higher than the plasma frequency of a metal can show new interaction features because they can penetrate deeply into metals without strong reflection. Here we show the observation of ultra-fast switching of vacuum ultra-violet (VUV) light caused by saturable absorption of a solid metal target. A strong gating is observed at energy fluences above 6J/cm2 at wavelength of 51 nm with tin metal thin layers. The ratio of the transmission at high intensity to low intensity is typically greater than 100:1. This means we can design new nonlinear photonic devices such as auto-correlator and pulse slicer for the VUV region.

Determination of the Michel parameters and the {tau} neutrino helicity in {tau} decay

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

CLEO Collaboration

1997-11-01

Using the CLEO II detector at the Cornell Electron Storage Ring operated at {radical} (s) =10.6GeV, we have determined the Michel parameters {rho}, {xi}, and {delta} in {tau}{sup {minus_plus}}{r_arrow}l{sup {minus_plus}}{nu}{bar {nu}} decay as well as the {tau} neutrino helicity parameter h{sub {nu}{sub {tau}}} in {tau}{sup {minus_plus}}{r_arrow}{pi}{sup {minus_plus}}{pi}{sup 0}{nu} decay. From a data sample of 3.02{times}10{sup 6} produced {tau} pairs we analyzed events of the topologies e{sup +}e{sup {minus}}{r_arrow}{tau}{sup +}{tau}{sup {minus}}{r_arrow}(l{sup {plus_minus}}{nu}{bar {nu}})({pi}{sup {minus_plus}}{pi}{sup 0}{nu}) and e{sup +}e{sup {minus}}{r_arrow}{tau}{sup +}{tau}{sup {minus}}{r_arrow}({pi}{sup {plus_minus}}{pi}{sup 0}{bar {nu}})({pi}{sup {minus_plus}}{pi}{sup 0}{nu}). We obtain {rho}=0.747{rho}=0.747{plus_minus}0.010{plus_minus}0.006, {xi}=1.007{plus_minus}0.040{plus_minus}0.015, {xi}{delta}=0.745{plus_minus}0.026{plus_minus}0.009, and h{sub {nu}{sub {tau}}}={minus}0.995{plus_minus}0.010{plus_minus}0.003, where we have used the previouslymore » determined sign of h{sub {nu}{sub {tau}}} [ARGUS Collaboration, H. Albrecht {ital et al.}, Z. Phys. C {bold 58}, 61 (1993); Phys. Lett. B {bold 349}, 576 (1995)]. We also present the Michel parameters as determined from the electron and muon samples separately. All results are in agreement with the standard model V{minus}A interaction. {copyright} {ital 1997} {ital The American Physical Society}« less

Molecular mechanism of tau aggregation induced by anionic and cationic dyes.

PubMed

Lira-De León, Karla I; García-Gutiérrez, Ponciano; Serratos, Iris N; Palomera-Cárdenas, Marianela; Figueroa-Corona, María Del P; Campos-Peña, Victoria; Meraz-Ríos, Marco A

2013-01-01

Abnormal tau filaments are a hallmark of Alzheimer's disease. Anionic dyes such as Congo Red, Thiazine Red, and Thioflavin S are able to induce tau fibrillization in vitro. SH-SY5Y cells were incubated with each dye for seven days leading to intracellular aggregates of tau protein, with different morphological characteristics. Interestingly, these tau aggregates were not observed when the Methylene Blue dye was added to the cell culture. In order to investigate the molecular mechanisms underlying this phenomenon, we developed a computational model for the interaction of the tau paired helical filament (PHF) core with every dye by docking analysis. The polar/electrostatic and nonpolar contribution to the free binding energy in the tau PHF core-anionic dye interaction was determined. We found that the tau PHF core can generate a positive net charge within the binding site localized at residuesLys311 and Lys340 (numbering according to the longest isoform hTau40). These residues are important for the binding affinity of the negative charges present in the anionic dyes causing an electrostatic environment that stabilizes the complex. Tau PHF core protofibril-Congo Red interaction has a stronger binding affinity compared to Thiazine Red or Thioflavin S. By contrast, the cationic dye Methylene Blue does not bind to nor stabilize the tau PHF core protofibrils. These results characterize the driving forces responsible for the binding of tau to anionic dyes leading to their self-aggregation and suggest that Methylene Blue may act as a destabilizing agent of tau aggregates.

DOPA Decarboxylase Modulates Tau Toxicity.

PubMed

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Tau-Induced Ca2+/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation.

PubMed

Wei, Yu-Ping; Ye, Jin-Wang; Wang, Xiong; Zhu, Li-Ping; Hu, Qing-Hua; Wang, Qun; Ke, Dan; Tian, Qing; Wang, Jian-Zhi

2018-04-01

Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca 2+ concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca 2+ concentration with a simultaneous increase in the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca 2+ /CaMKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation of the Ca 2+ /calmodulin complex abolished the okadaic acid-induced tau hyperphosphorylation in the nuclear fraction. We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca 2+ /CaMKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca 2+ concentration may induce a self-perpetuating harmful loop to promote neurodegeneration.

Enhancing electrical energy storage capability of dielectric polymer nanocomposites via the room temperature Coulomb blockade effect of ultra-small platinum nanoparticles.

PubMed

Wang, Liwei; Huang, Xingyi; Zhu, Yingke; Jiang, Pingkai

2018-02-14

Introducing a high dielectric constant (high-k) nanofiller into a dielectric polymer is the most common way to achieve flexible nanocomposites for electrostatic energy storage devices. However, the significant decrease of breakdown strength and large increase of dielectric loss has long been known as the bottleneck restricting the enhancement of practical energy storage capability of the nanocomposites. In this study, by introducing ultra-small platinum (<2 nm) nanoparticles, high-k polymer nanocomposites with high breakdown strength and low dielectric loss were prepared successfully. Core-shell structured polydopamine@BaTiO 3 (PDA@BT) and core-satellite ultra-small platinum decorated PDA@BT (Pt@PDA@BT) were used as nanofillers. Compared with PDA@BT nanocomposites, the maximum discharged energy density of the Pt@PDA@BT nanocomposites is increased by nearly 70% because of the improved energy storage efficiency. This research provides a simple, promising and unique way to enhance energy storage capability of high-k polymer nanocomposites.

Using Human iPSC-Derived Neurons to Model TAU Aggregation

PubMed Central

Verheyen, An; Diels, Annick; Dijkmans, Joyce; Oyelami, Tutu; Meneghello, Giulia; Mertens, Liesbeth; Versweyveld, Sofie; Borgers, Marianne; Buist, Arjan; Peeters, Pieter; Cik, Miroslav

2015-01-01

Alzheimer’s disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. PMID:26720731

Ultra High Energy Neutrinos and Cosmic Rays: a “Vision” for the next decade

NASA Astrophysics Data System (ADS)

Santangelo, A.

2007-04-01

Ultra High Energy Neutrinos, with energies from a few 1018 eV to beyond the decade of 1020 eV, and Cosmic Rays with E≥5×10 eV appear to be the only suitable messengers to explore the Universe at frontier energies, where radiation is expected to be produced under the most extreme physical conditions. Observations of these UHE particles will certainly provide new information on the sources and on the physical mechanisms able to accelerate these extreme messengers to macroscopic energies. Moreover, they might, also, provide evidence of yet unknown physics or of exotic particles, relics of the early Universe. To reach these goals, innovative experiments with larger effective aperture (A≥10 kmsr) and good understanding of systematic uncertainties (less than ˜ 10%) must be developed. The ground-based Pierre Auger Observatory, whose southern site is expected to be completed in Malargue, Argentina by the end of 2006, will surely provide, in the near future, a more solid observational scenario (Flux, Spectral shape, Composition) for UHE Cosmic Rays (UHECR). However, only space-based observatories can reach the effective area necessary to systematically explore the UHE Universe. In the present paper 1.) we present the Science Rationale behind UHE studies; 2.) we review the status of current experimental efforts, with main emphasis on the actual generation of space-based observatories; 3.) we briefly discuss the science goals, requirements, and R&D of a “next-generation” space-based mission for UHE observations. To develop such a challenging and innovative observatory for UHE particles, the ESA “Cosmic Vision 2015-2025” long term plan provides certainly an unique opportunity.

Two novel kinases phosphorylate tau and the KSP site of heavy neurofilament subunits in high stoichiometric ratios.

PubMed

Roder, H M; Ingram, V M

1991-11-01

We have identified, purified, and characterized two neurofilament/tau kinases from bovine brain, PK36 and PK40, with apparent Mr of 36,000 and 40,000 and with novel biochemical properties. A specially designed immunoassay for phosphorylated epitopes in neurofilament (NF) proteins was used in the early stages of the purification. Neither kinase is closely associated with the cytoskeleton. Both kinases phosphorylate bovine intermediate (NF-M) and heavy (NF-H) NF subunits and also bovine tau at the expected KSP sequences, though other sites cannot be ruled out. In human paired helical filaments, tau, phosphorylated at these same KSP sites, is a major characterized constituent. Neither kinase is activated by the usual second messengers. Tau and the above NF subunits are phosphorylated in high stoichiometric ratios. In the intermediate NF subunit, all the expected sites appear to be phosphorylated, but in the heavy NF subunit only 7 out of the greater than 40 expected sites can be phosphorylated by our kinases. We demonstrate that both kinases can induce considerable shifts of apparent Mr with SDS-PAGE for tau and, for the first time in vitro, also for the intermediate NF subunit. Interestingly, PK36 and particularly PK40 are strongly inhibited by an excess of free ATP. We propose that during normal aging, and in Alzheimer's disease, age-related mitochondrial dysfunction would reduce ATP levels, which in turn might release the neurofilament/tau kinase from inhibition with consequent paired helical filament formation.

Antisense reduction of tau in adult mice protects against seizures.

PubMed

DeVos, Sarah L; Goncharoff, Dustin K; Chen, Guo; Kebodeaux, Carey S; Yamada, Kaoru; Stewart, Floy R; Schuler, Dorothy R; Maloney, Susan E; Wozniak, David F; Rigo, Frank; Bennett, C Frank; Cirrito, John R; Holtzman, David M; Miller, Timothy M

2013-07-31

Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.

Detection of tau neutrinos by imaging air Cherenkov telescopes

NASA Astrophysics Data System (ADS)

Góra, D.; Bernardini, E.

2016-09-01

This paper investigates the potential to detect tau neutrinos in the energy range of 1-1000 PeV searching for very inclined showers with imaging Cherenkov telescopes. A neutrino induced tau lepton escaping from the Earth may decay and initiate an air shower which can be detected by a fluorescence or Cherenkov telescope. We present here a study of the detection potential of Earth-skimming neutrinos taking into account neutrino interactions in the Earth crust, local matter distributions at various detector sites, the development of tau-induced showers in air and the detection of Cherenkov photons with IACTs. We analyzed simulated shower images on the camera focal plane and implemented generic reconstruction chains based on Hillas parameters. We find that present IACTs can distinguish air showers induced by tau neutrinos from the background of hadronic showers in the PeV-EeV energy range. We present the neutrino trigger efficiency obtained for a few configurations being considered for the next-generation Cherenkov telescopes, i.e. the Cherenkov Telescope Array. Finally, for a few representative neutrino spectra expected from astrophysical sources, we compare the expected event rates at running IACTs to what is expected for the dedicated IceCube neutrino telescope.

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.

PubMed

Gisslén, Magnus; Krut, Jan; Andreasson, Ulf; Blennow, Kaj; Cinque, Paola; Brew, Bruce J; Spudich, Serena; Hagberg, Lars; Rosengren, Lars; Price, Richard W; Zetterberg, Henrik

2009-12-22

Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.

On the origin of ultra high energy cosmic rays: subluminal and superluminal relativistic shocks

NASA Astrophysics Data System (ADS)

Meli, A.; Becker, J. K.; Quenby, J. J.

2008-12-01

Aims: The flux of ultra high energy cosmic rays (UHECRs) at E > 1018.5 eV is believed to arise in plasma shock environments in extragalactic sources. In this paper, we present a systematic study of cosmic ray (CR) particle acceleration by relativistic shocks, in particular concerning the dependence on bulk Lorentz factor and the angle between the magnetic field and the shock flow. The contribution to the observed diffuse CR spectrum provided by the accelerated particles is discussed. Methods: For the first time, Monte Carlo simulations for super- and subluminal shocks are extended to boost factors up to Γ = 1000 and systematically compared. The source spectra derived are translated into the expected diffuse proton flux from astrophysical sources by folding the spectra with the spatial distribution of active galactic nuclei (AGN) and gamma ray bursts (GRBs). Results of these predictions are compared with UHECR data. Results: While superluminal shocks are shown to be inefficient at providing acceleration to the highest energies (E > 1018.5 eV), subluminal shocks may provide particles up to 1021 eV, limited only by the Hillas-criterion. In the subluminal case, we find that mildly-relativistic shocks, thought to occur in jets of AGN (Γ ~ 10-30), yield energy spectra of dN/dE ~ E-2. Highly relativistic shocks expected in GRBs (100 < Γ < 1000), on the other hand, produce spectra as flat as ~ E-1.0 above 109.5 GeV. The model results are compared with the measured flux of CRs at the highest energies and it is shown that, while AGN spectra provide an excellent fit, GRB spectra are too flat to explain the observed flux. The first evidence of a correlation between the CR flux above 5.7 × 1010 GeV and the distribution of AGN provided by Auger are explained by our model. Although GRBs are excluded as the principle origin of UHECRs, neutrino production is expected in these sources either in mildly or highly relativistic shocks. In particular, superluminal shocks in GRBs may

The Lateral Trigger Probability function for the Ultra-High Energy Cosmic Ray showers detected by the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antičić, T.; Anzalone, A.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Bäcker, T.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Beatty, J. J.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; Benzvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Caballero-Mora, K. S.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chudoba, J.; Clay, R. W.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Domenico, M.; de Donato, C.; de Jong, S. J.; de La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; de Mitri, I.; de Souza, V.; de Vries, K. D.; Decerprit, G.; Del Peral, L.; Deligny, O.; Dembinski, H.; Dhital, N.; di Giulio, C.; Diaz, J. C.; Díaz Castro, M. L.; Diep, P. N.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; Dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; Facal San Luis, P.; Fajardo Tapia, I.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Ferrero, A.; Fick, B.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Gascon, A.; Gemmeke, H.; Gesterling, K.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gonçalves, P.; Gonzalez, D.; Gonzalez, J. G.; Gookin, B.; Góra, D.; Gorgi, A.; Gouffon, P.; Gozzini, S. R.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Guzman, A.; Hague, J. D.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Hrabovský, M.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jarne, C.; Jiraskova, S.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuehn, F.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; Lautridou, P.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Lemiere, A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Mićanović, S.; Micheletti, M. I.; Miller, W.; Miramonti, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Morris, C.; Mostafá, M.; Moura, C. A.; Mueller, S.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Nhung, P. T.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Nyklicek, M.; Oehlschläger, J.; Olinto, A.; Oliva, P.; Olmos-Gilbaja, V. M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Parsons, R. D.; Pastor, S.; Paul, T.; Pech, M.; Pȩkala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Phan, N.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Ponce, V. H.; Pontz, M.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Robledo, C.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-D'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Stapleton, J.; Stasielak, J.; Stephan, M.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tamashiro, A.; Tapia, A.; Tartare, M.; Taşcău, O.; Tavera Ruiz, C. G.; Tcaciuc, R.; Tegolo, D.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tiwari, D. K.; Tkaczyk, W.; Todero Peixoto, C. J.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Warner, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Westerhoff, S.; Whelan, B. J.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Winders, L.; Winnick, M. G.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Ziolkowski, M.

2011-12-01

In this paper we introduce the concept of Lateral Trigger Probability (LTP) function, i.e., the probability for an Extensive Air Shower (EAS) to trigger an individual detector of a ground based array as a function of distance to the shower axis, taking into account energy, mass and direction of the primary cosmic ray. We apply this concept to the surface array of the Pierre Auger Observatory consisting of a 1.5 km spaced grid of about 1600 water Cherenkov stations. Using Monte Carlo simulations of ultra-high energy showers the LTP functions are derived for energies in the range between 1017 and 1019 eV and zenith angles up to 65°. A parametrization combining a step function with an exponential is found to reproduce them very well in the considered range of energies and zenith angles. The LTP functions can also be obtained from data using events simultaneously observed by the fluorescence and the surface detector of the Pierre Auger Observatory (hybrid events). We validate the Monte Carlo results showing how LTP functions from data are in good agreement with simulations.

PHYSICS OF OUR DAYS Physical conditions in potential accelerators of ultra-high-energy cosmic rays: updated Hillas plot and radiation-loss constraints

NASA Astrophysics Data System (ADS)

Ptitsyna, Kseniya V.; Troitsky, Sergei V.

2010-10-01

We review basic constraints on the acceleration of ultra-high-energy (UHE) cosmic rays (CRs) in astrophysical sources, namely, the geometric (Hillas) criterion and the restrictions from radiation losses in different acceleration regimes. Using the latest available astrophysical data, we redraw the Hillas plot and find potential UHECR accelerators. For the acceleration in the central engines of active galactic nuclei, we constrain the maximal UHECR energy for a given black hole mass. Among active galaxies, only the most powerful ones, radio galaxies and blazars, are able to accelerate protons to UHE, although acceleration of heavier nuclei is possible in much more abundant lower-power Seyfert galaxies.

Search for the lepton-flavor-violating leptonic B(0)-->mu(+/-)tau(-/+) and B(0)-->e(+/-)tau(-/+).

PubMed

Bornheim, A; Lipeles, E; Pappas, S P; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Rosner, J L; Ryd, A; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Sun, W M; Thayer, J G; Urner, D; Wilksen, T; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Wiss, J; Edwards, K W; Besson, D; Gao, K Y; Gong, D T; Kubota, Y; Li, S Z; Poling, R; Scott, A W; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Arms, K; Gan, K K; Severini, H; Skubic, P; Asner, D M; Dytman, S A; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shibata, E I; Shipsey, I P J; Adams, G S; Chasse, M; Cummings, J P; Danko, I; Napolitano, J; Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dambasuren, E; Dorjkhaidav, O; Menaa, N; Mountain, R; Muramatsu, H; Nandakumar, R; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Mahmood, A H; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M

2004-12-10

We have searched a sample of 9.6 x 10(6) BB events for the lepton-flavor-violating leptonic B decays, B(0)-->mu(+/-)tau(-/+) and B(0)-->e(+/-)tau(-/+). The tau lepton was detected through the decay modes tau-->lnunu(-) , where l=e, mu. There is no indication of a signal, and we obtain the 90% confidence level upper limits B(B(0)-->mu(+/-)tau(-/+))<3.8 x 10(-5) and B(B(0)-->e(+/-)tau(-/+))<1.3 x 10(-4).

Prospect for measuring the CP phase in the $$h\\tau\\tau$$ coupling at the LHC

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

Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi

The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in themore » $$h\\tau\\tau$$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $$\\Theta$$ was proposed for measuring the CP phase in the $$h\\tau\\tau$$ coupling through the $$\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

Prospect for measuring the CP phase in the $$h\\tau\\tau$$ coupling at the LHC

DOE PAGES

Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; ...

2015-04-01

The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in themore » $$h\\tau\\tau$$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $$\\Theta$$ was proposed for measuring the CP phase in the $$h\\tau\\tau$$ coupling through the $$\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease

PubMed Central

Cavallini, Annalisa; Brewerton, Suzanne; Bell, Amanda; Sargent, Samantha; Glover, Sarah; Hardy, Clare; Moore, Roger; Calley, John; Ramachandran, Devaki; Poidinger, Michael; Karran, Eric; Davies, Peter; Hutton, Michael; Szekeres, Philip; Bose, Suchira

2013-01-01

Neurofibrillary tangles, one of the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia. Identifying the kinases involved in the pathological phosphorylation of tau may identify novel targets for AD. We used an unbiased approach to study the effect of 352 human kinases on their ability to phosphorylate tau at epitopes associated with AD. The kinases were overexpressed together with the longest form of human tau in human neuroblastoma cells. Levels of total and phosphorylated tau (epitopes Ser(P)-202, Thr(P)-231, Ser(P)-235, and Ser(P)-396/404) were measured in cell lysates using AlphaScreen assays. GSK3α, GSK3β, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. We further dissected the effects of GSK3α and GSK3β using pharmacological and genetic tools in hTau primary cortical neurons. Pathway analysis of the kinases identified in the screen suggested mechanisms for regulation of total tau levels and tau phosphorylation; for example, kinases that affect total tau levels do so by inhibition or activation of translation. A network fishing approach with the kinase hits identified other key molecules putatively involved in tau phosphorylation pathways, including the G-protein signaling through the Ras family of GTPases (MAPK family) pathway. The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies. PMID:23798682

Structure-based inhibitors of tau aggregation

NASA Astrophysics Data System (ADS)

Seidler, P. M.; Boyer, D. R.; Rodriguez, J. A.; Sawaya, M. R.; Cascio, D.; Murray, K.; Gonen, T.; Eisenberg, D. S.

2018-02-01

Aggregated tau protein is associated with over 20 neurological disorders, which include Alzheimer's disease. Previous work has shown that tau's sequence segments VQIINK and VQIVYK drive its aggregation, but inhibitors based on the structure of the VQIVYK segment only partially inhibit full-length tau aggregation and are ineffective at inhibiting seeding by full-length fibrils. Here we show that the VQIINK segment is the more powerful driver of tau aggregation. Two structures of this segment determined by the cryo-electron microscopy method micro-electron diffraction explain its dominant influence on tau aggregation. Of practical significance, the structures lead to the design of inhibitors that not only inhibit tau aggregation but also inhibit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also raise the possibility that the two VQIINK structures represent amyloid polymorphs of tau that may account for a subset of prion-like strains of tau.

Extragalactic Ultra-High Energy Cosmic-Rays - Part One - Contribution from Hot Spots in Fr-II Radio Galaxies

NASA Astrophysics Data System (ADS)

Rachen, J. P.; Biermann, P. L.

1993-05-01

The hot spots of Fanaroff-Riley class II radio galaxies, considered as working surfaces of highly collimated plasma jets, are proposed to be the dominant sources of the cosmic rays at energies above 1 EeV^a^. We apply the model of first order Fermi acceleration at strong, nonrelativistic shock waves to the hot spot region. The strength of the model has been demonstrated by Biermann & Strittmatter (1987) and by Meisenheimer et al. (1989), who explain their radio-to optical spectra and infer the physical conditions of the radiating plasma. Using synchrotron radiating electrons as a trace, we can calculate the spectrum and the maximum energy of protons accelerated under the same conditions. For simplicity, we disregard heavy nuclei, but their probable role is discussed. The normalization of proton flux injected in extragalactic space is performed by using estimates from Rawlings & Saunders (1991) for the total energy stored in relativistic particles inside the jets and radio galaxy evolution models given by Peacock (1985). We calculate the spectral modifications due to interactions of the protons with the microwave background photons in an evolving universe, following Berezinsky & Grigor'eva (1988). Constraints on the extragalactic magnetic field can be imposed, since it must permit an almost homogeneous filling of the universe with energetic protons. The observed ultra-high energy cosmic ray spectrum is reproduced in slope and flux, limited at high energies by the Greisen-cutoff at about 80 EeV. The requirements on the content of relativistic protons in jets and the constraints to the extragalactic magnetic field are consistent with common estimates. The data beyond the Greisen cutoff for protons may be explained by including heavy nuclei in our model, since they can propagate over cosmological distances up to more than 100 EeV.

Ultra-high resolution computed tomography imaging

DOEpatents

Paulus, Michael J.; Sari-Sarraf, Hamed; Tobin, Jr., Kenneth William; Gleason, Shaun S.; Thomas, Jr., Clarence E.

2002-01-01

A method for ultra-high resolution computed tomography imaging, comprising the steps of: focusing a high energy particle beam, for example x-rays or gamma-rays, onto a target object; acquiring a 2-dimensional projection data set representative of the target object; generating a corrected projection data set by applying a deconvolution algorithm, having an experimentally determined a transfer function, to the 2-dimensional data set; storing the corrected projection data set; incrementally rotating the target object through an angle of approximately 180.degree., and after each the incremental rotation, repeating the radiating, acquiring, generating and storing steps; and, after the rotating step, applying a cone-beam algorithm, for example a modified tomographic reconstruction algorithm, to the corrected projection data sets to generate a 3-dimensional image. The size of the spot focus of the beam is reduced to not greater than approximately 1 micron, and even to not greater than approximately 0.5 microns.

Sources of extracellular tau and its signaling.

PubMed

Avila, Jesús; Simón, Diana; Díaz-Hernández, Miguel; Pintor, Jesús; Hernández, Félix

2014-01-01

The pathology associated with tau protein, tauopathy, has been recently analyzed in different disorders, leading to the suggestion that intracellular and extracellular tau may itself be the principal agent in the transmission and spreading of tauopathies. Tau pathology is based on an increase in the amount of tau, an increase in phosphorylated tau, and/or an increase in aggregated tau. Indeed, phosphorylated tau protein is the main component of tau aggregates, such as the neurofibrillary tangles present in the brain of Alzheimer's disease patients. It has been suggested that intracellular tau could be toxic to neurons in its phosphorylated and/or aggregated form. However, extracellular tau could also damage neurons and since neuronal death is widespread in Alzheimer's disease, mainly among cholinergic neurons, these cells may represent a possible source of extracellular tau. However, other sources of extracellular tau have been proposed that are independent of cell death. In addition, several ways have been proposed for cells to interact with, transmit, and spread extracellular tau, and to transduce signals mediated by this tau. In this work, we will discuss the role of extracellular tau in the spreading of the tau pathology.

Two Novel Tau Antibodies Targeting the 396/404 Region Are Primarily Taken Up by Neurons and Reduce Tau Protein Pathology*

PubMed Central

Gu, Jiaping; Congdon, Erin E.; Sigurdsson, Einar M.

2013-01-01

Aggregated Tau proteins are hallmarks of Alzheimer disease and other tauopathies. Recent studies from our group and others have demonstrated that both active and passive immunizations reduce Tau pathology and prevent cognitive decline in transgenic mice. To determine the efficacy and safety of targeting the prominent 396/404 region, we developed two novel monoclonal antibodies (mAbs) with distinct binding profiles for phospho and non-phospho epitopes. The two mAbs significantly reduced hyperphosphorylated soluble Tau in long term brain slice cultures without apparent toxicity, suggesting the therapeutic importance of targeting the 396/404 region. In mechanistic studies, we found that neurons were the primary cell type that internalized the mAbs, whereas a small amount of mAbs was taken up by microglia cells. Within neurons, the two mAbs were highly colocalized with distinct pathological Tau markers, indicating their affinity toward different stages or forms of pathological Tau. Moreover, the mAbs were largely co-localized with endosomal/lysosomal markers, and partially co-localized with autophagy pathway markers. Additionally, the Fab fragments of the mAbs were able to enter neurons, but unlike the whole antibodies, the fragments were not specifically localized in pathological neurons. In summary, our Tau mAbs were safe and efficient to clear pathological Tau in a brain slice model. Fc-receptor-mediated endocytosis and the endosome/autophagosome/lysosome system are likely to have a critical role in antibody-mediated clearance of Tau pathology. PMID:24089520

Plasma tau in Alzheimer disease.

PubMed

Mattsson, Niklas; Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W; Hansson, Oskar; Blennow, Kaj

2016-10-25

To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18 fluorodeoxyglucose-PET, and cognition. Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ 42 , but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. © 2016 American Academy of Neurology.

Loss of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration and Alzheimer's Disease–Related Tau Phosphorylation Via PAR-1

PubMed Central

Iijima-Ando, Kanae; Sekiya, Michiko; Suzuki, Emiko; Lu, Bingwei; Iijima, Koichi M.

2012-01-01

Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease (AD); however, what pathological conditions trigger tau abnormality in AD is not fully understood. A reduction in the number of mitochondria in the axon has been implicated in AD. In this study, we investigated whether and how loss of axonal mitochondria promotes tau phosphorylation and toxicity in vivo. Using transgenic Drosophila expressing human tau, we found that RNAi–mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD–related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. These results suggest that an increase in tau phosphorylation at Ser262 through PAR-1 contributes to tau-mediated neurodegeneration under a pathological condition in which axonal mitochondria is depleted. Intriguingly, we found that knockdown of milton or Miro alone caused late-onset neurodegeneration in the fly brain, and this neurodegeneration could be suppressed by knockdown of Drosophila tau or PAR-1. Our results suggest that loss of axonal mitochondria may play an important role in tau phosphorylation and toxicity in the pathogenesis of AD. PMID:22952452

Ultrastructural characteristics of tau filaments in tauopathies: immuno-electron microscopic demonstration of tau filaments in tauopathies.

PubMed

Arima, Kunimasa

2006-10-01

The microtubule-associated protein tau aggregates into filaments in the form of neurofibrillary tangles, neuropil threads and argyrophilic grains in neurons, in the form of variable astrocytic tangles in astrocytes and in the form of coiled bodies and argyrophilic threads in oligodendrocytes. These tau filaments may be classified into two types, straight filaments or tubules with 9-18 nm diameters and "twisted ribbons" composed of two parallel aligned components. In the same disease, the fine structure of tau filaments in glial cells roughly resembles that in neurons. In sporadic tauopathies, individual tau filaments show characteristic sizes, shapes and arrangements, and therefore contribute to neuropathologic differential diagnosis. In frontotemporal dementias caused by tau gene mutations, variable filamentous profiles were observed in association with mutation sites and insoluble tau isoforms, including straight filaments or tubules, paired helical filament-like filaments, and twisted ribbons. Pre-embedding immunoelectron microscopic studies were carried out using anti-3-repeat tau and anti-4-repeat tau specific antibodies, RD3 and RD4. Straight tubules in neuronal and astrocytic Pick bodies were immunolabeled by the anti-3-repeat tau antibody. The anti-4-repeat tau antibody recognized abnormal tubules comprising neurofibrillary tangles, coiled bodies and argyrophilic threads in progressive supranuclear palsy (PSP) and corticobasal degeneration. In the pre-embedding immunoelectron microscopic study using the phosphorylated tau AT8 antibody, tuft-shaped astrocytes of PSP were found to be composed of bundles of abnormal tubules in processes and perikarya of protoplasmic astrocytes. In this study, the 3-repeat tau or 4-repeat tau epitope was detected in situ at the ultrastructural level in abnormal tubules in representative pathological lesions in Pick's disease, PSP and corticobasal degeneration.

Study of Ultra-High Energy Cosmic Rays from Extensive Air Showers Radio Emission

NASA Astrophysics Data System (ADS)

Petrov, Igor; Kozlov, Vladimir; Petrov, Zim; Knurenko, Stanislav; Pravdin, Mikhail

The study of cosmic rays with the help of radio detection from extensive air showers may be an alternative to traditional detecting methods, which use a large area array installed with hundreds and thousands of scintillation detectors for charged particles, or the detectors of measuring the emission produced by relativistic particles of EAS in the optical wavelengths. Processes that lead to the emission of electromagnetic radiation are well known and calculations show that the air shower radio emission depends on the processes of development of the electromagnetic cascade, i.e. related with the longitudinal development of the shower, with the magnetic field near sea level etc. In this regard, there is a question to establish the correlation between characteristics of EAS both longitudinal and lateral development and radio emission parameters observed when air shower particles pass through the atmosphere. For this purpose, in Yakutsk, radio array for detecting air shower radio emission was established. The array consists of the antenna field on which crossed antennas are installed; antennas oriented E - W and N - S. Radio emission measurements are conducted at frequency 32 MHz, free from industrial noise. In 2008 - 2013 years, Yakutsk array has measured several seasons of registration of EAS events, including showers with energies above 10 (19) eV. In the course of the data analysis the following results were obtained: a) lateral distribution of the radio signal plotted as a function of distance from the shower axis ; b) a correlation between the amplitude of the radio signal with the energy of the shower, which is determined by measuring the fluxes of charged particles , muons and EAS Cerenkov radiation (energy balance method); c) we made evaluation of the depth of maximum development of the shower using form of radio emission LDF measured in ultra-high energy showers; g) a comparison of the Yakutsk array data with data from other arrays.

The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases.

PubMed

Vermeiren, Céline; Motte, Philippe; Viot, Delphine; Mairet-Coello, Georges; Courade, Jean-Philippe; Citron, Martin; Mercier, Joël; Hannestad, Jonas; Gillard, Michel

2018-02-01

Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in the clinic. Although results obtained in Alzheimer's disease patients are compelling, discrimination of tracer uptake in healthy individuals and patients with supranuclear palsy (PSP) is less clear as there is substantial overlap of signal in multiple brain regions. Moreover, accurate quantification of [ 18 F]AV-1451 uptake in Alzheimer's disease may not be possible. The aim of the present study was to characterize the in vitro binding of AV-1451 to understand and identify potential off-target binding that could explain the poor discrimination observed in PSP patients. [ 3 H]AV-1451 and AV-1451 were characterized in in vitro binding assays using recombinant and native proteins/tissues from postmortem samples of controls and Alzheimer's disease and PSP patients. [ 3 H]AV-1451 binds to multiple sites with nanomolar affinities in brain homogenates and to tau fibrils isolated from Alzheimer's disease or PSP patients. [ 3 H]AV-1451 also binds with similarly high affinities in brain homogenates devoid of tau pathology. This unexpected binding was demonstrated to be because of nanomolar affinities of [ 3 H]AV-1451 for monoamine oxidase A and B enzymes. High affinity of AV-1451 for monoamine oxidase proteins may limit its utility as a tau PET tracer in PSP and Alzheimer's disease because of high levels of monoamine oxidase expression in brain regions also affected by tau deposition, especially if monoamine oxidase levels change over time or with a treatment intervention. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

PubMed Central

Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

2015-01-01

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

PubMed

Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing

2015-03-01

A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure-activity relationship of cyanine tau aggregation inhibitors

PubMed Central

Chang, Edward; Congdon, Erin E.; Honson, Nicolette S.; Duff, Karen E.; Kuret, Jeff

2009-01-01

A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3’-diethyl-9-methylthiacarbocyanine iodide (compound 11), retained submicromolar potency and had calculated physical properties consistent with blood-brain barrier and cell membrane penetration. Exposure of organotypic slices prepared from JNPL3 transgenic mice (which express human tau harboring the aggregation prone P301L tauopathy mutation) to compound 11 for one week revealed a biphasic dose response relationship. Low nanomolar concentrations decreased insoluble tau aggregates to half those observed in slices treated with vehicle alone. In contrast, high concentrations (≥300 nM) augmented tau aggregation and produced abnormalities in tissue tubulin levels. These data suggest that certain symmetrical carbocyanine dyes can modulate tau aggregation in the slice biological model at concentrations well below those associated with toxicity. PMID:19432420

Compact high-pulse-energy passively Q-switched Nd:YLF laser with an ultra-low-magnification unstable resonator: application for efficient optical parametric oscillator.

PubMed

Cho, C Y; Huang, Y P; Huang, Y J; Chen, Y C; Su, K W; Chen, Y F

2013-01-28

We exploit an ultra-low-magnification unstable resonator to develop a high-pulse-energy side-pumped passively Q-switched Nd:YLF/Cr⁴⁺:YAG laser with improving beam quality. A wedged laser crystal is employed in the cavity to control the emissions at 1047 nm and 1053 nm independently through the cavity alignment. The pulse energies at 1047 nm and 1053 nm are found to be 19 mJ and 23 mJ, respectively. The peak powers for both wavelengths are higher than 2 MW. Furthermore, the developed Nd:YLF lasers are employed to pump a monolithic optical parametric oscillator for confirming the applicability in nonlinear wavelength conversions.

Organic field effect transistor with ultra high amplification

NASA Astrophysics Data System (ADS)

Torricelli, Fabrizio

2016-09-01

High-gain transistors are essential for the large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel-length modulation. Here we show organic transistors fabricated on plastic foils enabling unipolar amplifiers with ultra-gain. The proposed approach is general and opens up new opportunities for ultra-large signal amplification in organic circuits and sensors.

Formal thought disorder in people at ultra-high risk of psychosis

PubMed Central

Weinstein, Sara; Stahl, Daniel; Day, Fern; Valmaggia, Lucia; Rutigliano, Grazia; De Micheli, Andrea; Fusar-Poli, Paolo; McGuire, Philip

2017-01-01

Background Formal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear. Aims Examine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis. Method The Thought and Language Index (TLI) was used to assess 24 ultra-high-risk participants, 16 people with first-episode psychosis and 13 healthy controls. Ultra-high-risk individuals were followed up for a mean duration of 7 years (s.d.=1.5) to determine the relationship between formal thought disorder at baseline and transition to psychosis. Results TLI scores were significantly greater in the ultra-high-risk group compared with the healthy control group (effect size (ES)=1.2), but lower than in people with first-episode psychosis (ES=0.8). Total and negative TLI scores were higher in ultra-high-risk individuals who developed psychosis, but this was not significant. Combining negative TLI scores with attenuated psychotic symptoms and basic symptoms predicted transition to psychosis (P=0.04; ES=1.04). Conclusions TLI is beneficial in evaluating formal thought disorder in ultra-high-risk participants, and complements existing instruments for the evaluation of psychopathology in this group. Declaration of interests None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28713586

Spatially and momentum resolved energy electron loss spectra from an ultra-thin PrNiO{sub 3} layer

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

Kinyanjui, M. K., E-mail: michael.kinyanjui@uni-ulm.de; Kaiser, U.; Benner, G.

2015-05-18

We present an experimental approach which allows for the acquisition of spectra from ultra-thin films at high spatial, momentum, and energy resolutions. Spatially and momentum (q) resolved electron energy loss spectra have been obtained from a 12 nm ultra-thin PrNiO{sub 3} layer using a nano-beam electron diffraction based approach which enabled the acquisition of momentum resolved spectra from individual, differently oriented nano-domains and at different positions of the PrNiO{sub 3} thin layer. The spatial and wavelength dependence of the spectral excitations are obtained and characterized after the analysis of the experimental spectra using calculated dielectric and energy loss functions. The presentedmore » approach makes a contribution towards obtaining momentum-resolved spectra from nanostructures, thin film, heterostructures, surfaces, and interfaces.« less

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations.

PubMed

Matsui, S; Mori, Y; Nonaka, T; Hattori, T; Kasamatsu, Y; Haraguchi, D; Watanabe, Y; Uchiyama, K; Ishikawa, M

2016-05-01

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films and Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.

Measurement of ultra-low ion energy of decelerated ion beam using a deflecting electric field

NASA Astrophysics Data System (ADS)

Thopan, P.; Suwannakachorn, D.; Tippawan, U.; Yu, L. D.

2015-12-01

In investigation on ultra-low-energy ion bombardment effect on DNA, an ion beam deceleration lens was developed for high-quality ultra-low-energy ion beam. Measurement of the ion energy after deceleration was necessary to confirm the ion beam really decelerated as theoretically predicted. In contrast to conventional methods, this work used a simple deflecting electrostatic field after the deceleration lens to bend the ion beam. The beam bending distance depended on the ion energy and was described and simulated. A system for the measurement of the ion beam energy was constructed. It consisted of a pair of parallel electrode plates to generate the deflecting electrical field, a copper rod measurement piece to detect ion beam current, a vernier caliper to mark the beam position, a stepping motor to translate the measurement rod, and a webcam-camera to read the beam bending distance. The entire system was installed after the ion-beam deceleration lens inside the large chamber of the bioengineering vertical ion beam line. Moving the measurement rod across the decelerated ion beam enabled to obtain beam profiles, from which the beam bending distance could be known and the ion beam energy could be calculated. The measurement results were in good agreement with theoretical and simulated results.

Study of dispersion of mass distribution of ultra-high energy cosmic rays using a surface array of muon and electromagnetic detectors

NASA Astrophysics Data System (ADS)

Vícha, Jakub; Trávníček, Petr; Nosek, Dalibor; Ebr, Jan

2015-09-01

We consider a hypothetical observatory of ultra-high energy cosmic rays consisting of two surface detector arrays that measure independently electromagnetic and muon signals induced by air showers. Using the constant intensity cut method, sets of events ordered according to each of both signal sizes are compared giving the number of matched events. Based on its dependence on the zenith angle, a parameter sensitive to the dispersion of the distribution of the logarithmic mass of cosmic rays is introduced. The results obtained using two post-LHC models of hadronic interactions are very similar and indicate a weak dependence on details of these interactions.

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

PubMed

Mielke, Michelle M; Hagen, Clinton E; Xu, Jing; Chai, Xiyun; Vemuri, Prashanthi; Lowe, Val J; Airey, David C; Knopman, David S; Roberts, Rosebud O; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Dage, Jeffrey L

2018-04-04

We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. Copyright © 2018. Published by Elsevier Inc.

Future ultra-speed tube-flight

NASA Astrophysics Data System (ADS)

Salter, Robert M.

1994-05-01

Future long-link, ultra-speed, surface transport systems will require electromagnetically (EM) driven and restrained vehicles operating under reduced-atmosphere in very straight tubes. Such tube-flight trains will be safe, energy conservative, pollution-free, and in a protected environment. Hypersonic (and even hyperballistic) speeds are theoretically achievable. Ultimate system choices will represent tradeoffs between amoritized capital costs (ACC) and operating costs. For example, long coasting links might employ aerodynamic lift coupled with EM restraint and drag make-up. Optimized, combined EM lift, and thrust vectors could reduce energy costs but at increased ACC. (Repulsive levitation can produce lift-over-drag l/d ratios a decade greater than aerodynamic), Alternatively, vehicle-emanated, induced-mirror fields in a conducting (aluminum sheet) road bed could reduce ACC but at substantial energy costs. Ultra-speed tube flight will demand fast-acting, high-precision sensors and computerized magnetic shimming. This same control system can maintain a magnetic 'guide way' invariant in inertial space with inertial detectors imbedded in tube structures to sense and correct for earth tremors. Ultra-speed tube flight can complete with aircraft for transit time and can provide even greater passenger convenience by single-model connections with local subways and feeder lines. Although cargo transport generally will not need to be performed at ultra speeds, such speeds may well be desirable for high throughput to optimize channel costs. Thus, a large and expensive pipeline might be replaced with small EM-driven pallets at high speeds.

Future ultra-speed tube-flight

NASA Technical Reports Server (NTRS)

Salter, Robert M.

1994-01-01

Future long-link, ultra-speed, surface transport systems will require electromagnetically (EM) driven and restrained vehicles operating under reduced-atmosphere in very straight tubes. Such tube-flight trains will be safe, energy conservative, pollution-free, and in a protected environment. Hypersonic (and even hyperballistic) speeds are theoretically achievable. Ultimate system choices will represent tradeoffs between amoritized capital costs (ACC) and operating costs. For example, long coasting links might employ aerodynamic lift coupled with EM restraint and drag make-up. Optimized, combined EM lift, and thrust vectors could reduce energy costs but at increased ACC. (Repulsive levitation can produce lift-over-drag l/d ratios a decade greater than aerodynamic), Alternatively, vehicle-emanated, induced-mirror fields in a conducting (aluminum sheet) road bed could reduce ACC but at substantial energy costs. Ultra-speed tube flight will demand fast-acting, high-precision sensors and computerized magnetic shimming. This same control system can maintain a magnetic 'guide way' invariant in inertial space with inertial detectors imbedded in tube structures to sense and correct for earth tremors. Ultra-speed tube flight can complete with aircraft for transit time and can provide even greater passenger convenience by single-model connections with local subways and feeder lines. Although cargo transport generally will not need to be performed at ultra speeds, such speeds may well be desirable for high throughput to optimize channel costs. Thus, a large and expensive pipeline might be replaced with small EM-driven pallets at high speeds.

INVESTIGATING PLANET FORMATION IN CIRCUMSTELLAR DISKS: CARMA OBSERVATIONS OF RY Tau AND DG Tau

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

Isella, Andrea; Carpenter, John M.; Sargent, Anneila I., E-mail: isella@astro.caltech.ed

2010-05-10

We present CARMA observations of the thermal dust emission from the circumstellar disks around the young stars RY Tau and DG Tau at wavelengths of 1.3 mm and 2.8 mm. The angular resolution of the maps is as high as 0.''15, or 20 AU at the distance of the Taurus cloud, which is a factor of 2 higher than has been achieved to date at these wavelengths. The unprecedented detail of the resulting disk images enables us to address three important questions related to the formation of planets. (1) What is the radial distribution of the circumstellar dust? (2) Doesmore » the dust emission show any indication of gaps that might signify the presence of (proto-)planets? (3) Do the dust properties depend on the orbital radius? We find that modeling the disk surface density in terms of either a classical power law or the similarity solution for viscous disk evolution reproduces the observations well. Both models constrain the surface density between 15 and 50 AU to within 30% for a given dust opacity. Outside this range, the densities inferred from the two models differ by almost an order of magnitude. The 1.3 mm image from RY Tau shows two peaks separated by 0.''2 with a decline in the dust emission toward the stellar position, which is significant at about 2{sigma}-4{sigma}. For both RY Tau and DG Tau, the dust emission at radii larger than 15 AU displays no significant deviation from an unperturbed viscous disk model. In particular, no radial gaps in the dust distribution are detected. Under reasonable assumptions, we exclude the presence of planets more massive than 5 M{sub J} orbiting either star at distances between about 10 and 60 AU, unless such a planet is so young that there has been insufficient time to open a gap in the disk surface density. The radial variation of the dust opacity slope, {beta}, was investigated by comparing the 1.3 mm and 2.8 mm observations. We find mean values of {beta} of 0.5 and 0.7 for DG Tau and RY Tau, respectively. Variations in {beta

Changes in tau phosphorylation in hibernating rodents.

PubMed

León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; Defelipe, Javier; Avila, Jesús

2013-07-01

Tau is a cytoskeletal protein present mainly in the neurons of vertebrates. By comparing the sequence of tau molecule among different vertebrates, it was found that the variability of the N-terminal sequence in tau protein is higher than that of the C-terminal region. The N-terminal region is involved mainly in the binding of tau to cellular membranes, whereas the C-terminal region of the tau molecule contains the microtubule-binding sites. We have compared the sequence of Syrian hamster tau with the sequences of other hibernating and nonhibernating rodents and investigated how differences in the N-terminal region of tau could affect the phosphorylation level and tau binding to cell membranes. We also describe a change, in tau phosphorylation, on a casein kinase 1 (ck1)-dependent site that is found only in hibernating rodents. This ck1 site seems to play an important role in the regulation of tau binding to membranes. Copyright © 2013 Wiley Periodicals, Inc.

Study of Ultra-High Energy Cosmic Ray composition using Telescope Array's Middle Drum detector and surface array in hybrid mode

NASA Astrophysics Data System (ADS)

Abbasi, R. U.; Abe, M.; Abu-Zayyad, T.; Allen, M.; Anderson, R.; Azuma, R.; Barcikowski, E.; Belz, J. W.; Bergman, D. R.; Blake, S. A.; Cady, R.; Chae, M. J.; Cheon, B. G.; Chiba, J.; Chikawa, M.; Cho, W. R.; Fujii, T.; Fukushima, M.; Goto, T.; Hanlon, W.; Hayashi, Y.; Hayashida, N.; Hibino, K.; Honda, K.; Ikeda, D.; Inoue, N.; Ishii, T.; Ishimori, R.; Ito, H.; Ivanov, D.; Jui, C. C. H.; Kadota, K.; Kakimoto, F.; Kalashev, O.; Kasahara, K.; Kawai, H.; Kawakami, S.; Kawana, S.; Kawata, K.; Kido, E.; Kim, H. B.; Kim, J. H.; Kim, J. H.; Kitamura, S.; Kitamura, Y.; Kuzmin, V.; Kwon, Y. J.; Lan, J.; Lim, S. I.; Lundquist, J. P.; Machida, K.; Martens, K.; Matsuda, T.; Matsuyama, T.; Matthews, J. N.; Minamino, M.; Mukai, Y.; Myers, I.; Nagasawa, K.; Nagataki, S.; Nakamura, T.; Nonaka, T.; Nozato, A.; Ogio, S.; Ogura, J.; Ohnishi, M.; Ohoka, H.; Oki, K.; Okuda, T.; Ono, M.; Oshima, A.; Ozawa, S.; Park, I. H.; Pshirkov, M. S.; Rodriguez, D. C.; Rubtsov, G.; Ryu, D.; Sagawa, H.; Sakurai, N.; Sampson, A. L.; Scott, L. M.; Shah, P. D.; Shibata, F.; Shibata, T.; Shimodaira, H.; Shin, B. K.; Shin, H. S.; Smith, J. D.; Sokolsky, P.; Springer, R. W.; Stokes, B. T.; Stratton, S. R.; Stroman, T.; Suzawa, T.; Takamura, M.; Takeda, M.; Takeishi, R.; Taketa, A.; Takita, M.; Tameda, Y.; Tanaka, H.; Tanaka, K.; Tanaka, M.; Thomas, S. B.; Thomson, G. B.; Tinyakov, P.; Tkachev, I.; Tokuno, H.; Tomida, T.; Troitsky, S.; Tsunesada, Y.; Tsutsumi, K.; Uchihori, Y.; Udo, S.; Urban, F.; Vasiloff, G.; Wong, T.; Yamane, R.; Yamaoka, H.; Yamazaki, K.; Yang, J.; Yashiro, K.; Yoneda, Y.; Yoshida, S.; Yoshii, H.; Zollinger, R.; Zundel, Z.

2015-04-01

Previous measurements of the composition of Ultra-High Energy Cosmic Rays (UHECRs) made by the High Resolution Fly's Eye (HiRes) and Pierre Auger Observatory (PAO) are seemingly contradictory, but utilize different detection methods, as HiRes was a stereo detector and PAO is a hybrid detector. The five year Telescope Array (TA) Middle Drum hybrid composition measurement is similar in some, but not all, respects in methodology to PAO, and good agreement is evident between data and a light, largely protonic, composition when comparing the measurements to predictions obtained with the QGSJetII-03 and QGSJet-01c models. These models are also in agreement with previous HiRes stereo measurements, confirming the equivalence of the stereo and hybrid methods. The data is incompatible with a pure iron composition, for all models examined, over the available range of energies. The elongation rate and mean values of Xmax are in good agreement with Pierre Auger Observatory data. This analysis is presented using two methods: data cuts using simple geometrical variables and a new pattern recognition technique.

Fusion: ultra-high-speed and IR image sensors

NASA Astrophysics Data System (ADS)

Etoh, T. Goji; Dao, V. T. S.; Nguyen, Quang A.; Kimata, M.

2015-08-01

Most targets of ultra-high-speed video cameras operating at more than 1 Mfps, such as combustion, crack propagation, collision, plasma, spark discharge, an air bag at a car accident and a tire under a sudden brake, generate sudden heat. Researchers in these fields require tools to measure the high-speed motion and heat simultaneously. Ultra-high frame rate imaging is achieved by an in-situ storage image sensor. Each pixel of the sensor is equipped with multiple memory elements to record a series of image signals simultaneously at all pixels. Image signals stored in each pixel are read out after an image capturing operation. In 2002, we developed an in-situ storage image sensor operating at 1 Mfps 1). However, the fill factor of the sensor was only 15% due to a light shield covering the wide in-situ storage area. Therefore, in 2011, we developed a backside illuminated (BSI) in-situ storage image sensor to increase the sensitivity with 100% fill factor and a very high quantum efficiency 2). The sensor also achieved a much higher frame rate,16.7 Mfps, thanks to the wiring on the front side with more freedom 3). The BSI structure has another advantage that it has less difficulties in attaching an additional layer on the backside, such as scintillators. This paper proposes development of an ultra-high-speed IR image sensor in combination of advanced nano-technologies for IR imaging and the in-situ storage technology for ultra-highspeed imaging with discussion on issues in the integration.

Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

PubMed Central

Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

2013-01-01

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations

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

Matsui, S., E-mail: smatsui@gpi.ac.jp; Mori, Y.; Nonaka, T.

2016-05-15

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films andmore » Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.« less

Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.

PubMed

La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M; Ayakta, Nagehan; Baker, Suzanne L; Bourakova, Viktoriya; Boxer, Adam L; Cha, Jungho; Karydas, Anna; Jerome, Gina; Maass, Anne; Mensing, Ashley; Miller, Zachary A; O'Neil, James P; Pham, Julie; Rosen, Howard J; Tsai, Richard; Visani, Adrienne V; Miller, Bruce L; Jagust, William J; Rabinovici, Gil D

2018-01-23

To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([ 18 F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ 42 , total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. [ 18 F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [ 18 F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau ( r = 0.75 vs 0.57 for t-tau and -0.49 for Aβ 42 ). When restricted to Aβ-positive patients with AD, [ 18 F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ 42 ( r = 0.02). On voxelwise analysis, [ 18 F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [ 18 F]AV1451-PET, but not CSF biomarkers. [ 18 F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. This study provides Class III evidence that, in a clinical sample of patients with a variety

Four-Year Follow-up of Cognitive Behavioral Therapy in Persons at Ultra-High Risk for Developing Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

PubMed

Ising, Helga K; Kraan, Tamar C; Rietdijk, Judith; Dragt, Sara; Klaassen, Rianne M C; Boonstra, Nynke; Nieman, Dorien H; Willebrands-Mendrik, Monique; van den Berg, David P G; Linszen, Don H; Wunderink, Lex; Veling, Wim; Smit, Filip; van der Gaag, Mark

2016-09-01

Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline. The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated. The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up. CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases. The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (http://controlled-trials.com/ISRCTN21353122/gaag). © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights

18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

PubMed Central

Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet

2016-01-01

Abstract Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo. However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with 18F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer’s disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited 18F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was 18F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

Ultra-High Gradient S-band Linac for Laboratory and Industrial Applications

NASA Astrophysics Data System (ADS)

Faillace, L.; Agustsson, R.; Dolgashev, V.; Frigola, P.; Murokh, A.; Rosenzweig, J.; Yakimenko, V.

2010-11-01

A strong demand for high gradient structures arises from the limited real estate available for linear accelerators. RadiaBeam Technologies is developing a Doubled Energy Compact Accelerator (DECA) structure: an S-band standing wave electron linac designed to operate at accelerating gradients of up to 50 MV/m. In this paper, we present the radio-frequency design of the DECA S-band accelerating structure, operating at 2.856 GHz in the π-mode. The structure design is heavily influenced by NLC collaboration experience with ultra high gradient X-band structures; S-band, however, is chosen to take advantage of commonly available high power S-band klystrons.

Integrating high levels of variable renewable energy into electric power systems

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

Kroposki, Benjamin

As more variable renewable energy (VRE) such as wind and solar are integrated into electric power systems, technical challenges arise from the need to maintain the balance between load and generation at all timescales. This paper examines the challenges with integrating ultra-high levels of VRE into electric power system, reviews a range of solutions to these challenges, and provides a description of several examples of ultra-high VRE systems that are in operation today.

Integrating high levels of variable renewable energy into electric power systems

DOE PAGES

Kroposki, Benjamin

2017-11-17

As more variable renewable energy (VRE) such as wind and solar are integrated into electric power systems, technical challenges arise from the need to maintain the balance between load and generation at all timescales. This paper examines the challenges with integrating ultra-high levels of VRE into electric power system, reviews a range of solutions to these challenges, and provides a description of several examples of ultra-high VRE systems that are in operation today.

Treatment-as-usual (TAU) is anything but usual: a meta-analysis of CBT versus TAU for anxiety and depression.

PubMed

Watts, Sarah E; Turnell, Adrienne; Kladnitski, Natalie; Newby, Jill M; Andrews, Gavin

2015-04-01

There were three aims of this study, the first was to examine the efficacy of CBT versus treatment-as-usual (TAU) in the treatment of anxiety and depressive disorders, the second was to examine how TAU is defined in TAU control groups for those disorders, and the third was to explore whether the type of TAU condition influences the estimate of effects of CBT. A systematic search of Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL was conducted. 48 studies of CBT for depressive or anxiety disorders (n=6926) that specified that their control group received TAU were identified. Most (n=45/48) provided an explanation of the TAU group however there was significant heterogeneity amongst TAU conditions. The meta-analysis showed medium effects favoring CBT over TAU for both anxiety (g=0.69, 95% CI 0.47-0.92, p<0.001, n=1318) and depression (g=0.70, 95% CI 0.49-0.90, p<0.001, n=5054), with differential effects observed across TAU conditions. CBT is superior to TAU and the size of the effect of CBT compared to TAU depends on the nature of the TAU condition. The term TAU is used in different ways and should be more precisely described. The four key details to be reported can be thought of as "who, what, how many, and any additional treatments?" Copyright © 2014 Elsevier B.V. All rights reserved.

Observation of Upsilon(3S)-->tau+tau- and tests of lepton universality in Upsilon decays.

PubMed

Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Severini, H; Dytman, S A; Love, W; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Blusk, S; Butt, J; Horwitz, N; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Patel, R; Potlia, V; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R

2007-02-02

Using data collected with the CLEO III detector at the CESR e+e- collider, we report on a first observation of the decay Upsilon(3S)-->tau+tau-, and precisely measure the ratio of branching fractions of Upsilon(nS), n=1, 2, 3, to tau+tau- and mu+mu- final states, finding agreement with expectations from lepton universality. We derive absolute branching fractions for these decays, and also set a limit on the influence of a low mass CP-odd Higgs boson in the decay of the Upsilon(1S).

Application of the discrete generalized multigroup method to ultra-fine energy mesh in infinite medium calculations

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

Gibson, N. A.; Forget, B.

2012-07-01

The Discrete Generalized Multigroup (DGM) method uses discrete Legendre orthogonal polynomials to expand the energy dependence of the multigroup neutron transport equation. This allows a solution on a fine energy mesh to be approximated for a cost comparable to a solution on a coarse energy mesh. The DGM method is applied to an ultra-fine energy mesh (14,767 groups) to avoid using self-shielding methodologies without introducing the cost usually associated with such energy discretization. Results show DGM to converge to the reference ultra-fine solution after a small number of recondensation steps for multiple infinite medium compositions. (authors)

A study of ultra high energy radiation associated with Hercules X-1

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

Biller, Steven Douglas

1992-01-01

Data from the CYGNUS experiment has been used to examine ultra high energy (UHE) radiation associated with the X-ray binary star system Hercules X-1. A search for both pulsed, and unpulsed emission over time scales ranging from minutes to years has failed to yield a result of comparable significance to that of the previously published observation of July 24, 1986. A reassessment of this result in light of the number of hypotheses that have been examined for Hercules X-1 yields a probability estimate of 0.44% that the data is consistent with background fluctuations. If the number of independent source hypothesesmore » is also accounted for, an overall chance probability of 1.8% is assessed for the observations of the CYGNUS experiment. The extensive air showers corresponding to the episode of July 24, 1986 contain a substantial muon content, in contradiction with traditional predictions for primary gamma-rays. No satisfactory theory has yet been put forward to explain this phenomenon. A further analysis of shower characteristics for events associated with this episode indicates a steeper radial dependence of the showerfront timing width at a chance probability level of 0.16%. This property might be explained by a model that invokes a forward-peaked and/or a deeply interacting component of the hadronic interaction in the atmosphere. The potential importance of UHE observations of Hercules X-1 is great. however the evidence is not yet compelling. Further observations will be necessary, to confirm the potential properties of associated UHE radiation.« less

A measurement of the tau Michel parameters at SLD

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

Quigley, James A.

1997-05-01

This thesis presents a measurement of the tau Michel parameters. This measurement utilizes the highly polarized SLC electron beam to extract these quantities directly from the measured tau decay spectra using the 1993--95 SLD sample of 4,528 tau pair events. The results are ρ e = 0.71 ± 0.14 ± 0.05, ζ e = 1.16 ± 0.52 ± 0.06, and (ζδ) e = 0.85 ± 0.43 ± 0.08 for tau decays to electrons and ρ μ = 0.54 ± 0.28 μ 0.14, η μ = -0.59 ± 0.82 ± 0.45, ζsup>μ = 0.75 ± 0.50 ± 0.14, and (ζδ) μmore » = 0.82 ± 0.32 ± 0.07 for tau decays to muons. Combining all leptonic tau decays gives ρ = 0.72 ± 0.09 ± 0.03, ζ = 1.05 ± 0.35 ± 0.04, and ζδ = 0.88 ± 0.27 ± 0.04. These results agree well with the current world average and the Standard Model.« less

Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

PubMed

Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Marette, André; Planel, Emmanuel

2017-10-03

Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD. We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions. We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results. In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies. Copyright © 2017. Published by Elsevier Inc.

Imbalance of Hsp70 family variants fosters tau accumulation.

PubMed

Jinwal, Umesh K; Akoury, Elias; Abisambra, Jose F; O'Leary, John C; Thompson, Andrea D; Blair, Laura J; Jin, Ying; Bacon, Justin; Nordhues, Bryce A; Cockman, Matthew; Zhang, Juan; Li, Pengfei; Zhang, Bo; Borysov, Sergiy; Uversky, Vladimir N; Biernat, Jacek; Mandelkow, Eckhard; Gestwicki, Jason E; Zweckstetter, Markus; Dickey, Chad A

2013-04-01

Dysfunctional tau accumulation is a major contributing factor in tauopathies, and the heat-shock protein 70 (Hsp70) seems to play an important role in this accumulation. Several reports suggest that Hsp70 proteins can cause tau degradation to be accelerated or slowed, but how these opposing activities are controlled is unclear. Here we demonstrate that highly homologous variants in the Hsp70 family can have opposing effects on tau clearance kinetics. When overexpressed in a tetracycline (Tet)-based protein chase model, constitutive heat shock cognate 70 (Hsc70) and inducible Hsp72 slowed or accelerated tau clearance, respectively. Tau synergized with Hsc70, but not Hsp72, to promote microtubule assembly at nearly twice the rate of either Hsp70 homologue in reconstituted, ATP-regenerating Xenopus extracts supplemented with rhodamine-labeled tubulin and human recombinant Hsp72 and Hsc70. Nuclear magnetic resonance spectroscopy with human recombinant protein revealed that Hsp72 had greater affinity for tau than Hsc70 (I/I0 ratio difference of 0.3), but Hsc70 was 30 times more abundant than Hsp72 in human and mouse brain tissue. This indicates that the predominant Hsp70 variant in the brain is Hsc70, suggesting that the brain environment primarily supports slower tau clearance. Despite its capacity to clear tau, Hsp72 was not induced in the Alzheimer's disease brain, suggesting a mechanism for age-associated onset of the disease. Through the use of chimeras that blended the domains of Hsp72 and Hsc70, we determined that the reason for these differences between Hsc70 and Hsp72 with regard to tau clearance kinetics lies within their C-terminal domains, which are essential for their interactions with substrates and cochaperones. Hsp72 but not Hsc70 in the presence of tau was able to recruit the cochaperone ubiquitin ligase CHIP, which is known to facilitate the ubiquitination of tau, describing a possible mechanism of how the C-termini of these homologous Hsp70 variants

[Extreme (complicated, ultra-high) refractive errors: terminological misconceptions!?

PubMed

Avetisov, S E

2018-01-01

The article reviews development mechanisms of different refractive errors accompanied by marked defocus of light rays reaching the retina. Terminology used for such ametropias includes terms extreme, ultra-high and complicated. Justification of their usage for primary ametropias, whose symptom complex is based on changes in axial eye length, is an ongoing discussion. To comply with thesaurus definitions of 'diagnosis' and 'pathogenesis', to characterize refractive and anatomical-functional disorders in patients with primary ametropias it is proposed to use the terms 'hyperaxial and hypoaxial syndromes' with elaboration of specific symptoms instead of such expressions as extreme (ultra-high) myopia and hypermetropia.

Reconstruction of hadronic decay products of tau leptons with the ATLAS experiment

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2016-05-25

This document presents a new method of reconstructing the individual charged and neutral hadrons in tau decays with the ATLAS detector. The reconstructed hadrons are used to classify the decay mode and to calculate the visible four-momentum of reconstructed tau candidates, significantly improving the resolution with respect to the calibration in the existing tau reconstruction. The performance of the reconstruction algorithm is optimised and evaluated using simulation and validated using samples of Z → ττ and Z(→ μμ)+jets events selected from proton–proton collisions at a centre-of-mass energy √s = 8 TeV, corresponding to an integrated luminosity of 5 fb -1.

Reconstruction of hadronic decay products of tau leptons with the ATLAS experiment.

PubMed

Aad, G; Abbott, B; Abdallah, J; Abdinov, O; Aben, R; Abolins, M; AbouZeid, O S; Abramowicz, H; Abreu, H; Abreu, R; Abulaiti, Y; Acharya, B S; Adamczyk, L; Adams, D L; Adelman, J; Adomeit, S; Adye, T; Affolder, A A; Agatonovic-Jovin, T; Agricola, J; Aguilar-Saavedra, J A; Ahlen, S P; Ahmadov, F; Aielli, G; Akerstedt, H; Åkesson, T P A; Akimov, A V; Alberghi, G L; Albert, J; Albrand, S; Alconada Verzini, M J; Aleksa, M; Aleksandrov, I N; Alexa, C; Alexander, G; Alexopoulos, T; Alhroob, M; Alimonti, G; Alio, L; Alison, J; Alkire, S P; Allbrooke, B M M; Allport, P P; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Altheimer, A; Alvarez Gonzalez, B; Álvarez Piqueras, D; Alviggi, M G; Amadio, B T; Amako, K; Amaral Coutinho, Y; Amelung, C; Amidei, D; Amor Dos Santos, S P; Amorim, A; Amoroso, S; Amram, N; Amundsen, G; Anastopoulos, C; Ancu, L S; Andari, N; Andeen, T; Anders, C F; Anders, G; Anders, J K; Anderson, K J; Andreazza, A; Andrei, V; Angelidakis, S; Angelozzi, I; Anger, P; Angerami, A; Anghinolfi, F; Anisenkov, A V; Anjos, N; Annovi, A; Antonelli, M; Antonov, A; Antos, J; Anulli, F; Aoki, M; Aperio Bella, L; Arabidze, G; Arai, Y; Araque, J P; Arce, A T H; Arduh, F A; Arguin, J-F; Argyropoulos, S; Arik, M; Armbruster, A J; Arnaez, O; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Artz, S; Asai, S; Asbah, N; Ashkenazi, A; Åsman, B; Asquith, L; Assamagan, K; Astalos, R; Atkinson, M; Atlay, N B; Augsten, K; Aurousseau, M; Avolio, G; Axen, B; Ayoub, M K; Azuelos, G; Baak, M A; Baas, A E; Baca, M J; Bachacou, H; Bachas, K; Backes, M; Backhaus, M; Bagiacchi, P; Bagnaia, P; Bai, Y; Bain, T; Baines, J T; Baker, O K; Baldin, E M; Balek, P; Balestri, T; Balli, F; Balunas, W K; Banas, E; Banerjee, Sw; Bannoura, A A E; Barak, L; Barberio, E L; Barberis, D; Barbero, M; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnes, S L; Barnett, B M; Barnett, R M; Barnovska, Z; Baroncelli, A; Barone, G; Barr, A J; Barreiro, F; Barreiro Guimarães da Costa, J; Bartoldus, R; Barton, A E; Bartos, P; Basalaev, A; Bassalat, A; Basye, A; Bates, R L; Batista, S J; Batley, J R; Battaglia, M; Bauce, M; Bauer, F; Bawa, H S; Beacham, J B; Beattie, M D; Beau, T; Beauchemin, P H; Beccherle, R; Bechtle, P; Beck, H P; Becker, K; Becker, M; Beckingham, M; Becot, C; Beddall, A J; Beddall, A; Bednyakov, V A; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, J K; Belanger-Champagne, C; Bell, W H; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Benary, O; Benchekroun, D; Bender, M; Bendtz, K; Benekos, N; Benhammou, Y; Benhar Noccioli, E; Benitez Garcia, J A; Benjamin, D P; Bensinger, J R; Bentvelsen, S; Beresford, L; Beretta, M; Berge, D; Bergeaas Kuutmann, E; Berger, N; Berghaus, F; Beringer, J; Bernard, C; Bernard, N R; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertsche, C; Bertsche, D; Besana, M I; Besjes, G J; Bessidskaia Bylund, O; Bessner, M; Besson, N; Betancourt, C; Bethke, S; Bevan, A J; Bhimji, W; Bianchi, R M; Bianchini, L; Bianco, M; Biebel, O; Biedermann, D; Biesuz, N V; Biglietti, M; Bilbao De Mendizabal, J; Bilokon, H; Bindi, M; Binet, S; Bingul, A; Bini, C; Biondi, S; Bjergaard, D M; Black, C W; Black, J E; Black, K M; Blackburn, D; Blair, R E; Blanchard, J-B; Blanco, J E; Blazek, T; Bloch, I; Blocker, C; Blum, W; Blumenschein, U; Blunier, S; Bobbink, G J; Bobrovnikov, V S; Bocchetta, S S; Bocci, A; Bock, C; Boehler, M; Bogaerts, J A; Bogavac, D; Bogdanchikov, A G; Bohm, C; Boisvert, V; Bold, T; Boldea, V; Boldyrev, A S; Bomben, M; Bona, M; Boonekamp, M; Borisov, A; Borissov, G; Borroni, S; Bortfeldt, J; Bortolotto, V; Bos, K; Boscherini, D; Bosman, M; Boudreau, J; Bouffard, J; Bouhova-Thacker, E V; Boumediene, D; Bourdarios, C; Bousson, N; Boutle, S K; Boveia, A; Boyd, J; Boyko, I R; Bozic, I; Bracinik, J; Brandt, A; Brandt, G; Brandt, O; Bratzler, U; Brau, B; Brau, J E; Braun, H M; Breaden Madden, W D; Brendlinger, K; Brennan, A J; Brenner, L; Brenner, R; Bressler, S; Bristow, T M; Britton, D; Britzger, D; Brochu, F M; Brock, I; Brock, R; Bronner, J; Brooijmans, G; Brooks, T; Brooks, W K; Brosamer, J; Brost, E; Bruckman de Renstrom, P A; Bruncko, D; Bruneliere, R; Bruni, A; Bruni, G; Bruschi, M; Bruscino, N; Bryngemark, L; Buanes, T; Buat, Q; Buchholz, P; Buckley, A G; Budagov, I A; Buehrer, F; Bugge, L; Bugge, M K; Bulekov, O; Bullock, D; Burckhart, H; Burdin, S; Burgard, C D; Burghgrave, B; Burke, S; Burmeister, I; Busato, E; Büscher, D; Büscher, V; Bussey, P; Butler, J M; Butt, A I; Buttar, C M; Butterworth, J M; Butti, P; Buttinger, W; Buzatu, A; Buzykaev, A R; Cabrera Urbán, S; Caforio, D; Cairo, V M; Cakir, O; Calace, N; Calafiura, P; Calandri, A; Calderini, G; Calfayan, P; Caloba, L P; Calvet, D; Calvet, S; Camacho Toro, R; Camarda, S; Camarri, P; Cameron, D; Caminal Armadans, R; Campana, S; Campanelli, M; Campoverde, A; Canale, V; Canepa, A; Cano Bret, M; Cantero, J; Cantrill, R; Cao, T; Capeans Garrido, M D M; Caprini, I; Caprini, M; Capua, M; Caputo, R; Carbone, R M; Cardarelli, R; Cardillo, F; Carli, T; Carlino, G; Carminati, L; Caron, S; Carquin, E; Carrillo-Montoya, G D; Carter, J R; Carvalho, J; Casadei, D; Casado, M P; Casolino, M; Casper, D W; Castaneda-Miranda, E; Castelli, A; Castillo Gimenez, V; Castro, N F; Catastini, P; Catinaccio, A; Catmore, J R; Cattai, A; Caudron, J; Cavaliere, V; Cavalli, D; Cavalli-Sforza, M; Cavasinni, V; Ceradini, F; Cerda Alberich, L; Cerio, B C; Cerny, K; Cerqueira, A S; Cerri, A; Cerrito, L; Cerutti, F; Cerv, M; Cervelli, A; Cetin, S A; Chafaq, A; Chakraborty, D; Chalupkova, I; Chan, Y L; Chang, P; Chapman, J D; Charlton, D G; Chau, C C; Chavez Barajas, C A; Che, S; Cheatham, S; Chegwidden, A; Chekanov, S; Chekulaev, S V; Chelkov, G A; Chelstowska, M A; Chen, C; Chen, H; Chen, K; Chen, L; Chen, S; Chen, S; Chen, X; Chen, Y; Cheng, H C; Cheng, Y; Cheplakov, A; Cheremushkina, E; Cherkaoui El Moursli, R; Chernyatin, V; Cheu, E; Chevalier, L; Chiarella, V; Chiarelli, G; Chiodini, G; Chisholm, A S; Chislett, R T; Chitan, A; Chizhov, M V; Choi, K; Chouridou, S; Chow, B K B; Christodoulou, V; Chromek-Burckhart, D; Chudoba, J; Chuinard, A J; Chwastowski, J J; Chytka, L; Ciapetti, G; Ciftci, A K; Cinca, D; Cindro, V; Cioara, I A; Ciocio, A; Cirotto, F; Citron, Z H; Ciubancan, M; Clark, A; Clark, B L; Clark, P J; Clarke, R N; Clement, C; Coadou, Y; Cobal, M; Coccaro, A; Cochran, J; Coffey, L; Colasurdo, L; Cole, B; Cole, S; Colijn, A P; Collot, J; Colombo, T; Compostella, G; Conde Muiño, P; Coniavitis, E; Connell, S H; Connelly, I A; Consorti, V; Constantinescu, S; Conta, C; Conti, G; Conventi, F; Cooke, M; Cooper, B D; Cooper-Sarkar, A M; Cornelissen, T; Corradi, M; Corriveau, F; Corso-Radu, A; Cortes-Gonzalez, A; Cortiana, G; Costa, G; Costa, M J; Costanzo, D; Côté, D; Cottin, G; Cowan, G; Cox, B E; Cranmer, K; Crawley, S J; Cree, G; Crépé-Renaudin, S; Crescioli, F; Cribbs, W A; Crispin Ortuzar, M; Cristinziani, M; Croft, V; Crosetti, G; Cuhadar Donszelmann, T; Cummings, J; Curatolo, M; Cúth, J; Cuthbert, C; Czirr, H; Czodrowski, P; D'Auria, S; D'Onofrio, M; Da Cunha Sargedas De Sousa, M J; Da Via, C; Dabrowski, W; Dafinca, A; Dai, T; Dale, O; Dallaire, F; Dallapiccola, C; Dam, M; Dandoy, J R; Dang, N P; Daniells, A C; Danninger, M; Dano Hoffmann, M; Dao, V; Darbo, G; Darmora, S; Dassoulas, J; Dattagupta, A; Davey, W; David, C; Davidek, T; Davies, E; Davies, M; Davison, P; Davygora, Y; Dawe, E; Dawson, I; Daya-Ishmukhametova, R K; De, K; de Asmundis, R; De Benedetti, A; De Castro, S; De Cecco, S; De Groot, N; de Jong, P; De la Torre, H; De Lorenzi, F; De Pedis, D; De Salvo, A; De Sanctis, U; De Santo, A; De Vivie De Regie, J B; Dearnaley, W J; Debbe, R; Debenedetti, C; Dedovich, D V; Deigaard, I; Del Peso, J; Del Prete, T; Delgove, D; Deliot, F; Delitzsch, C M; Deliyergiyev, M; Dell'Acqua, A; Dell'Asta, L; Dell'Orso, M; Della Pietra, M; Della Volpe, D; Delmastro, M; Delsart, P A; Deluca, C; DeMarco, D A; Demers, S; Demichev, M; Demilly, A; Denisov, S P; Derendarz, D; Derkaoui, J E; Derue, F; Dervan, P; Desch, K; Deterre, C; Dette, K; Deviveiros, P O; Dewhurst, A; Dhaliwal, S; Di Ciaccio, A; Di Ciaccio, L; Di Domenico, A; Di Donato, C; Di Girolamo, A; Di Girolamo, B; Di Mattia, A; Di Micco, B; Di Nardo, R; Di Simone, A; Di Sipio, R; Di Valentino, D; Diaconu, C; Diamond, M; Dias, F A; Diaz, M A; Diehl, E B; Dietrich, J; Diglio, S; Dimitrievska, A; Dingfelder, J; Dita, P; Dita, S; Dittus, F; Djama, F; Djobava, T; Djuvsland, J I; do Vale, M A B; Dobos, D; Dobre, M; Doglioni, C; Dohmae, T; Dolejsi, J; Dolezal, Z; Dolgoshein, B A; Donadelli, M; Donati, S; Dondero, P; Donini, J; Dopke, J; Doria, A; Dova, M T; Doyle, A T; Drechsler, E; Dris, M; Du, Y; Dubreuil, E; Duchovni, E; Duckeck, G; Ducu, O A; Duda, D; Dudarev, A; Duflot, L; Duguid, L; Dührssen, M; Dunford, M; Duran Yildiz, H; Düren, M; Durglishvili, A; Duschinger, D; Dutta, B; Dyndal, M; Eckardt, C; Ecker, K M; Edgar, R C; Edson, W; Edwards, N C; Ehrenfeld, W; Eifert, T; Eigen, G; Einsweiler, K; Ekelof, T; El Kacimi, M; Ellert, M; Elles, S; Ellinghaus, F; Elliot, A A; Ellis, N; Elmsheuser, J; Elsing, M; Emeliyanov, D; Enari, Y; Endner, O C; Endo, M; Erdmann, J; Ereditato, A; Ernis, G; Ernst, J; Ernst, M; Errede, S; Ertel, E; Escalier, M; Esch, H; Escobar, C; Esposito, B; Etienvre, A I; Etzion, E; Evans, H; Ezhilov, A; Fabbri, L; Facini, G; Fakhrutdinov, R M; Falciano, S; Falla, R J; Faltova, J; Fang, Y; Fanti, M; Farbin, A; Farilla, A; Farooque, T; Farrell, S; Farrington, S M; Farthouat, P; Fassi, F; Fassnacht, P; Fassouliotis, D; Faucci Giannelli, M; Favareto, A; Fayard, L; Fedin, O L; Fedorko, W; Feigl, S; Feligioni, L; Feng, C; Feng, E J; Feng, H; Fenyuk, A B; Feremenga, L; Fernandez Martinez, P; Fernandez Perez, S; Ferrando, J; Ferrari, A; Ferrari, P; Ferrari, R; Ferreira de Lima, D E; Ferrer, A; Ferrere, D; Ferretti, C; Ferretto Parodi, A; Fiascaris, M; Fiedler, F; Filipčič, A; Filipuzzi, M; Filthaut, F; Fincke-Keeler, M; Finelli, K D; Fiolhais, M C N; Fiorini, L; Firan, A; Fischer, A; Fischer, C; Fischer, J; Fisher, W C; Flaschel, N; Fleck, I; Fleischmann, P; Fletcher, G T; Fletcher, G; Fletcher, R R M; Flick, T; Floderus, A; Flores Castillo, L R; Flowerdew, M J; Forcolin, G T; Formica, A; Forti, A; Fournier, D; Fox, H; Fracchia, S; Francavilla, P; Franchini, M; Francis, D; Franconi, L; Franklin, M; Frate, M; Fraternali, M; Freeborn, D; French, S T; Fressard-Batraneanu, S M; Friedrich, F; Froidevaux, D; Frost, J A; Fukunaga, C; Fullana Torregrosa, E; Fulsom, B G; Fusayasu, T; Fuster, J; Gabaldon, C; Gabizon, O; Gabrielli, A; Gabrielli, A; Gach, G P; Gadatsch, S; Gadomski, S; Gagliardi, G; Gagnon, P; Galea, C; Galhardo, B; Gallas, E J; Gallop, B J; Gallus, P; Galster, G; Gan, K K; Gao, J; Gao, Y; Gao, Y S; Garay Walls, F M; García, C; García Navarro, J E; Garcia-Sciveres, M; Gardner, R W; Garelli, N; Garonne, V; Gatti, C; Gaudiello, A; Gaudio, G; Gaur, B; Gauthier, L; Gauzzi, P; Gavrilenko, I L; Gay, C; Gaycken, G; Gazis, E N; Ge, P; Gecse, Z; Gee, C N P; Geich-Gimbel, Ch; Geisler, M P; Gemme, C; Genest, M H; Geng, C; Gentile, S; George, S; Gerbaudo, D; Gershon, A; Ghasemi, S; Ghazlane, H; Giacobbe, B; Giagu, S; Giangiobbe, V; Giannetti, P; Gibbard, B; Gibson, S M; Gignac, M; Gilchriese, M; Gillam, T P S; Gillberg, D; Gilles, G; Gingrich, D M; Giokaris, N; Giordani, M P; Giorgi, F M; Giorgi, F M; Giraud, P F; Giromini, P; Giugni, D; Giuliani, C; Giulini, M; Gjelsten, B K; Gkaitatzis, S; Gkialas, I; Gkougkousis, E L; Gladilin, L K; Glasman, C; Glatzer, J; Glaysher, P C F; Glazov, A; Goblirsch-Kolb, M; Goddard, J R; Godlewski, J; Goldfarb, S; Golling, T; Golubkov, D; Gomes, A; Gonçalo, R; Goncalves Pinto Firmino Da Costa, J; Gonella, L; González de la Hoz, S; Gonzalez Parra, G; Gonzalez-Sevilla, S; Goossens, L; Gorbounov, P A; Gordon, H A; Gorelov, I; Gorini, B; Gorini, E; Gorišek, A; Gornicki, E; Goshaw, A T; Gössling, C; Gostkin, M I; Goujdami, D; Goussiou, A G; Govender, N; Gozani, E; Graber, L; Grabowska-Bold, I; Gradin, P O J; Grafström, P; Gramling, J; Gramstad, E; Grancagnolo, S; Gratchev, V; Gray, H M; Graziani, E; Greenwood, Z D; Grefe, C; Gregersen, K; Gregor, I M; Grenier, P; Griffiths, J; Grillo, A A; Grimm, K; Grinstein, S; Gris, Ph; Grivaz, J-F; Groh, S; Grohs, J P; Grohsjean, A; Gross, E; Grosse-Knetter, J; Grossi, G C; Grout, Z J; Guan, L; Guenther, J; Guescini, F; Guest, D; Gueta, O; Guido, E; Guillemin, T; Guindon, S; Gul, U; Gumpert, C; Guo, J; Guo, Y; Gupta, S; Gustavino, G; Gutierrez, P; Gutierrez Ortiz, N G; Gutschow, C; Guyot, C; Gwenlan, C; Gwilliam, C B; Haas, A; Haber, C; Hadavand, H K; Haddad, N; Haefner, P; Hageböck, S; Hajduk, Z; Hakobyan, H; Haleem, M; Haley, J; Hall, D; Halladjian, G; Hallewell, G D; Hamacher, K; Hamal, P; Hamano, K; Hamilton, A; Hamity, G N; Hamnett, P G; Han, L; Hanagaki, K; Hanawa, K; Hance, M; Haney, B; Hanke, P; Hanna, R; Hansen, J B; Hansen, J D; Hansen, M C; Hansen, P H; Hara, K; Hard, A S; Harenberg, T; Hariri, F; Harkusha, S; Harrington, R D; Harrison, P F; Hartjes, F; Hasegawa, M; Hasegawa, Y; Hasib, A; Hassani, S; Haug, S; Hauser, R; Hauswald, L; Havranek, M; Hawkes, C M; Hawkings, R J; Hawkins, A D; Hayashi, T; Hayden, D; Hays, C P; Hays, J M; Hayward, H S; Haywood, S J; Head, S J; Heck, T; Hedberg, V; Heelan, L; Heim, S; Heim, T; Heinemann, B; Heinrich, L; Hejbal, J; Helary, L; Hellman, S; Helsens, C; Henderson, J; Henderson, R C W; Heng, Y; Hengler, C; Henkelmann, S; Henriques Correia, A M; Henrot-Versille, S; Herbert, G H; Hernández Jiménez, Y; Herten, G; Hertenberger, R; Hervas, L; Hesketh, G G; Hessey, N P; Hetherly, J W; Hickling, R; Higón-Rodriguez, E; Hill, E; Hill, J C; Hiller, K H; Hillier, S J; Hinchliffe, I; Hines, E; Hinman, R R; Hirose, M; Hirschbuehl, D; Hobbs, J; Hod, N; Hodgkinson, M C; Hodgson, P; Hoecker, A; Hoeferkamp, M R; Hoenig, F; Hohlfeld, M; Hohn, D; Holmes, T R; Homann, M; Hong, T M; Hooberman, B H; Hopkins, W H; Horii, Y; Horton, A J; Hostachy, J-Y; Hou, S; Hoummada, A; Howard, J; Howarth, J; Hrabovsky, M; Hristova, I; Hrivnac, J; Hryn'ova, T; Hrynevich, A; Hsu, C; Hsu, P J; Hsu, S-C; Hu, D; Hu, Q; Hu, X; Huang, Y; Hubacek, Z; Hubaut, F; Huegging, F; Huffman, T B; Hughes, E W; Hughes, G; Huhtinen, M; Hülsing, T A; Huseynov, N; Huston, J; Huth, J; Iacobucci, G; Iakovidis, G; Ibragimov, I; Iconomidou-Fayard, L; Ideal, E; Idrissi, Z; Iengo, P; Igonkina, O; Iizawa, T; Ikegami, Y; Ikeno, M; Ilchenko, Y; Iliadis, D; Ilic, N; Ince, T; Introzzi, G; Ioannou, P; Iodice, M; Iordanidou, K; Ippolito, V; Irles Quiles, A; Isaksson, C; Ishino, M; Ishitsuka, M; Ishmukhametov, R; Issever, C; Istin, S; Iturbe Ponce, J M; Iuppa, R; Ivarsson, J; Iwanski, W; Iwasaki, H; Izen, J M; Izzo, V; Jabbar, S; Jackson, B; Jackson, M; Jackson, P; Jaekel, M R; Jain, V; Jakobi, K B; Jakobs, K; Jakobsen, S; Jakoubek, T; Jakubek, J; Jamin, D O; Jana, D K; Jansen, E; Jansky, R; Janssen, J; Janus, M; Jarlskog, G; Javadov, N; Javůrek, T; Jeanty, L; Jejelava, J; Jeng, G-Y; Jennens, D; Jenni, P; Jentzsch, J; Jeske, C; Jézéquel, S; Ji, H; Jia, J; Jiang, H; Jiang, Y; Jiggins, S; Jimenez Pena, J; Jin, S; Jinaru, A; Jinnouchi, O; Joergensen, M D; Johansson, P; Johns, K A; Johnson, W J; Jon-And, K; Jones, G; Jones, R W L; Jones, T J; Jongmanns, J; Jorge, P M; Joshi, K D; Jovicevic, J; Ju, X; Juste Rozas, A; Kaci, M; Kaczmarska, A; Kado, M; Kagan, H; Kagan, M; Kahn, S J; Kajomovitz, E; Kalderon, C W; Kaluza, A; Kama, S; Kamenshchikov, A; Kanaya, N; Kaneti, S; Kantserov, V A; Kanzaki, J; Kaplan, B; Kaplan, L S; Kapliy, A; Kar, D; Karakostas, K; Karamaoun, A; Karastathis, N; Kareem, M J; Karentzos, E; Karnevskiy, M; Karpov, S N; Karpova, Z M; Karthik, K; Kartvelishvili, V; Karyukhin, A N; Kasahara, K; Kashif, L; Kass, R D; Kastanas, A; Kataoka, Y; Kato, C; Katre, A; Katzy, J; Kawade, K; Kawagoe, K; Kawamoto, T; Kawamura, G; Kazama, S; Kazanin, V F; Keeler, R; Kehoe, R; Keller, J S; Kempster, J J; Keoshkerian, H; Kepka, O; Kerševan, B P; Kersten, S; Keyes, R A; Khalil-Zada, F; Khandanyan, H; Khanov, A; Kharlamov, A G; Khoo, T J; Khovanskiy, V; Khramov, E; Khubua, J; Kido, S; Kim, H Y; Kim, S H; Kim, Y K; Kimura, N; Kind, O M; King, B T; King, M; King, S B; Kirk, J; Kiryunin, A E; Kishimoto, T; Kisielewska, D; Kiss, F; Kiuchi, K; Kivernyk, O; Kladiva, E; Klein, M H; Klein, M; Klein, U; Kleinknecht, K; Klimek, P; Klimentov, A; Klingenberg, R; Klinger, J A; Klioutchnikova, T; Kluge, E-E; Kluit, P; Kluth, S; Knapik, J; Kneringer, E; Knoops, E B F G; Knue, A; Kobayashi, A; Kobayashi, D; Kobayashi, T; Kobel, M; Kocian, M; Kodys, P; Koffas, T; Koffeman, E; Kogan, L A; Kohlmann, S; Kohout, Z; Kohriki, T; Koi, T; Kolanoski, H; Kolb, M; Koletsou, I; Komar, A A; Komori, Y; Kondo, T; Kondrashova, N; Köneke, K; König, A C; Kono, T; Konoplich, R; Konstantinidis, N; Kopeliansky, R; Koperny, S; Köpke, L; Kopp, A K; Korcyl, K; Kordas, K; Korn, A; Korol, A A; Korolkov, I; Korolkova, E V; Kortner, O; Kortner, S; Kosek, T; Kostyukhin, V V; Kotov, V M; Kotwal, A; Kourkoumeli-Charalampidi, A; Kourkoumelis, C; Kouskoura, V; Koutsman, A; Kowalewski, R; Kowalski, T Z; Kozanecki, W; Kozhin, A S; Kramarenko, V A; Kramberger, G; Krasnopevtsev, D; Krasny, M W; Krasznahorkay, A; Kraus, J K; Kravchenko, A; Kreiss, S; Kretz, M; Kretzschmar, J; Kreutzfeldt, K; Krieger, P; Krizka, K; Kroeninger, K; Kroha, H; Kroll, J; Kroseberg, J; Krstic, J; Kruchonak, U; Krüger, H; Krumnack, N; Kruse, A; Kruse, M C; Kruskal, M; Kubota, T; Kucuk, H; Kuday, S; Kuehn, S; Kugel, A; Kuger, F; Kuhl, A; Kuhl, T; Kukhtin, V; Kukla, R; Kulchitsky, Y; Kuleshov, S; Kuna, M; Kunigo, T; Kupco, A; Kurashige, H; Kurochkin, Y A; Kus, V; Kuwertz, E S; Kuze, M; Kvita, J; Kwan, T; Kyriazopoulos, D; La Rosa, A; La Rosa Navarro, J L; La Rotonda, L; Lacasta, C; Lacava, F; Lacey, J; Lacker, H; Lacour, D; Lacuesta, V R; Ladygin, E; Lafaye, R; Laforge, B; Lagouri, T; Lai, S; Lambourne, L; Lammers, S; Lampen, C L; Lampl, W; Lançon, E; Landgraf, U; Landon, M P J; Lang, V S; Lange, J C; Lankford, A J; Lanni, F; Lantzsch, K; Lanza, A; Laplace, S; Lapoire, C; Laporte, J F; Lari, T; Lasagni Manghi, F; Lassnig, M; Laurelli, P; Lavrijsen, W; Law, A T; Laycock, P; Lazovich, T; Le Dortz, O; Le Guirriec, E; Le Menedeu, E; LeBlanc, M; LeCompte, T; Ledroit-Guillon, F; Lee, C A; Lee, S C; Lee, L; Lefebvre, G; Lefebvre, M; Legger, F; Leggett, C; Lehan, A; Lehmann Miotto, G; Lei, X; Leight, W A; Leisos, A; Leister, A G; Leite, M A L; Leitner, R; Lellouch, D; Lemmer, B; Leney, K J C; Lenz, T; Lenzi, B; Leone, R; Leone, S; Leonidopoulos, C; Leontsinis, S; Leroy, C; Lester, C G; Levchenko, M; Levêque, J; Levin, D; Levinson, L J; Levy, M; Lewis, A; Leyko, A M; Leyton, M; Li, B; Li, H; Li, H L; Li, L; Li, L; Li, S; Li, X; Li, Y; Liang, Z; Liao, H; Liberti, B; Liblong, A; Lichard, P; Lie, K; Liebal, J; Liebig, W; Limbach, C; Limosani, A; Lin, S C; Lin, T H; Linde, F; Lindquist, B E; Linnemann, J T; Lipeles, E; Lipniacka, A; Lisovyi, M; Liss, T M; Lissauer, D; Lister, A; Litke, A M; Liu, B; Liu, D; Liu, H; Liu, J; Liu, J B; Liu, K; Liu, L; Liu, M; Liu, M; Liu, Y; Livan, M; Lleres, A; Llorente Merino, J; Lloyd, S L; Lo Sterzo, F; Lobodzinska, E; Loch, P; Lockman, W S; Loebinger, F K; Loevschall-Jensen, A E; Loew, K M; Loginov, A; Lohse, T; Lohwasser, K; Lokajicek, M; Long, B A; Long, J D; Long, R E; Looper, K A; Lopes, L; Lopez Mateos, D; Lopez Paredes, B; Lopez Paz, I; Lorenz, J; Lorenzo Martinez, N; Losada, M; Lösel, P J; Lou, X; Lounis, A; Love, J; Love, P A; Lu, H; Lu, N; Lubatti, H J; Luci, C; Lucotte, A; Luedtke, C; Luehring, F; Lukas, W; Luminari, L; Lundberg, O; Lund-Jensen, B; Lynn, D; Lysak, R; Lytken, E; Ma, H; Ma, L L; Maccarrone, G; Macchiolo, A; Macdonald, C M; Maček, B; Machado Miguens, J; Macina, D; Madaffari, D; Madar, R; Maddocks, H J; Mader, W F; Madsen, A; Maeda, J; Maeland, S; Maeno, T; Maevskiy, A; Magradze, E; Mahboubi, K; Mahlstedt, J; Maiani, C; Maidantchik, C; Maier, A A; Maier, T; Maio, A; Majewski, S; Makida, Y; Makovec, N; Malaescu, B; Malecki, Pa; Maleev, V P; Malek, F; Mallik, U; Malon, D; Malone, C; Maltezos, S; Malyshev, V M; Malyukov, S; Mamuzic, J; Mancini, G; Mandelli, B; Mandelli, L; Mandić, I; Mandrysch, R; Maneira, J; Manhaes de Andrade Filho, L; Manjarres Ramos, J; Mann, A; Manousakis-Katsikakis, A; Mansoulie, B; Mantifel, R; Mantoani, M; Mapelli, L; March, L; Marchiori, G; Marcisovsky, M; Marino, C P; Marjanovic, M; Marley, D E; Marroquim, F; Marsden, S P; Marshall, Z; Marti, L F; Marti-Garcia, S; Martin, B; Martin, T A; Martin, V J; Martin Dit Latour, B; Martinez, M; Martin-Haugh, S; Martoiu, V S; Martyniuk, A C; Marx, M; Marzano, F; Marzin, A; Masetti, L; Mashimo, T; Mashinistov, R; Masik, J; Maslennikov, A L; Massa, I; Massa, L; Mastrandrea, P; Mastroberardino, A; Masubuchi, T; Mättig, P; Mattmann, J; Maurer, J; Maxfield, S J; Maximov, D A; Mazini, R; Mazza, S M; Mc Goldrick, G; Mc Kee, S P; McCarn, A; McCarthy, R L; McCarthy, T G; McCubbin, N A; McFarlane, K W; Mcfayden, J A; Mchedlidze, G; McMahon, S J; McPherson, R A; Medinnis, M; Meehan, S; Mehlhase, S; Mehta, A; Meier, K; Meineck, C; Meirose, B; Mellado Garcia, B R; Meloni, F; Mengarelli, A; Menke, S; Meoni, E; Mercurio, K M; Mergelmeyer, S; Mermod, P; Merola, L; Meroni, C; Merritt, F S; Messina, A; Metcalfe, J; Mete, A S; Meyer, C; Meyer, C; Meyer, J-P; Meyer, J; Meyer Zu Theenhausen, H; Middleton, R P; Miglioranzi, S; Mijović, L; Mikenberg, G; Mikestikova, M; Mikuž, M; Milesi, M; Milic, A; Miller, D W; Mills, C; Milov, A; Milstead, D A; Minaenko, A A; Minami, Y; Minashvili, I A; Mincer, A I; Mindur, B; Mineev, M; Ming, Y; Mir, L M; Mistry, K P; Mitani, T; Mitrevski, J; Mitsou, V A; Miucci, A; Miyagawa, P S; Mjörnmark, J U; Moa, T; Mochizuki, K; Mohapatra, S; Mohr, W; Molander, S; Moles-Valls, R; Monden, R; Mondragon, M C; Mönig, K; Monini, C; Monk, J; Monnier, E; Montalbano, A; Montejo Berlingen, J; Monticelli, F; Monzani, S; Moore, R W; Morange, N; Moreno, D; Moreno Llácer, M; Morettini, P; Mori, D; Mori, T; Morii, M; Morinaga, M; Morisbak, V; Moritz, S; Morley, A K; Mornacchi, G; Morris, J D; Mortensen, S S; Morton, A; Morvaj, L; Mosidze, M; Moss, J; Motohashi, K; Mount, R; Mountricha, E; Mouraviev, S V; Moyse, E J W; Muanza, S; Mudd, R D; Mueller, F; Mueller, J; Mueller, R S P; Mueller, T; Muenstermann, D; Mullen, P; Mullier, G A; Munoz Sanchez, F J; Murillo Quijada, J A; Murray, W J; Musheghyan, H; Musto, E; Myagkov, A G; Myska, M; Nachman, B P; Nackenhorst, O; Nadal, J; Nagai, K; Nagai, R; Nagai, Y; Nagano, K; Nagarkar, A; Nagasaka, Y; Nagata, K; Nagel, M; Nagy, E; Nairz, A M; Nakahama, Y; Nakamura, K; Nakamura, T; Nakano, I; Namasivayam, H; Naranjo Garcia, R F; Narayan, R; Narrias Villar, D I; Naumann, T; Navarro, G; Nayyar, R; Neal, H A; Nechaeva, P Yu; Neep, T J; Nef, P D; Negri, A; Negrini, M; Nektarijevic, S; Nellist, C; Nelson, A; Nemecek, S; Nemethy, P; Nepomuceno, A A; Nessi, M; Neubauer, M S; Neumann, M; Neves, R M; Nevski, P; Newman, P R; Nguyen, D H; Nickerson, R B; Nicolaidou, R; Nicquevert, B; Nielsen, J; Nikiforou, N; Nikiforov, A; Nikolaenko, V; Nikolic-Audit, I; Nikolopoulos, K; Nilsen, J K; Nilsson, P; Ninomiya, Y; Nisati, A; Nisius, R; Nobe, T; Nodulman, L; Nomachi, M; Nomidis, I; Nooney, T; Norberg, S; Nordberg, M; Novgorodova, O; Nowak, S; Nozaki, M; Nozka, L; Ntekas, K; Nunnemann, T; Nurse, E; Nuti, F; O'grady, F; O'Neil, D C; O'Shea, V; Oakham, F G; Oberlack, H; Obermann, T; Ocariz, J; Ochi, A; Ochoa, I; Ochoa-Ricoux, J P; Oda, S; Odaka, S; Ogren, H; Oh, A; Oh, S H; Ohm, C C; Ohman, H; Oide, H; Okamura, W; Okawa, H; Okumura, Y; Okuyama, T; Olariu, A; Olivares Pino, S A; Oliveira Damazio, D; Olszewski, A; Olszowska, J; Onofre, A; Onogi, K; Onyisi, P U E; Oram, C J; Oreglia, M J; Oren, Y; Orestano, D; Orlando, N; Oropeza Barrera, C; Orr, R S; Osculati, B; Ospanov, R; Otero Y Garzon, G; Otono, H; Ouchrif, M; Ould-Saada, F; Ouraou, A; Oussoren, K P; Ouyang, Q; Ovcharova, A; Owen, M; Owen, R E; Ozcan, V E; Ozturk, N; Pachal, K; Pacheco Pages, A; Padilla Aranda, C; Pagáčová, M; Pagan Griso, S; Paganis, E; Paige, F; Pais, P; Pajchel, K; Palacino, G; Palestini, S; Palka, M; Pallin, D; Palma, A; Pan, Y B; Panagiotopoulou, E St; Pandini, C E; Panduro Vazquez, J G; Pani, P; Panitkin, S; Pantea, D; Paolozzi, L; Papadopoulou, Th D; Papageorgiou, K; Paramonov, A; Paredes Hernandez, D; Parker, M A; Parker, K A; Parodi, F; Parsons, J A; Parzefall, U; Pasqualucci, E; Passaggio, S; Pastore, F; Pastore, Fr; Pásztor, G; Pataraia, S; Patel, N D; Pater, J R; Pauly, T; Pearce, J; Pearson, B; Pedersen, L E; Pedersen, M; Pedraza Lopez, S; Pedro, R; Peleganchuk, S V; Pelikan, D; Penc, O; Peng, C; Peng, H; Penning, B; Penwell, J; Perepelitsa, D V; Perez Codina, E; Pérez García-Estañ, M T; Perini, L; Pernegger, H; Perrella, S; Peschke, R; Peshekhonov, V D; Peters, K; Peters, R F Y; Petersen, B A; Petersen, T C; Petit, E; Petridis, A; Petridou, C; Petroff, P; Petrolo, E; Petrucci, F; Pettersson, N E; Pezoa, R; Phillips, P W; Piacquadio, G; Pianori, E; Picazio, A; Piccaro, E; Piccinini, M; Pickering, M A; Piegaia, R; Pignotti, D T; Pilcher, J E; Pilkington, A D; Pin, A W J; Pina, J; Pinamonti, M; Pinfold, J L; Pingel, A; Pires, S; Pirumov, H; Pitt, M; Pizio, C; Plazak, L; Pleier, M-A; Pleskot, V; Plotnikova, E; Plucinski, P; Pluth, D; Poettgen, R; Poggioli, L; Pohl, D; Polesello, G; Poley, A; Policicchio, A; Polifka, R; Polini, A; Pollard, C S; Polychronakos, V; Pommès, K; Pontecorvo, L; Pope, B G; Popeneciu, G A; Popovic, D S; Poppleton, A; Pospisil, S; Potamianos, K; Potrap, I N; Potter, C J; Potter, C T; Poulard, G; Poveda, J; Pozdnyakov, V; Pozo Astigarraga, M E; Pralavorio, P; Pranko, A; Prasad, S; Prell, S; Price, D; Price, L E; Primavera, M; Prince, S; Proissl, M; Prokofiev, K; Prokoshin, F; Protopapadaki, E; Protopopescu, S; Proudfoot, J; Przybycien, M; Ptacek, E; Puddu, D; Pueschel, E; Puldon, D; Purohit, M; Puzo, P; Qian, J; Qin, G; Qin, Y; Quadt, A; Quarrie, D R; Quayle, W B; Queitsch-Maitland, M; Quilty, D; Raddum, S; Radeka, V; Radescu, V; Radhakrishnan, S K; Radloff, P; Rados, P; Ragusa, F; Rahal, G; Rajagopalan, S; Rammensee, M; Rangel-Smith, C; Rauscher, F; Rave, S; Ravenscroft, T; Raymond, M; Read, A L; Readioff, N P; Rebuzzi, D M; Redelbach, A; Redlinger, G; Reece, R; Reeves, K; Rehnisch, L; Reichert, J; Reisin, H; Rembser, C; Ren, H; Renaud, A; Rescigno, M; Resconi, S; Rezanova, O L; Reznicek, P; Rezvani, R; Richter, R; Richter, S; Richter-Was, E; Ricken, O; Ridel, M; Rieck, P; Riegel, C J; Rieger, J; Rifki, O; Rijssenbeek, M; Rimoldi, A; Rinaldi, L; Ristić, B; Ritsch, E; Riu, I; Rizatdinova, F; Rizvi, E; Robertson, S H; Robichaud-Veronneau, A; Robinson, D; Robinson, J E M; Robson, A; Roda, C; Roe, S; Røhne, O; Romaniouk, A; Romano, M; Romano Saez, S M; Romero Adam, E; Rompotis, N; Ronzani, M; Roos, L; Ros, E; Rosati, S; Rosbach, K; Rose, P; Rosenthal, O; Rossetti, V; Rossi, E; Rossi, L P; Rosten, J H N; Rosten, R; Rotaru, M; Roth, I; Rothberg, J; Rousseau, D; Royon, C R; Rozanov, A; Rozen, Y; Ruan, X; Rubbo, F; Rubinskiy, I; Rud, V I; Rudolph, C; Rudolph, M S; Rühr, F; Ruiz-Martinez, A; Rurikova, Z; Rusakovich, N A; Ruschke, A; Russell, H L; Rutherfoord, J P; Ruthmann, N; Ryabov, Y F; Rybar, M; Rybkin, G; Ryder, N C; Ryzhov, A; Saavedra, A F; Sabato, G; Sacerdoti, S; Saddique, A; Sadrozinski, H F-W; Sadykov, R; Safai Tehrani, F; Saha, P; Sahinsoy, M; Saimpert, M; Saito, T; Sakamoto, H; Sakurai, Y; Salamanna, G; Salamon, A; Salazar Loyola, J E; Saleem, M; Salek, D; Sales De Bruin, P H; Salihagic, D; Salnikov, A; Salt, J; Salvatore, D; Salvatore, F; Salvucci, A; Salzburger, A; Sammel, D; Sampsonidis, D; Sanchez, A; Sánchez, J; Sanchez Martinez, V; Sandaker, H; Sandbach, R L; Sander, H G; Sanders, M P; Sandhoff, M; Sandoval, C; Sandstroem, R; Sankey, D P C; Sannino, M; Sansoni, A; Santoni, C; Santonico, R; Santos, H; Santoyo Castillo, I; Sapp, K; Sapronov, A; Saraiva, J G; Sarrazin, B; Sasaki, O; Sasaki, Y; Sato, K; Sauvage, G; Sauvan, E; Savage, G; Savard, P; Sawyer, C; Sawyer, L; Saxon, J; Sbarra, C; Sbrizzi, A; Scanlon, T; Scannicchio, D A; Scarcella, M; Scarfone, V; Schaarschmidt, J; Schacht, P; Schaefer, D; Schaefer, R; Schaeffer, J; Schaepe, S; Schaetzel, S; Schäfer, U; Schaffer, A C; Schaile, D; Schamberger, R D; Scharf, V; Schegelsky, V A; Scheirich, D; Schernau, M; Schiavi, C; Schillo, C; Schioppa, M; Schlenker, S; Schmieden, K; Schmitt, C; Schmitt, S; Schmitt, S; Schmitz, S; Schneider, B; Schnellbach, Y J; Schnoor, U; Schoeffel, L; Schoening, A; Schoenrock, B D; Schopf, E; Schorlemmer, A L S; Schott, M; Schouten, D; Schovancova, J; Schramm, S; Schreyer, M; Schuh, N; Schultens, M J; Schultz-Coulon, H-C; Schulz, H; Schumacher, M; Schumm, B A; Schune, Ph; Schwanenberger, C; Schwartzman, A; Schwarz, T A; Schwegler, Ph; Schweiger, H; Schwemling, Ph; Schwienhorst, R; Schwindling, J; Schwindt, T; Scifo, E; Sciolla, G; Scuri, F; Scutti, F; Searcy, J; Sedov, G; Sedykh, E; Seema, P; Seidel, S C; Seiden, A; Seifert, F; Seixas, J M; Sekhniaidze, G; Sekhon, K; Sekula, S J; Seliverstov, D M; Semprini-Cesari, N; Serfon, C; Serin, L; Serkin, L; Serre, T; Sessa, M; Seuster, R; Severini, H; Sfiligoj, T; Sforza, F; Sfyrla, A; Shabalina, E; Shamim, M; Shan, L Y; Shang, R; Shank, J T; Shapiro, M; Shatalov, P B; Shaw, K; Shaw, S M; Shcherbakova, A; Shehu, C Y; Sherwood, P; Shi, L; Shimizu, S; Shimmin, C O; Shimojima, M; Shiyakova, M; Shmeleva, A; Shoaleh Saadi, D; Shochet, M J; Shojaii, S; Shrestha, S; Shulga, E; Shupe, M A; Sicho, P; Sidebo, P E; Sidiropoulou, O; Sidorov, D; Sidoti, A; Siegert, F; Sijacki, Dj; Silva, J; Silver, Y; Silverstein, S B; Simak, V; Simard, O; Simic, Lj; Simion, S; Simioni, E; Simmons, B; Simon, D; Simon, M; Sinervo, P; Sinev, N B; Sioli, M; Siragusa, G; Sivoklokov, S Yu; Sjölin, J; Sjursen, T B; Skinner, M B; Skottowe, H P; Skubic, P; Slater, M; Slavicek, T; Slawinska, M; Sliwa, K; Smakhtin, V; Smart, B H; Smestad, L; Smirnov, S Yu; Smirnov, Y; Smirnova, L N; Smirnova, O; Smith, M N K; Smith, R W; Smizanska, M; Smolek, K; Snesarev, A A; Snidero, G; Snyder, S; Sobie, R; Socher, F; Soffer, A; Soh, D A; Sokhrannyi, G; Solans, C A; Solar, M; Solc, J; Soldatov, E Yu; Soldevila, U; Solodkov, A A; Soloshenko, A; Solovyanov, O V; Solovyev, V; Sommer, P; Song, H Y; Soni, N; Sood, A; Sopczak, A; Sopko, B; Sopko, V; Sorin, V; Sosa, D; Sosebee, M; Sotiropoulou, C L; Soualah, R; Soukharev, A M; South, D; Sowden, B C; Spagnolo, S; Spalla, M; Spangenberg, M; Spanò, F; Spearman, W R; Sperlich, D; Spettel, F; Spighi, R; Spigo, G; Spiller, L A; Spousta, M; St Denis, R D; Stabile, A; Staerz, S; Stahlman, J; Stamen, R; Stamm, S; Stanecka, E; Stanek, R W; Stanescu, C; Stanescu-Bellu, M; Stanitzki, M M; Stapnes, S; Starchenko, E A; Stark, J; Staroba, P; Starovoitov, P; Staszewski, R; Steinberg, P; Stelzer, B; Stelzer, H J; Stelzer-Chilton, O; Stenzel, H; Stewart, G A; Stillings, J A; Stockton, M C; Stoebe, M; Stoicea, G; Stolte, P; Stonjek, S; Stradling, A R; Straessner, A; Stramaglia, M E; Strandberg, J; Strandberg, S; Strandlie, A; Strauss, E; Strauss, M; Strizenec, P; Ströhmer, R; Strom, D M; Stroynowski, R; Strubig, A; Stucci, S A; Stugu, B; Styles, N A; Su, D; Su, J; Subramaniam, R; Succurro, A; Suchek, S; Sugaya, Y; Suk, M; Sulin, V V; Sultansoy, S; Sumida, T; Sun, S; Sun, X; Sundermann, J E; Suruliz, K; Susinno, G; Sutton, M R; Suzuki, S; Svatos, M; Swiatlowski, M; Sykora, I; Sykora, T; Ta, D; Taccini, C; Tackmann, K; Taenzer, J; Taffard, A; Tafirout, R; Taiblum, N; Takai, H; Takashima, R; Takeda, H; Takeshita, T; Takubo, Y; Talby, M; Talyshev, A A; Tam, J Y C; Tan, K G; Tanaka, J; Tanaka, R; Tanaka, S; Tannenwald, B B; Tapia Araya, S; Tapprogge, S; Tarem, S; Tarrade, F; Tartarelli, G F; Tas, P; Tasevsky, M; Tashiro, T; Tassi, E; Tavares Delgado, A; Tayalati, Y; Taylor, A C; Taylor, F E; Taylor, G N; Taylor, P T E; Taylor, W; Teischinger, F A; Teixeira-Dias, P; Temming, K K; Temple, D; Ten Kate, H; Teng, P K; Teoh, J J; Tepel, F; Terada, S; Terashi, K; Terron, J; Terzo, S; Testa, M; Teuscher, R J; Theveneaux-Pelzer, T; Thomas, J P; Thomas-Wilsker, J; Thompson, E N; Thompson, P D; Thompson, R J; Thompson, A S; Thomsen, L A; Thomson, E; Thomson, M; Thun, R P; Tibbetts, M J; Ticse Torres, R E; Tikhomirov, V O; Tikhonov, Yu A; Timoshenko, S; Tiouchichine, E; Tipton, P; Tisserant, S; Todome, K; Todorov, T; Todorova-Nova, S; Tojo, J; Tokár, S; Tokushuku, K; Tollefson, K; Tolley, E; Tomlinson, L; Tomoto, M; Tompkins, L; Toms, K; Torrence, E; Torres, H; Torró Pastor, E; Toth, J; Touchard, F; Tovey, D R; Trefzger, T; Tremblet, L; Tricoli, A; Trigger, I M; Trincaz-Duvoid, S; Tripiana, M F; Trischuk, W; Trocmé, B; Troncon, C; Trottier-McDonald, M; Trovatelli, M; Truong, L; Trzebinski, M; Trzupek, A; Tsarouchas, C; Tseng, J C-L; Tsiareshka, P V; Tsionou, D; Tsipolitis, G; Tsirintanis, N; Tsiskaridze, S; Tsiskaridze, V; Tskhadadze, E G; Tsui, K M; Tsukerman, I I; Tsulaia, V; Tsuno, S; Tsybychev, D; Tudorache, A; Tudorache, V; Tuna, A N; Tupputi, S A; Turchikhin, S; Turecek, D; Turra, R; Turvey, A J; Tuts, P M; Tykhonov, A; Tylmad, M; Tyndel, M; Ueda, I; Ueno, R; Ughetto, M; Ukegawa, F; Unal, G; Undrus, A; Unel, G; Ungaro, F C; Unno, Y; Unverdorben, C; Urban, J; Urquijo, P; Urrejola, P; Usai, G; Usanova, A; Vacavant, L; Vacek, V; Vachon, B; Valderanis, C; Valencic, N; Valentinetti, S; Valero, A; Valery, L; Valkar, S; Vallecorsa, S; Valls Ferrer, J A; Van Den Wollenberg, W; Van Der Deijl, P C; van der Geer, R; van der Graaf, H; van Eldik, N; van Gemmeren, P; Van Nieuwkoop, J; van Vulpen, I; van Woerden, M C; Vanadia, M; Vandelli, W; Vanguri, R; Vaniachine, A; Vannucci, F; Vardanyan, G; Vari, R; Varnes, E W; Varol, T; Varouchas, D; Vartapetian, A; Varvell, K E; Vazeille, F; Vazquez Schroeder, T; Veatch, J; Veloce, L M; Veloso, F; Velz, T; Veneziano, S; Ventura, A; Ventura, D; Venturi, M; Venturi, N; Venturini, A; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, J C; Vest, A; Vetterli, M C; Viazlo, O; Vichou, I; Vickey, T; Vickey Boeriu, O E; Viehhauser, G H A; Viel, S; Vigne, R; Villa, M; Villaplana Perez, M; Vilucchi, E; Vincter, M G; Vinogradov, V B; Vivarelli, I; Vlachos, S; Vladoiu, D; Vlasak, M; Vogel, M; Vokac, P; Volpi, G; Volpi, M; von der Schmitt, H; von Radziewski, H; von Toerne, E; Vorobel, V; Vorobev, K; Vos, M; Voss, R; Vossebeld, J H; Vranjes, N; Vranjes Milosavljevic, M; Vrba, V; Vreeswijk, M; Vuillermet, R; Vukotic, I; Vykydal, Z; Wagner, P; Wagner, W; Wahlberg, H; Wahrmund, S; Wakabayashi, J; Walder, J; Walker, R; Walkowiak, W; Wang, C; Wang, F; Wang, H; Wang, H; Wang, J; Wang, J; Wang, K; Wang, R; Wang, S M; Wang, T; Wang, T; Wang, X; Wanotayaroj, C; Warburton, A; Ward, C P; Wardrope, D R; Washbrook, A; Wasicki, C; Watkins, P M; Watson, A T; Watson, I J; Watson, M F; Watts, G; Watts, S; Waugh, B M; Webb, S; Weber, M S; Weber, S W; Webster, J S; Weidberg, A R; Weinert, B; Weingarten, J; Weiser, C; Weits, H; Wells, P S; Wenaus, T; Wengler, T; Wenig, S; Wermes, N; Werner, M; Werner, P; Wessels, M; Wetter, J; Whalen, K; Wharton, A M; White, A; White, M J; White, R; White, S; Whiteson, D; Wickens, F J; Wiedenmann, W; Wielers, M; Wienemann, P; Wiglesworth, C; Wiik-Fuchs, L A M; Wildauer, A; Wilkens, H G; Williams, H H; Williams, S; Willis, C; Willocq, S; Wilson, A; Wilson, J A; Wingerter-Seez, I; Winklmeier, F; Winter, B T; Wittgen, M; Wittkowski, J; Wollstadt, S J; Wolter, M W; Wolters, H; Wosiek, B K; Wotschack, J; Woudstra, M J; Wozniak, K W; Wu, M; Wu, M; Wu, S L; Wu, X; Wu, Y; Wyatt, T R; Wynne, B M; Xella, S; Xu, D; Xu, L; Yabsley, B; Yacoob, S; Yakabe, R; Yamada, M; Yamaguchi, D; Yamaguchi, Y; Yamamoto, A; Yamamoto, S; Yamanaka, T; Yamauchi, K; Yamazaki, Y; Yan, Z; Yang, H; Yang, H; Yang, Y; Yao, W-M; Yap, Y C; Yasu, Y; Yatsenko, E; Yau Wong, K H; Ye, J; Ye, S; Yeletskikh, I; Yen, A L; Yildirim, E; Yorita, K; Yoshida, R; Yoshihara, K; Young, C; Young, C J S; Youssef, S; Yu, D R; Yu, J; Yu, J M; Yu, J; Yuan, L; Yuen, S P Y; Yurkewicz, A; Yusuff, I; Zabinski, B; Zaidan, R; Zaitsev, A M; Zalieckas, J; Zaman, A; Zambito, S; Zanello, L; Zanzi, D; Zeitnitz, C; Zeman, M; Zemla, A; Zeng, J C; Zeng, Q; Zengel, K; Zenin, O; Ženiš, T; Zerwas, D; Zhang, D; Zhang, F; Zhang, G; Zhang, H; Zhang, J; Zhang, L; Zhang, R; Zhang, X; Zhang, Z; Zhao, X; Zhao, Y; Zhao, Z; Zhemchugov, A; Zhong, J; Zhou, B; Zhou, C; Zhou, L; Zhou, L; Zhou, M; Zhou, N; Zhu, C G; Zhu, H; Zhu, J; Zhu, Y; Zhuang, X; Zhukov, K; Zibell, A; Zieminska, D; Zimine, N I; Zimmermann, C; Zimmermann, S; Zinonos, Z; Zinser, M; Ziolkowski, M; Živković, L; Zobernig, G; Zoccoli, A; Zur Nedden, M; Zurzolo, G; Zwalinski, L

2016-01-01

This paper presents a new method of reconstructing the individual charged and neutral hadrons in tau decays with the ATLAS detector. The reconstructed hadrons are used to classify the decay mode and to calculate the visible four-momentum of reconstructed tau candidates, significantly improving the resolution with respect to the calibration in the existing tau reconstruction. The performance of the reconstruction algorithm is optimised and evaluated using simulation and validated using samples of [Formula: see text] and [Formula: see text]+jets events selected from proton-proton collisions at a centre-of-mass energy [Formula: see text], corresponding to an integrated luminosity of 5 [Formula: see text].

Ultra-long high-sensitivity Φ-OTDR for high spatial resolution intrusion detection of pipelines.

PubMed

Peng, Fei; Wu, Han; Jia, Xin-Hong; Rao, Yun-Jiang; Wang, Zi-Nan; Peng, Zheng-Pu

2014-06-02

An ultra-long phase-sensitive optical time domain reflectometry (Φ-OTDR) that can achieve high-sensitivity intrusion detection over 131.5km fiber with high spatial resolution of 8m is presented, which is the longest Φ-OTDR reported to date, to the best of our knowledge. It is found that the combination of distributed Raman amplification with heterodyne detection can extend the sensing distance and enhances the sensitivity substantially, leading to the realization of ultra-long Φ-OTDR with high sensitivity and spatial resolution. Furthermore, the feasibility of applying such an ultra-long Φ-OTDR to pipeline security monitoring is demonstrated and the features of intrusion signal can be extracted with improved SNR by using the wavelet detrending/denoising method proposed.

Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

NASA Astrophysics Data System (ADS)

Higginson, Drew Pitney

The cone-guided fast ignition approach to Inertial Confinement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets when intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the first time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of Kalpha x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an effective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser

Analysis of trace halocarbon contaminants in ultra high purity helium

NASA Technical Reports Server (NTRS)

Fewell, Larry L.

1994-01-01

This study describes the analysis of ultra high purity helium. Purification studies were conducted and containment removal was effected by the utilization of solid adsorbent purge-trap systems at cryogenic temperatures. Volatile organic compounds in ultra high purity helium were adsorbed on a solid adsorbent-cryogenic trap, and thermally desorbed trace halocarbon and other contaminants were analyzed by combined gas chromatography-mass spectrometry.

Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity

PubMed Central

Stack, Cliona; Jainuddin, Shari; Elipenahli, Ceyhan; Gerges, Meri; Starkova, Natalia; Starkov, Anatoly A.; Jové, Mariona; Portero-Otin, Manuel; Launay, Nathalie; Pujol, Aurora; Kaidery, Navneet Ammal; Thomas, Bobby; Tampellini, Davide; Beal, M. Flint; Dumont, Magali

2014-01-01

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology. PMID:24556215

Near-atomic model of microtubule-tau interactions.

PubMed

Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon; Downing, Kenneth H; DiMaio, Frank; Nogales, Eva

2018-06-15

Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Modulation of Tau Isoforms Imbalance Precludes Tau Pathology and Cognitive Decline in a Mouse Model of Tauopathy.

PubMed

Espíndola, Sonia Lorena; Damianich, Ana; Alvarez, Rodrigo Javier; Sartor, Manuela; Belforte, Juan Emilio; Ferrario, Juan Esteban; Gallo, Jean-Marc; Avale, María Elena

2018-04-17

The microtubule-associated protein tau regulates myriad neuronal functions, such as microtubule dynamics, axonal transport and neurite outgrowth. Tauopathies are neurodegenerative disorders characterized by the abnormal metabolism of tau, which accumulates as insoluble neuronal deposits. The adult human brain contains equal amounts of tau isoforms with three (3R) or four (4R) repeats of microtubule-binding domains, derived from the alternative splicing of exon 10 (E10) in the tau transcript. Several tauopathies are associated with imbalances of tau isoforms, due to splicing deficits. Here, we used a trans-splicing strategy to shift the inclusion of E10 in a mouse model of tauopathy that produces abnormal excess of 3R tau. Modulating the 3R/4R ratio in the prefrontal cortex led to a significant reduction of pathological tau accumulation concomitant with improvement of neuronal firing and reduction of cognitive impairments. Our results suggest promising potential for the use of RNA reprogramming in human neurodegenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Energy deposition processes in biological tissue: nonthermal biohazards seem unlikely in the ultra-high frequency range.

PubMed

Pickard, W F; Moros, E G

2001-02-01

The prospects of ultra high frequency (UHF, 300--3000 MHz) irradiation producing a nonthermal bioeffect are considered theoretically and found to be small. First, a general formula is derived within the framework of macroscopic electrodynamics for the specific absorption rate of microwaves in a biological tissue; this involves the complex Poynting vector, the mass density of the medium, the angular frequency of the electromagnetic field, and the three complex electromagnetic constitutive parameters of the medium. In the frequency ranges used for cellular telephony and personal communication systems, this model predicts that the chief physical loss mechanism will be ionic conduction, with increasingly important contributions from dielectric relaxation as the frequency rises. However, even in a magnetite unit cell within a magnetosome the deposition rate should not exceed 1/10 k(B)T per second. This supports previous arguments for the improbability of biological effects at UHF frequencies unless a mechanism can be found for accumulating energy over time and space and focussing it. Second, three possible nonthermal accumulation mechanisms are then considered and shown to be unlikely: (i) multiphoton absorption processes; (ii) direct electric field effects on ions; (iii) cooperative effects and/or coherent excitations. Finally, it is concluded that the rate of energy deposition from a typical field and within a typical tissue is so small as to make unlikely any significant nonthermal biological effect. Copyright 2001 Wiley-Liss, Inc.

Cubic Calorimeter for High-Energy Electrons in Ultra-Long Ballooning

NASA Technical Reports Server (NTRS)

Moiseev, Alexander A.; Mitchell, John W.; Ormes, Jonathan F.; Streitmatter, Robert E.

2003-01-01

The concept and optimization study of a balloon-borne instrument to study high-energy (from 100 GeV to 5 TeV) cosmic ray electrons will be presented. This energy range of electrons is very interesting for the study of cosmic ray propagation and the search for the nearby sources of high-energy electrons. The instrument is based on a cubic design that allows the detection from all sides. Proton rejection is provided by stringent track analysis, which allows defining when an electron shower is exhausted while the hadron shower continues development. The collecting power of a nominal balloon-borne instrument using this concept will be over 2 square meters sr. This will provide approximately 3,000 electron events above 500 GeV for 3-month long ULDB flight. This instrument will also be capable of detecting sharp features in the high energy gamma-ray spectrum such as gamma-ray lines originating from the dark matter annihilation.

Ultra-low-power conversion and management techniques for thermoelectric energy harvesting applications

NASA Astrophysics Data System (ADS)

Fleming, Jerry W.

2010-04-01

Thermoelectric energy harvesting has increasingly gained acceptance as a potential power source that can be used for numerous commercial and military applications. However, power electronic designers have struggled to incorporate energy harvesting methods into their designs due to the relatively small voltage levels available from many harvesting device technologies. In order to bridge this gap, an ultra-low input voltage power conversion method is needed to convert small amounts of scavenged energy into a usable form of electricity. Such a method would be an enabler for new and improved medical devices, sensor systems, and other portable electronic products. This paper addresses the technical challenges involved in ultra-low-voltage power conversion by providing a solution utilizing novel power conversion techniques and applied technologies. Our solution utilizes intelligent power management techniques to control unknown startup conditions. The load and supply management functionality is also controlled in a deterministic manner. The DC to DC converter input operating voltage is 20mV with a conversion efficiency of 90% or more. The output voltage is stored into a storage device such as an ultra-capacitor or lithium-ion battery for use during brown-out or unfavorable harvesting conditions. Applications requiring modular, low power, extended maintenance cycles, such as wireless instrumentation would significantly benefit from the novel power conversion and harvesting techniques outlined in this paper.

Ultra-High Surface Speed for Metal Removal, Artillery Shell

DTIC Science & Technology

1981-07-01

TECHNICAL LIBRARY "y/a^^cr^ AD-E400 660 CONTRACTOR REPORT ARLCD-CR- 81019 ULTRA-HIGH SURFACE SPEED FOR METAL REMOVAL, ARTILLERY SHELL RICHARD F...Report ARLCD-CR- 81019 2. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4. TITLE (and Subtitle) ULTRA-HIGH SURFACE SPEED FOR METAL...UNIT* tuiPPtO 1 MIL -STD-43CA i, ASTM A-274-64 EF A1SI~1340 SEHI FIN FORGING STEEL 6 RC SQ ■ IP 120093* a LIFTS 38 PCS

Dexmedetomidine Increases Tau Phosphorylation Under Normothermic Conditions In Vivo and In Vitro

PubMed Central

Whittington, Robert A.; Virág, László; Gratuze, Maud; Petry, Franck R.; Noël, Anastasia; Poitras, Isabelle; Truchetti, Geoffrey; Marcouiller, François; Papon, Marie-Amélie; Khoury, Noura El; Wong, Kevin; Bretteville, Alexis; Morin, Françoise; Planel, Emmanuel

2015-01-01

There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have thus been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine, an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to non-transgenic mice, dexmedetomidine induced tau hyperphosphorylation persisting up to 6h in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor (α2-AR) antagonist, blocked dexmedetomidine-induced tau hyperphosphorylation. Furthermore, dexmedetomidine dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze, and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that dexmedetomidine: i) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-AR activation, ii) promotes tau aggregation in a mouse model of tauopathy, and iii) impacts spatial reference memory. PMID:26058840

Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear 2H, 17O and 31P MRS at ultra-high field.

PubMed

Zhu, Xiao-Hong; Lu, Ming; Chen, Wei

2018-07-01

Brain energy metabolism relies predominantly on glucose and oxygen utilization to generate biochemical energy in the form of adenosine triphosphate (ATP). ATP is essential for maintaining basal electrophysiological activities in a resting brain and supporting evoked neuronal activity under an activated state. Studying complex neuroenergetic processes in the brain requires sophisticated neuroimaging techniques enabling noninvasive and quantitative assessment of cerebral energy metabolisms and quantification of metabolic rates. Recent state-of-the-art in vivo X-nuclear MRS techniques, including 2 H, 17 O and 31 P MRS have shown promise, especially at ultra-high fields, in the quest for understanding neuroenergetics and brain function using preclinical models and in human subjects under healthy and diseased conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

TENTATIVE EVIDENCE FOR RELATIVISTIC ELECTRONS GENERATED BY THE JET OF THE YOUNG SUN-LIKE STAR DG Tau

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

Ainsworth, Rachael E.; Ray, Tom P.; Taylor, Andrew M.

2014-09-01

Synchrotron emission has recently been detected in the jet of a massive protostar, providing further evidence that certain jet formation characteristics for young stars are similar to those found for highly relativistic jets from active galactic nuclei. We present data at 325 and 610 MHz taken with the Giant Metrewave Radio Telescope of the young, low-mass star DG Tau, an analog of the Sun soon after its birth. This is the first investigation of a low-mass young stellar object at such low frequencies. We detect emission with a synchrotron spectral index in the proximity of the DG Tau jet and interpretmore » this emission as a prominent bow shock associated with this outflow. This result provides tentative evidence for the acceleration of particles to relativistic energies due to the shock impact of this otherwise very low-power jet against the ambient medium. We calculate the equipartition magnetic field strength B {sub min} ≈ 0.11 mG and particle energy E {sub min} ≈ 4 × 10{sup 40} erg, which are the minimum requirements to account for the synchrotron emission of the DG Tau bow shock. These results suggest the possibility of low energy cosmic rays being generated by young Sun-like stars.« less

An ultra-low power CMOS image sensor with on-chip energy harvesting and power management capability.

PubMed

Cevik, Ismail; Huang, Xiwei; Yu, Hao; Yan, Mei; Ay, Suat U

2015-03-06

An ultra-low power CMOS image sensor with on-chip energy harvesting and power management capability is introduced in this paper. The photodiode pixel array can not only capture images but also harvest solar energy. As such, the CMOS image sensor chip is able to switch between imaging and harvesting modes towards self-power operation. Moreover, an on-chip maximum power point tracking (MPPT)-based power management system (PMS) is designed for the dual-mode image sensor to further improve the energy efficiency. A new isolated P-well energy harvesting and imaging (EHI) pixel with very high fill factor is introduced. Several ultra-low power design techniques such as reset and select boosting techniques have been utilized to maintain a wide pixel dynamic range. The chip was designed and fabricated in a 1.8 V, 1P6M 0.18 µm CMOS process. Total power consumption of the imager is 6.53 µW for a 96 × 96 pixel array with 1 V supply and 5 fps frame rate. Up to 30 μW of power could be generated by the new EHI pixels. The PMS is capable of providing 3× the power required during imaging mode with 50% efficiency allowing energy autonomous operation with a 72.5% duty cycle.

An Ultra-Low Power CMOS Image Sensor with On-Chip Energy Harvesting and Power Management Capability

PubMed Central

Cevik, Ismail; Huang, Xiwei; Yu, Hao; Yan, Mei; Ay, Suat U.

2015-01-01

An ultra-low power CMOS image sensor with on-chip energy harvesting and power management capability is introduced in this paper. The photodiode pixel array can not only capture images but also harvest solar energy. As such, the CMOS image sensor chip is able to switch between imaging and harvesting modes towards self-power operation. Moreover, an on-chip maximum power point tracking (MPPT)-based power management system (PMS) is designed for the dual-mode image sensor to further improve the energy efficiency. A new isolated P-well energy harvesting and imaging (EHI) pixel with very high fill factor is introduced. Several ultra-low power design techniques such as reset and select boosting techniques have been utilized to maintain a wide pixel dynamic range. The chip was designed and fabricated in a 1.8 V, 1P6M 0.18 µm CMOS process. Total power consumption of the imager is 6.53 µW for a 96 × 96 pixel array with 1 V supply and 5 fps frame rate. Up to 30 μW of power could be generated by the new EHI pixels. The PMS is capable of providing 3× the power required during imaging mode with 50% efficiency allowing energy autonomous operation with a 72.5% duty cycle. PMID:25756863

Ultra-Capacitor Energy Storage in a Large Hybrid Electric Bus

NASA Technical Reports Server (NTRS)

Viterna, L. A.

1997-01-01

The power requirements for inner city transit buses are characterized by power peaks about an order of magnitude larger than the average power usage of the vehicle. For these vehicles, hybrid power trains can offer significantly improved fuel economy and exhaust emissions. A critical design challenge, however, has been developing the energy storage and power management system to respond to these rapid power variations. Most hybrid vehicles today use chemical energy storage batteries to supplement the power from the fuel burning generator unit. Chemical storage batteries however, present several difficulties in power management and control. These difficulties include (1) inadequate life, (2) limited current delivery as well as absorption during regenerative braking, (3) inaccurate measurement of state of charge, and (4) stored energy safety issues. Recent advances in ultra-capacitor technology create an opportunity to address these concerns. The NASA Lewis Research Center, in cooperation with industry and academia, has developed an advanced hybrid electric transit bus using ultra-capacitors as the primary energy storage system. At over 15,000-kg gross weight, this is the largest vehicle of its kind ever built using this advanced energy storage technology. Results of analyses show that the vehicle will match the performance of an equivalent conventionally powered vehicle over typical inner city drive cycles. This paper describes the overall power system architecture, the evolution of the control strategy, and analysis of power flow and vehicle performance.

Ultra-low noise supercontinuum source for ultra-high resolution optical coherence tomography at 1300 nm

NASA Astrophysics Data System (ADS)

Gonzalo, I. B.; Maria, M.; Engelsholm, R. D.; Feuchter, T.; Leick, L.; Moselund, P. M.; Podoleanu, A.; Bang, O.

2018-02-01

Supercontinuum (SC) sources are of great interest for many applications due to their ultra-broad optical bandwidth, good beam quality and high power spectral density [1]. In particular, the high average power over large bandwidths makes SC light sources excellent candidates for ultra-high resolution optical coherence tomography (UHR-OCT) [2-5]. However, conventional SC sources suffer from high pulse-to-pulse intensity fluctuations as a result of the noise-sensitive nonlinear effects involved in the SC generation process [6-9]. This intensity noise from the SC source can limit the performance of OCT, resulting in a reduced signal-to-noise ratio (SNR) [10-12]. Much work has been done to reduce the noise of the SC sources for instance with fiber tapers [7,8] or increasing the repetition rate of the pump laser for averaging in the spectrometer [10,12]. An alternative approach is to use all-normal dispersion (ANDi) fibers [13,14] to generate SC light from well-known coherent nonlinear processes [15-17]. In fact, reduction of SC noise using ANDi fibers compared to anomalous dispersion SC pumped by sub-picosecond pulses has been recently demonstrated [18], but a cladding mode was used to stabilize the ANDi SC. In this work, we characterize the noise performance of a femtosecond pumped ANDi based SC and a commercial SC source in an UHR-OCT system at 1300 nm. We show that the ANDi based SC presents exceptional noise properties compared to a commercial source. An improvement of 5 dB in SNR is measured in the UHR-OCT system, and the noise behavior resembles that of a superluminiscent diode. This preliminary study is a step forward towards development of an ultra-low noise SC source at 1300 nm for ultra-high resolution OCT.

Ultra-Deep Drilling Cost Reduction; Design and Fabrication of an Ultra-Deep Drilling Simulator (UDS)

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

Lindstrom, Jason

2010-01-31

Ultra-deep drilling, below about 20,000 ft (6,096 m), is extremely expensive and limits the recovery of hydrocarbons at these depths. Unfortunately, rock breakage and cuttings removal under these conditions is not understood. To better understand and thus reduce cost at these conditions an ultra-deep single cutter drilling simulator (UDS) capable of drill cutter and mud tests to sustained pressure and temperature of 30,000 psi (207 MPa) and 482 °F (250 °C), respectively, was designed and manufactured at TerraTek, a Schlumberger company, in cooperation with the Department of Energy’s National Energy Technology Laboratory. UDS testing under ultra-deep drilling conditions offers anmore » economical alternative to high day rates and can prove or disprove the viability of a particular drilling technique or fluid to provide opportunity for future domestic energy needs.« less

Volumetric Heating of Ultra-High Energy Density Relativistic Plasmas by Ultrafast Laser Irradiation of Aligned Nanowire Arrays

NASA Astrophysics Data System (ADS)

Bargsten, Clayton; Hollinger, Reed; Shlyaptsev, Vyacheslav; Pukhov, Alexander; Keiss, David; Townsend, Amanda; Wang, Yong; Wang, Shoujun; Prieto, Amy; Rocca, Jorge

2014-10-01

We have demonstrated the volumetric heating of near-solid density plasmas to keV temperatures by ultra-high contrast femtosecond laser irradiation of arrays of vertically aligned nanowires with an average density up to 30% solid density. X-ray spectra show that irradiation of Ni and Au nanowire arrays with laser pulses of relativistic intensities ionizes plasma volumes several micrometers in depth to the He-like and Co-like (Au 52 +) stages respectively. The penetration depth of the heat into the nanowire array was measured monitoring He-like Co lines from irradiated arrays in which the nanowires are composed of a Co segment buried under a selected length of Ni. The measurement shows the ionization reaches He-like Co for depth of up to 5 μm within the target. This volumetric plasma heating approach creates a new laboratory plasma regime in which extreme plasma parameters can be accessed with table-top lasers. Scaling to higher laser intensities promises to create plasmas with temperatures and pressures approaching those in the center of the sun. Work supported by the U.S Department of Energy, Fusion Energy Sciences and the Defense Threat Reduction Agency grant HDTRA-1-10-1-0079. A.P was supported by of DFG-funded project TR18.

Mid-infrared ultra-high-Q resonators based on fluoride crystalline materials

NASA Astrophysics Data System (ADS)

Lecaplain, C.; Javerzac-Galy, C.; Gorodetsky, M. L.; Kippenberg, T. J.

2016-11-01

The unavailability of highly transparent materials in the mid-infrared has been the main limitation in the development of ultra-sensitive molecular sensors or cavity-based spectroscopy applications. Whispering gallery mode microresonators have attained ultra-high-quality (Q) factor resonances in the near-infrared and visible. Here we report ultra-high Q factors in the mid-infrared using polished alkaline earth metal fluoride crystals. Using an uncoated chalcogenide tapered fibre as a high-ideality coupler in the mid-infrared, we study via cavity ringdown technique the losses of BaF2, CaF2, MgF2 and SrF2 microresonators. We show that MgF2 is limited by multiphonon absorption by studying the temperature dependence of the Q factor. In contrast, in SrF2 and BaF2 the lower multiphonon absorption leads to ultra-high Q factors at 4.5 μm. These values correspond to an optical finesse of , the highest value achieved for any type of mid-infrared resonator to date.

Mid-infrared ultra-high-Q resonators based on fluoride crystalline materials

PubMed Central

Lecaplain, C.; Javerzac-Galy, C.; Gorodetsky, M. L.; Kippenberg, T. J.

2016-01-01

The unavailability of highly transparent materials in the mid-infrared has been the main limitation in the development of ultra-sensitive molecular sensors or cavity-based spectroscopy applications. Whispering gallery mode microresonators have attained ultra-high-quality (Q) factor resonances in the near-infrared and visible. Here we report ultra-high Q factors in the mid-infrared using polished alkaline earth metal fluoride crystals. Using an uncoated chalcogenide tapered fibre as a high-ideality coupler in the mid-infrared, we study via cavity ringdown technique the losses of BaF2, CaF2, MgF2 and SrF2 microresonators. We show that MgF2 is limited by multiphonon absorption by studying the temperature dependence of the Q factor. In contrast, in SrF2 and BaF2 the lower multiphonon absorption leads to ultra-high Q factors at 4.5 μm. These values correspond to an optical finesse of , the highest value achieved for any type of mid-infrared resonator to date. PMID:27869119

Mid-infrared ultra-high-Q resonators based on fluoride crystalline materials.

PubMed

Lecaplain, C; Javerzac-Galy, C; Gorodetsky, M L; Kippenberg, T J

2016-11-21

The unavailability of highly transparent materials in the mid-infrared has been the main limitation in the development of ultra-sensitive molecular sensors or cavity-based spectroscopy applications. Whispering gallery mode microresonators have attained ultra-high-quality (Q) factor resonances in the near-infrared and visible. Here we report ultra-high Q factors in the mid-infrared using polished alkaline earth metal fluoride crystals. Using an uncoated chalcogenide tapered fibre as a high-ideality coupler in the mid-infrared, we study via cavity ringdown technique the losses of BaF 2 , CaF 2 , MgF 2 and SrF 2 microresonators. We show that MgF 2 is limited by multiphonon absorption by studying the temperature dependence of the Q factor. In contrast, in SrF 2 and BaF 2 the lower multiphonon absorption leads to ultra-high Q factors at 4.5 μm. These values correspond to an optical finesse of , the highest value achieved for any type of mid-infrared resonator to date.

Search for Point Sources of High Energy Neutrinos with Final Data from AMANDA-II

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

IceCube Collaboration; Klein, Spencer

2009-03-06

We present a search for point sources of high energy neutrinos using 3.8 years of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the Northern Sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E{sup -2} neutrino fluxes from points in the Northern Sky, with an average upper limit of E{supmore » 2}{Phi}{sub {nu}{sub {mu}}+{nu}{sub {tau}}} {le} 5.2 x 10{sup -11} TeV cm{sup -2} s{sup -1} on the sum of {nu}{sub {mu}} and {nu}{sub {tau}} fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.« less

Search for point sources of high energy neutrinos with final data from AMANDA-II

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

Abbasi, R.; Andeen, K.; Baker, M.

2009-03-15

We present a search for point sources of high energy neutrinos using 3.8 yr of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the northern sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E{sup -2} neutrino fluxes from points in the northern sky, with an average upper limit of E{supmore » 2}{phi}{sub {nu}{sub {mu}}}{sub +{nu}{sub {tau}}}{<=}5.2x10{sup -11} TeV cm{sup -2} s{sup -1} on the sum of {nu}{sub {mu}} and {nu}{sub {tau}} fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.« less

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease.

PubMed

Steen Jensen, Camilla; Portelius, Erik; Siersma, Volkert; Høgh, Peter; Wermuth, Lene; Blennow, Kaj; Zetterberg, Henrik; Waldemar, Gunhild; Gregers Hasselbalch, Steen; Hviid Simonsen, Anja

2016-01-01

Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway. From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aβ species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype. We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype. Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aβ, t-tau, p-tau and sAPP species. © 2016 S. Karger AG, Basel.

Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies

PubMed Central

Kontaxi, Christiana; Piccardo, Pedro; Gill, Andrew C.

2017-01-01

Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an “unfolded” conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions. PMID:28848737

Tau regulates the subcellular localization of calmodulin

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

Barreda, Elena Gomez de; Avila, Jesus, E-mail: javila@cbm.uam.es; CIBER de Enfermedades Neurodegenerativas, 28031 Madrid

Highlights: {yields} In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in amore » change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.« less

Toward high-energy-density, high-efficiency, and moderate-temperature chip-scale thermophotovoltaics

PubMed Central

Chan, Walker R.; Bermel, Peter; Pilawa-Podgurski, Robert C. N.; Marton, Christopher H.; Jensen, Klavs F.; Senkevich, Jay J.; Joannopoulos, John D.; Soljačić, Marin; Celanovic, Ivan

2013-01-01

The challenging problem of ultra-high-energy-density, high-efficiency, and small-scale portable power generation is addressed here using a distinctive thermophotovoltaic energy conversion mechanism and chip-based system design, which we name the microthermophotovoltaic (μTPV) generator. The approach is predicted to be capable of up to 32% efficient heat-to-electricity conversion within a millimeter-scale form factor. Although considerable technological barriers need to be overcome to reach full performance, we have performed a robust experimental demonstration that validates the theoretical framework and the key system components. Even with a much-simplified μTPV system design with theoretical efficiency prediction of 2.7%, we experimentally demonstrate 2.5% efficiency. The μTPV experimental system that was built and tested comprises a silicon propane microcombustor, an integrated high-temperature photonic crystal selective thermal emitter, four 0.55-eV GaInAsSb thermophotovoltaic diodes, and an ultra-high-efficiency maximum power-point tracking power electronics converter. The system was demonstrated to operate up to 800 °C (silicon microcombustor temperature) with an input thermal power of 13.7 W, generating 344 mW of electric power over a 1-cm2 area. PMID:23440220

Design Method For Ultra-High Resolution Linear CCD Imagers

NASA Astrophysics Data System (ADS)

Sheu, Larry S.; Truong, Thanh; Yuzuki, Larry; Elhatem, Abdul; Kadekodi, Narayan

1984-11-01

This paper presents the design method to achieve ultra-high resolution linear imagers. This method utilizes advanced design rules and novel staggered bilinear photo sensor arrays with quadrilinear shift registers. Design constraint in the detector arrays and shift registers are analyzed. Imager architecture to achieve ultra-high resolution is presented. The characteristics of MTF, aliasing, speed, transfer efficiency and fine photolithography requirements associated with this architecture are also discussed. A CCD imager with advanced 1.5 um minimum feature size was fabricated. It is intended as a test vehicle for the next generation small sampling pitch ultra-high resolution CCD imager. Standard double-poly, two-phase shift registers were fabricated at an 8 um pitch using the advanced design rules. A special process step that blocked the source-drain implant from the shift register area was invented. This guaranteed excellent performance of the shift registers regardless of the small poly overlaps. A charge transfer efficiency of better than 0.99995 and maximum transfer speed of 8 MHz were achieved. The imager showed excellent performance. The dark current was less than 0.2 mV/ms, saturation 250 mV, adjacent photoresponse non-uniformity ± 4% and responsivity 0.7 V/ μJ/cm2 for the 8 μm x 6 μm photosensor size. The MTF was 0.6 at 62.5 cycles/mm. These results confirm the feasibility of the next generation ultra-high resolution CCD imagers.

Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

PubMed

Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

2016-01-01

Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights

Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy

PubMed Central

Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K.; Bernick, Charles; Ghosh, Chaitali; Bazarian, Jeffrey J.; Janigro, Damir

2016-01-01

Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

Precision optical slit for high heat load or ultra high vacuum

DOEpatents

Andresen, Nord C.; DiGennaro, Richard S.; Swain, Thomas L.

1995-01-01

This invention relates generally to slits used in optics that must be precisely aligned and adjusted. The optical slits of the present invention are useful in x-ray optics, x-ray beam lines, optical systems in which the entrance slit is critical for high wavelength resolution. The invention is particularly useful in ultra high vacuum systems where lubricants are difficult to use and designs which avoid the movement of metal parts against one another are important, such as monochrometers for high wavelength resolution with ultra high vacuum systems. The invention further relates to optical systems in which temperature characteristics of the slit materials is important. The present invention yet additionally relates to precision slits wherein the opposing edges of the slit must be precisely moved relative to a center line between the edges with each edge retaining its parallel orientation with respect to the other edge and/or the center line.

77 FR 59182 - Ultra-Deepwater Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... DEPARTMENT OF ENERGY Ultra-Deepwater Advisory Committee AGENCY: Office of Fossil Energy... of the Ultra-Deepwater Advisory Committee is to provide advice on development and implementation of programs related to ultra-deepwater architecture and technology to the Secretary of Energy and provide...

Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity.

PubMed

Stack, Cliona; Jainuddin, Shari; Elipenahli, Ceyhan; Gerges, Meri; Starkova, Natalia; Starkov, Anatoly A; Jové, Mariona; Portero-Otin, Manuel; Launay, Nathalie; Pujol, Aurora; Kaidery, Navneet Ammal; Thomas, Bobby; Tampellini, Davide; Beal, M Flint; Dumont, Magali

2014-07-15

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

76 FR 77990 - Ultra-Deepwater Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... DEPARTMENT OF ENERGY Ultra-Deepwater Advisory Committee AGENCY: Office of Fossil Energy... Committee: The purpose of the Ultra-Deepwater Advisory Committee is to provide advice to the Secretary of Energy on development and implementation of programs related to ultra-deepwater natural gas and other...

76 FR 6775 - Ultra-Deepwater Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-08

... DEPARTMENT OF ENERGY Ultra-Deepwater Advisory Committee AGENCY: Department of Energy, Office of... Committee: The purpose of the Ultra-Deepwater Advisory Committee is to provide advice on development and implementation of programs related to ultra-deepwater architecture and technology to the Secretary of Energy and...

The life cycle of infrared ultra-short high intensity laser pulses in air

NASA Astrophysics Data System (ADS)

Ma, Cunliang; Lin, Wenbin

2015-08-01

The life cycle of ultra-short high intensity laser pulses propagation in air is studied. As the controversial of the high-order Kerr indices measured by Loriot et al. [Opt. Express 18, 3011 (2010)], we focus on two models which are high-order Kerr effect included and not included. Two factors are mainly analyzed, group-velocity-dispersion and the energy evolution of the pulse. It is found that the group-velocity-dispersion can not be simply ignored even though the pulse's duration is as long as several hundreds femtoseconds. The energy loss due to the multi-photon-absorption is very small, and it may hardly change the propagation length of the pulse. Another contribution of this work is to introduce a probability quantity, which may be useful in validating the positive and negative alternating of the Kerr and high-order Kerr indices.

Fast Spectroscopic Imaging and Field Compensation Using Frequency Modulation at Ultra-High-Field

NASA Astrophysics Data System (ADS)

Jang, Albert Woo Ju

The high energy phosphates (HEP) in the myocardium, which are critical to understanding the cardiac function in both normal and pathophysiologic states, can be assessed non-invasively in vivo using phosphorus-31 (31P) spectroscopy. Compared to proton, for the same volume and magnetic field strength, the available signal-to-noise (SNR) ratio of the HEP metabolites is orders of magnitude lower mainly due to its intrinsically low concentration. Hence, cardiac spectroscopy greatly benefits when performed at ultra-high-fields (UHF, ≥ 7 T), both in terms of increased SNR and increased spectroscopic resolution. However, at ultra-high-field strengths, complications arise from the RF transmit wavelength becoming comparable or smaller than the field-of-view (FOV), thus exhibiting wave-like behavior. Furthermore, even with the spectroscopic resolution afforded at UHF, measuring myocardial inorganic phosphate (Pi) is still a challenge and has been a major barrier in extracting the ATP turnover rate. Recently, an indirect way of extracting the ATP hydrolysis rate forgoing direct measurement of Pi was established. In this work, we combine this method with the T1 nom method to monitor the transmural distribution of forward creatine kinase reaction (kf,CK) and ATP hydrolysis rate (kr,ATPase) of the myocardium, effectively reducing data acquisition time by up to an order of magnitude. In addition, a new class of 2D FM pulses and multidimensional adiabatic pulses are presented, which can compensate for B1 inhomogeneity through its spatiotemporal properties. These pulses should be valuable for spectroscopic applications at ultra-high-fields.

Determination of the proton-to-helium ratio in cosmic rays at ultra-high energies from the tail of the Xmax distribution

NASA Astrophysics Data System (ADS)

Yushkov, A.; Risse, M.; Werner, M.; Krieg, J.

2016-12-01

We present a method to determine the proton-to-helium ratio in cosmic rays at ultra-high energies. It makes use of the exponential slope, Λ, of the tail of the Xmax distribution measured by an air shower experiment. The method is quite robust with respect to uncertainties from modeling hadronic interactions and to systematic errors on Xmax and energy, and to the possible presence of primary nuclei heavier than helium. Obtaining the proton-to-helium ratio with air shower experiments would be a remarkable achievement. To quantify the applicability of a particular mass-sensitive variable for mass composition analysis despite hadronic uncertainties we introduce as a metric the 'analysis indicator' and find an improved performance of the Λ method compared to other variables currently used in the literature. The fraction of events in the tail of the Xmax distribution can provide additional information on the presence of nuclei heavier than helium in the primary beam.

Energy Balance of Triathletes during an Ultra-Endurance Event

PubMed Central

Barrero, Anna; Erola, Pau; Bescós, Raúl

2014-01-01

The nutritional strategy during an ultra-endurance triathlon (UET) is one of the main concerns of athletes competing in such events. The purpose of this study is to provide a proper characterization of the energy and fluid intake during real competition in male triathletes during a complete UET and to estimate the energy expenditure (EE) and the fluid balance through the race. Methods: Eleven triathletes performed a UET. All food and drinks ingested during the race were weighed and recorded in order to assess the energy intake (EI) during the race. The EE was estimated from heart rate (HR) recordings during the race, using the individual HR-oxygen uptake (Vo2) regressions developed from three incremental tests on the 50-m swimming pool, cycle ergometer, and running treadmill. Additionally, body mass (BM), total body water (TBW) and intracellular (ICW) and extracellular water (ECW) were assessed before and after the race using a multifrequency bioimpedance device (BIA). Results: Mean competition time and HR was 755 ± 69 min and 137 ± 6 beats/min, respectively. Mean EI was 3643 ± 1219 kcal and the estimated EE was 11,009 ± 664 kcal. Consequently, athletes showed an energy deficit of 7365 ± 1286 kcal (66.9% ± 11.7%). BM decreased significantly after the race and significant losses of TBW were found. Such losses were more related to a reduction of extracellular fluids than intracellular fluids. Conclusions: Our results confirm the high energy demands of UET races, which are not compensated by nutrient and fluid intake, resulting in a large energy deficit. PMID:25558906

Energy balance of triathletes during an ultra-endurance event.

PubMed

Barrero, Anna; Erola, Pau; Bescós, Raúl

2014-12-31

The nutritional strategy during an ultra-endurance triathlon (UET) is one of the main concerns of athletes competing in such events. The purpose of this study is to provide a proper characterization of the energy and fluid intake during real competition in male triathletes during a complete UET and to estimate the energy expenditure (EE) and the fluid balance through the race. Eleven triathletes performed a UET. All food and drinks ingested during the race were weighed and recorded in order to assess the energy intake (EI) during the race. The EE was estimated from heart rate (HR) recordings during the race, using the individual HR-oxygen uptake (Vo2) regressions developed from three incremental tests on the 50-m swimming pool, cycle ergometer, and running treadmill. Additionally, body mass (BM), total body water (TBW) and intracellular (ICW) and extracellular water (ECW) were assessed before and after the race using a multifrequency bioimpedance device (BIA). Mean competition time and HR was 755 ± 69 min and 137 ± 6 beats/min, respectively. Mean EI was 3643 ± 1219 kcal and the estimated EE was 11,009 ± 664 kcal. Consequently, athletes showed an energy deficit of 7365 ± 1286 kcal (66.9% ± 11.7%). BM decreased significantly after the race and significant losses of TBW were found. Such losses were more related to a reduction of extracellular fluids than intracellular fluids. Our results confirm the high energy demands of UET races, which are not compensated by nutrient and fluid intake, resulting in a large energy deficit.

Quantum mechanical energy-based screening of combinatorially generated library of tautomers. TauTGen: a tautomer generator program.

PubMed

Harańczyk, Maciej; Gutowski, Maciej

2007-01-01

We describe a procedure of finding low-energy tautomers of a molecule. The procedure consists of (i) combinatorial generation of a library of tautomers, (ii) screening based on the results of geometry optimization of initial structures performed at the density functional level of theory, and (iii) final refinement of geometry for the top hits at the second-order Möller-Plesset level of theory followed by single-point energy calculations at the coupled cluster level of theory with single, double, and perturbative triple excitations. The library of initial structures of various tautomers is generated with TauTGen, a tautomer generator program. The procedure proved to be successful for these molecular systems for which common chemical knowledge had not been sufficient to predict the most stable structures.

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

PubMed Central

2011-01-01

Introduction Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. Methods MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Results Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Conclusions Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy. PMID:21888627

Precision optical slit for high heat load or ultra high vacuum

DOEpatents

Andresen, N.C.; DiGennaro, R.S.; Swain, T.L.

1995-01-24

This invention relates generally to slits used in optics that must be precisely aligned and adjusted. The optical slits of the present invention are useful in x-ray optics, x-ray beam lines, optical systems in which the entrance slit is critical for high wavelength resolution. The invention is particularly useful in ultra high vacuum systems where lubricants are difficult to use and designs which avoid the movement of metal parts against one another are important, such as monochromators for high wavelength resolution with ultra high vacuum systems. The invention further relates to optical systems in which temperature characteristics of the slit materials is important. The present invention yet additionally relates to precision slits wherein the opposing edges of the slit must be precisely moved relative to a center line between the edges with each edge retaining its parallel orientation with respect to the other edge and/or the center line. 21 figures.

Isoprenoids and tau pathology in sporadic Alzheimer's disease.

PubMed

Pelleieux, Sandra; Picard, Cynthia; Lamarre-Théroux, Louise; Dea, Doris; Leduc, Valérie; Tsantrizos, Youla S; Poirier, Judes

2018-05-01

The mevalonate pathway has been described to play a key role in Alzheimer's disease (AD) physiopathology. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are nonsterol isoprenoids derived from mevalonate, which serve as precursors to numerous human metabolites. They facilitate protein prenylation; hFPP and hGGPP synthases act as gateway enzymes to the prenylation of the small guanosine triphosphate (GTP)ase proteins such as RhoA and cdc42 that have been shown to facilitate phospho-tau (p-Tau, i.e., protein tau phosphorylated) production in the brain. In this study, a significant positive correlation was observed between the synthases mRNA prevalence and disease status (FPPS, p < 0.001, n = 123; GGPPS, p < 0.001, n = 122). The levels of mRNA for hFPPS and hGGPPS were found to significantly correlate with the amount of p-Tau protein levels (p < 0.05, n = 34) and neurofibrillary tangle density (p < 0.05, n = 39) in the frontal cortex. Interestingly, high levels of hFPPS and hGGPPS mRNA prevalence are associated with earlier age of onset in AD (p < 0.05, n = 58). Together, these results suggest that accumulation of p-Tau in the AD brain is related, at least in part, to increased levels of neuronal isoprenoids. Copyright © 2018 Elsevier Inc. All rights reserved.

High-Resolution Near-Infrared Polarimetry of a Circumstellar Disk around UX Tau A

NASA Technical Reports Server (NTRS)

Serabyn, G.; Grady, C. A.; Currie, T.

2012-01-01

We present H-band polarimetric imagery of UX Tau A taken with HiCIAO/AO188 on the Subaru Telescope. UX Tau A has been classified as a pre-transitional disk object, with a gap structure separating its inner and outer disks. Our imagery taken with the 0.15" (21 AU) radius coronagraphic mask has revealed a strongly polarized circumstellar disk surrounding UX Tau A which extends to 120 AU, at a spatial resolution of 0.1" (14 AU). It is inclined by 46 degrees plus or minus 2 degrees as the west side is nearest. Although SED modeling and sub-millimeter imagery suggested the presence of a gap in the disk, with the inner edge of the outer disk estimated to be located at 25 - 30 AU, we detect no evidence of a gap at the limit of our inner working angle (23AU) at the near-infrared wavelength. We attribute the observed strong polarization (up to 66 %) to light scattering by dust grains in the disk. However, neither polarization models of the circumstellar disk based on Rayleigh scattering nor Mie scattering approximations were consistent with the observed azimuthal profile of the polarization degrees of the disk. Instead, a geometric optics model of the disk with nonspherical grains with the radii of 30 micrometers is consistent with the observed profile. We suggest that the dust grains have experienced frequent collisional coagulations and have grown in the circumstellar disk of UX Tau A.

High-Resolution Near-Infrared Polarimetry of a Circumstellar Disk around UX Tau A

NASA Astrophysics Data System (ADS)

Tanii, Ryoko; Itoh, Yoichi; Kudo, Tomoyuki; Hioki, Tomonori; Oasa, Yumiko; Gupta, Ranjan; Sen, Asoke K.; Wisniewski, John P.; Muto, Takayuki; Grady, Carol A.; Hashimoto, Jun; Fukagawa, Misato; Mayama, Satoshi; Hornbeck, Jeremy; Sitko, Michael L.; Russell, Ray W.; Werren, Chelsea; Curé, Michel; Currie, Thayne; Ohashi, Nagayoshi; Okamoto, Yoshiko; Momose, Munetake; Honda, Mitsuhiko; Inutsuka, Shu-ichi; Takeuchi, Taku; Dong, Ruobing; Abe, Lyu; Brandner, Wolfgang; Brandt, Timothy D.; Carson, Joseph; Egner, Sebastian E.; Feldt, Markus; Fukue, Tsubasa; Goto, Miwa; Guyon, Olivier; Hayano, Yutaka; Hayashi, Masahiko; Hayashi, Saeko S.; Henning, Thomas; Hodapp, Klaus W.; Ishii, Miki; Iye, Masanori; Janson, Markus; Kandori, Ryo; Knapp, Gillian R.; Kusakabe, Nobuhiko; Kuzuhara, Masayuki; Matsuo, Taro; McElwain, Michael W.; Miyama, Shoken; Morino, Jun-ichi; Moro-Martín, Amaya; Nishimura, Tetsuro; Pyo, Tae-Soo; Serabyn, Eugene; Suto, Hiroshi; Suzuki, Ryuji; Takami, Michihiro; Takato, Naruhisa; Terada, Hiroshi; Thalmann, Christian; Tomono, Daigo; Turner, Edwin L.; Watanabe, Makoto; Yamada, Toru; Takami, Hideki; Usuda, Tomonori; Tamura, Motohide

2012-12-01

We present H-band polarimetric imagery of UX Tau A taken with HiCIAO/AO188 on the Subaru Telescope. UX Tau A has been classified as a pre-transitional disk object, with a gap structure separating its inner and outer disks. Our imagery taken with the 0.''15 (21 AU) radius coronagraphic mask has revealed a strongly polarized circumstellar disk surrounding UX Tau A, which extends to 120 AU, at a spatial resolution of 0.''1 (14 AU). It is inclined by 46° ± 2°, since the west side is nearest. Although SED modeling and sub-millimeter imagery have suggested the presence of a gap in the disk, with the inner edge of the outer disk estimated to be located at 25-30 AU, we detect no evidence of a gap at the limit of our inner working angle (23 AU) at the near-infrared wavelength. We attribute the observed strong polarization (up to 66%) to light scattering by dust grains in the disk. However, neither polarization models of the circumstellar disk based on Rayleigh-scattering nor Mie-scattering approximations were consistent with the observed azimuthal profile of the polarization degrees of the disk. Instead, a geometric optics model of the disk with nonspherical grains with radii of 30μm is consistent with the observed profile. We suggest that the dust grains have experienced frequent collisional coagulations, and have grown in the circumstellar disk of UX Tau A.

Insulin dysfunction and Tau pathology.

PubMed

El Khoury, Noura B; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2014-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

Insulin dysfunction and Tau pathology

PubMed Central

El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2013-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

Evidence for the 125 GeV Higgs boson decaying to a pair of $$\\tau$$ leptons

DOE PAGES

Chatrchyan, Serguei

2014-01-20

A search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012. The dataset corresponds to an integrated luminosity of 4.9 inverse femtobarns at a centre-of-mass energy of 7 TeV and 19.7 inverse femtobarns at 8 TeV. Each tau lepton decays hadronically or leptonically to an electron or a muon, leading to six different final states for the tau-lepton pair, all considered in this analysis. An excess of events is observed over the expected background contributions, with a local significance largermore » than 3 standard deviations for m[H] values between 115 and 130 GeV. The best fit of the observed H to tau tau signal cross section for m[H] = 125 GeV is 0.78 +- 0.27 times the standard model expectation. These observations constitute evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons.« less

Ultra-high strain in epitaxial silicon carbide nanostructures utilizing residual stress amplification

NASA Astrophysics Data System (ADS)

Phan, Hoang-Phuong; Nguyen, Tuan-Khoa; Dinh, Toan; Ina, Ginnosuke; Kermany, Atieh Ranjbar; Qamar, Afzaal; Han, Jisheng; Namazu, Takahiro; Maeda, Ryutaro; Dao, Dzung Viet; Nguyen, Nam-Trung

2017-04-01

Strain engineering has attracted great attention, particularly for epitaxial films grown on a different substrate. Residual strains of SiC have been widely employed to form ultra-high frequency and high Q factor resonators. However, to date, the highest residual strain of SiC was reported to be limited to approximately 0.6%. Large strains induced into SiC could lead to several interesting physical phenomena, as well as significant improvement of resonant frequencies. We report an unprecedented nanostrain-amplifier structure with an ultra-high residual strain up to 8% utilizing the natural residual stress between epitaxial 3C-SiC and Si. In addition, the applied strain can be tuned by changing the dimensions of the amplifier structure. The possibility of introducing such a controllable and ultra-high strain will open the door to investigating the physics of SiC in large strain regimes and the development of ultra sensitive mechanical sensors.

Design And Development Of An Autonomous Radar Receiver For The Detection Of Ultra High Energy Cosmic Rays

NASA Astrophysics Data System (ADS)

Kunwar, Samridha

The detection of ultra-high energy cosmic rays is constrained by their flux, requiring detectors with apertures of hundreds or even thousands of square kilometers and close to one hundred percent duty cycle. The sheer scale that would be required of conventional detectors, to acquire sufficient statistics for energy, composition or anisotropy studies, means that new techniques that reduce manpower and financial resources are continually being sought. In this dissertation, the development of a remote sensing technique based observatory known as bistatic radar, which aims to achieve extensive coverage of the Earth's surface, cf. Telescope Array's 700 km2 surface detector, is discussed. Construction of the radar projects transmitter station was completed in the summer of 2013, and remote receiver stations were deployed in June and November of 2014. These stations accomplish radar echo detection using an analog signal chain. Subject to less radio interference, the remote stations add stereoscopic measurement capabilities that theoretically allow unique determination of cosmic ray geometry and core location. An FPGA is used as a distributed data processing node within the project. The FPGA provides triggering logic for data sampled at 200 MSa/s, detecting Cosmic Ray shower echoes chirping at -1 to -10 Megahertz/microsecond (depending on the geometry) for several microseconds. The data acquisition system with low power consumption at a cost that is also comparatively inexpensive is described herein.

FDG metabolism associated with tau-amyloid interaction predicts memory decline

PubMed Central

Hanseeuw, Bernard J.; Betensky, Rebecca A.; Schultz, Aaron P.; Papp, Kate V.; Mormino, Elizabeth C.; Sepulcre, Jorge; Bark, John S.; Cosio, Danielle M.; LaPoint, Molly; Chhatwal, Jasmeer P.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith

2017-01-01

Objective To evaluate in normal older adults and preclinical Alzheimer’s disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. Methods We acquired positron emission tomography using F18 Flortaucipir (tau), C11 Pittsburgh Compound B (amyloid) and F18 Fluorodeoxyglucose in 90 clinically normal elderly of the Harvard Aging Brain Study. Results Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly. In contrast, frontal hypometabolism related to the common age-related entorhinal tauopathy, but this dysfunction was independent of amyloid, and did not predict significant memory decline. Neocortical tauopathy was positively associated with metabolism in individuals with sub-threshold amyloid, suggesting that glucose metabolism increases before decreasing in the course of preclinical AD. Interpretation Our study identified a synergistic effect of amyloid and tau deposits and demonstrated for the first time in normal elderly its link to AD-like hypometabolism and to AD-like memory decline. The amyloid effect was seen with tau in neocortex, but not with tau in entorhinal cortex, which is the common site of age-related tauopathy. Entorhinal tau was associated with frontal hypometabolism, but this dysfunction was not associated with memory loss. PMID:28253546

An ultra-high vacuum scanning tunneling microscope operating at sub-Kelvin temperatures and high magnetic fields for spin-resolved measurements

NASA Astrophysics Data System (ADS)

Salazar, C.; Baumann, D.; Hänke, T.; Scheffler, M.; Kühne, T.; Kaiser, M.; Voigtländer, R.; Lindackers, D.; Büchner, B.; Hess, C.

2018-06-01

We present the construction and performance of an ultra-low-temperature scanning tunneling microscope (STM), working in ultra-high vacuum (UHV) conditions and in high magnetic fields up to 9 T. The cryogenic environment of the STM is generated by a single-shot 3He magnet cryostat in combination with a 4He dewar system. At a base temperature (300 mK), the cryostat has an operation time of approximately 80 h. The special design of the microscope allows the transfer of the STM head from the cryostat to a UHV chamber system, where samples and STM tips can be easily exchanged. The UHV chambers are equipped with specific surface science treatment tools for the functionalization of samples and tips, including high-temperature treatments and thin film deposition. This, in particular, enables spin-resolved tunneling measurements. We present test measurements using well-known samples and tips based on superconductors and metallic materials such as LiFeAs, Nb, Fe, and W. The measurements demonstrate the outstanding performance of the STM with high spatial and energy resolution as well as the spin-resolved capability.

High-power all-fiber ultra-low noise laser

NASA Astrophysics Data System (ADS)

Zhao, Jian; Guiraud, Germain; Pierre, Christophe; Floissat, Florian; Casanova, Alexis; Hreibi, Ali; Chaibi, Walid; Traynor, Nicholas; Boullet, Johan; Santarelli, Giorgio

2018-06-01

High-power ultra-low noise single-mode single-frequency lasers are in great demand for interferometric metrology. Robust, compact all-fiber lasers represent one of the most promising technologies to replace the current laser sources in use based on injection-locked ring resonators or multi-stage solid-state amplifiers. Here, a linearly polarized high-power ultra-low noise all-fiber laser is demonstrated at a power level of 100 W. Special care has been taken in the study of relative intensity noise (RIN) and its reduction. Using an optimized servo actuator to directly control the driving current of the pump laser diode, we obtain a large feedback bandwidth of up to 1.3 MHz. The RIN reaches - 160 dBc/Hz between 3 and 20 kHz.

Structural elucidation of the interaction between neurodegenerative disease-related tau protein with model lipid membranes

NASA Astrophysics Data System (ADS)

Jones, Emmalee M.

A protein's sequence of amino acids determines how it folds. That folded structure is linked to protein function, and misfolding to dysfunction. Protein misfolding and aggregation into beta-sheet rich fibrillar aggregates is connected with over 20 neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized in part by misfolding, aggregation and deposition of the microtubule associated tau protein into neurofibrillary tangles (NFTs). However, two questions remain: What is tau's fibrillization mechanism, and what is tau's cytotoxicity mechanism? Tau is prone to heterogeneous interactions, including with lipid membranes. Lipids have been found in NFTs, anionic lipid vesicles induced aggregation of the microtubule binding domain of tau, and other protein aggregates induced ion permeability in cells. This evidence prompted our investigation of tau's interaction with model lipid membranes to elucidate the structural perturbations those interactions induced in tau protein and in the membrane. We show that although tau is highly charged and soluble, it is highly surface active and preferentially interacts with anionic membranes. To resolve molecular-scale structural details of tau and model membranes, we utilized X-ray and neutron scattering techniques. X-ray reflectivity indicated tau aggregated at air/water and anionic lipid membrane interfaces and penetrated into membranes. More significantly, membrane interfaces induced tau protein to partially adopt a more compact conformation with density similar to folded protein and ordered structure characteristic of beta-sheet formation. This suggests possible membrane-based mechanisms of tau aggregation. Membrane morphological changes were seen using fluorescence microscopy, and X-ray scattering techniques showed tau completely disrupts anionic membranes, suggesting an aggregate-based cytotoxicity mechanism. Further investigation of protein constructs and a "hyperphosphorylation" disease mimic helped

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis.

PubMed

Kraus, Michael; Rapisarda, Attilio; Lam, Max; Thong, Jamie Y J; Lee, Jimmy; Subramaniam, Mythily; Collinson, Simon L; Chong, Siow Ann; Keefe, Richard S E

2016-12-01

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

Caspase-2 cleavage of tau reversibly impairs memory.

PubMed

Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Metabolic changes over the course of aging in a mouse model of tau deposition

PubMed Central

Joly-Amado, Aurélie; Serraneau, Karisa S.; Brownlow, Milene; Marín de Evsikova, Caralina; Speakman, John R.; Gordon, Marcia N.; Morgan, Dave

2016-01-01

Weight loss and food intake disturbances that often precede cognitive decline and diagnosis have been extensively reported in Alzheimer’s disease patients. Previously, we observed that transgenic mice overexpressing tau seemed to eat more food, yet weigh less than non-transgenic littermates. Thus the present longitudinal study measured the time course of changes in metabolic state over the lifespan of the tau depositing Tg4510 mouse model of tau deposition. Although body weight was comparable to non-transgenic littermates at 2 months of age, Tg4510 mice weighed less at older ages. This was accompanied by the accumulation of tau pathology and by dramatically increased activity in all phases of the 24-hour cycle. Resting metabolic rate was also increased at 7 months of age. At 12 months near the end of the Tg4510 lifespan, there was a wasting phase, with a considerable decrease of resting metabolic rate, although hyperactivity was maintained. These diverse changes in metabolism in a mouse model of tau deposition are discussed in the context of known changes in energy metabolism in Alzheimer’s disease. PMID:27318134

Large aperture and wide field of view space telescope for the detection of ultra high energy cosmic rays and neutrinos

NASA Astrophysics Data System (ADS)

Mazzinghi, Piero; Bratina, Vojko; Gambicorti, Lisa; Simonetti, Francesca; Zuccaro Marchi, Alessandro

2017-11-01

New technologies are proposed for large aperture and wide Field of View (FOV) space telescopes dedicated to detection of Ultra High Energy Cosmic Rays and Neutrinos flux, through observation of fluorescence traces in atmosphere and diffused Cerenkov signals. The presented advanced detection system is a spaceborne LEO telescope, with better performance than ground-based observatories, detecting up to 103 - 104 events/year. Different design approaches are implemented, all with very large FOV and focal surface detectors with sufficient segmentation and time resolution to allow precise reconstructions of the arrival direction. In particular, two Schmidt cameras are suggested as an appropriate solution to match most of the optical and technical requirements: large FOV, low f/#, reduction of stray light, optionally flat focal surface, already proven low-cost construction technologies. Finally, a preliminary proposal of a wideFOV retrofocus catadioptric telescope is explained.

SMALLER FOOTPRINT DRILLING SYSTEM FOR DEEP AND HARD ROCK ENVIRONMENTS; FEASIBILITY OF ULTRA-HIGH SPEED DIAMOND DRILLING

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

Alan Black; Arnis Judzis

2004-10-01

The two phase program addresses long-term developments in deep well and hard rock drilling. TerraTek believes that significant improvements in drilling deep hard rock will be obtained by applying ultra-high (greater than 10,000 rpm) rotational speeds. The work includes a feasibility of concept research effort aimed at development and test results that will ultimately result in the ability to reliably drill ''faster and deeper'' possibly with rigs having a smaller footprint to be more mobile. The principle focus is on demonstration testing of diamond bits rotating at speeds in excess of 10,000 rpm to achieve high rate of penetration rockmore » cutting with substantially lower inputs of energy and loads. The project draws on TerraTek results submitted to NASA's ''Drilling on Mars'' program. The objective of that program was to demonstrate miniaturization of a robust and mobile drilling system that expends small amounts of energy. TerraTek successfully tested ultrahigh speed ({approx}40,000 rpm) small kerf diamond coring. Adaptation to the oilfield will require innovative bit designs for full hole drilling or continuous coring and the eventual development of downhole ultra-high speed drives. For domestic operations involving hard rock and deep oil and gas plays, improvements in penetration rates is an opportunity to reduce well costs and make viable certain field developments. An estimate of North American hard rock drilling costs is in excess of $1,200 MM. Thus potential savings of $200 MM to $600 MM are possible if drilling rates are doubled [assuming bit life is reasonable]. The net result for operators is improved profit margin as well as an improved position on reserves. The significance of the ''ultra-high rotary speed drilling system'' is the ability to drill into rock at very low weights on bit and possibly lower energy levels. The drilling and coring industry today does not practice this technology. The highest rotary speed systems in oil field and mining

SMALLER FOOTPRINT DRILLING SYSTEM FOR DEEP AND HARD ROCK ENVIRONMENTS; FEASIBILITY OF ULTRA-HIGH SPEED DIAMOND DRILLING

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

Alan Black; Arnis Judzis

2004-10-01

The two phase program addresses long-term developments in deep well and hard rock drilling. TerraTek believes that significant improvements in drilling deep hard rock will be obtained by applying ultra-high (greater than 10,000 rpm) rotational speeds. The work includes a feasibility of concept research effort aimed at development and test results that will ultimately result in the ability to reliably drill ''faster and deeper'' possibly with rigs having a smaller footprint to be more mobile. The principle focus is on demonstration testing of diamond bits rotating at speeds in excess of 10,000 rpm to achieve high rate of penetration rockmore » cutting with substantially lower inputs of energy and loads. The project draws on TerraTek results submitted to NASA's ''Drilling on Mars'' program. The objective of that program was to demonstrate miniaturization of a robust and mobile drilling system that expends small amounts of energy. TerraTek successfully tested ultrahigh speed ({approx}40,000 rpm) small kerf diamond coring. Adaptation to the oilfield will require innovative bit designs for full hole drilling or continuous coring and the eventual development of downhole ultra-high speed drives. For domestic operations involving hard rock and deep oil and gas plays, improvements in penetration rates is an opportunity to reduce well costs and make viable certain field developments. An estimate of North American hard rock drilling costs is in excess of $1,200 MM. Thus potential savings of $200 MM to $600 MM are possible if drilling rates are doubled [assuming bit life is reasonable]. The net result for operators is improved profit margin as well as an improved position on reserves. The significance of the ''ultra-high rotary speed drilling system'' is the ability to drill into rock at very low weights on bit and possibly lower energy levels. The drilling and coring industry today does not practice this technology. The highest rotary speed systems in oil field and mining

Influence of the world's most challenging mountain ultra-marathon on energy cost and running mechanics.

PubMed

Vernillo, Gianluca; Savoldelli, Aldo; Zignoli, Andrea; Trabucchi, Pietro; Pellegrini, Barbara; Millet, Grégoire P; Schena, Federico

2014-05-01

To examine the effects of the world's most challenging mountain ultra-marathon (Tor des Géants(®) 2012) on the energy cost of three types of locomotion (cycling, level and uphill running) and running kinematics. Before (pre-) and immediately after (post-) the competition, a group of ten male experienced ultra-marathon runners performed in random order three submaximal 4-min exercise trials: cycling at a power of 1.5 W kg(-1) body mass; level running at 9 km h(-1) and uphill running at 6 km h(-1) at an inclination of +15 % on a motorized treadmill. Two video cameras recorded running mechanics at different sampling rates. Between pre- and post-, the uphill-running energy cost decreased by 13.8 % (P = 0.004); no change was noted in the energy cost of level running or cycling (NS). There was an increase in contact time (+10.3 %, P = 0.019) and duty factor (+8.1 %, P = 0.001) and a decrease in swing time (-6.4 %, P = 0.008) in the uphill-running condition. After this extreme mountain ultra-marathon, the subjects modified only their uphill-running patterns for a more economical step mechanics.

Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing.

PubMed

Morey, Rajendra A; Inan, Seniha; Mitchell, Teresa V; Perkins, Diana O; Lieberman, Jeffrey A; Belger, Aysenil

2005-03-01

Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Cross-sectional case-control design. Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d' (a measure based on the hit rate and the false-alarm rate). The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals.

Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro.

PubMed

Whittington, Robert A; Virág, László; Gratuze, Maud; Petry, Franck R; Noël, Anastasia; Poitras, Isabelle; Truchetti, Geoffrey; Marcouiller, François; Papon, Marie-Amélie; El Khoury, Noura; Wong, Kevin; Bretteville, Alexis; Morin, Françoise; Planel, Emmanuel

2015-08-01

There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have, thus, been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine (Dex), an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to nontransgenic mice, Dex-induced tau hyperphosphorylation persisting up to 6 hours in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor antagonist, blocked Dex-induced tau hyperphosphorylation. Furthermore, Dex dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that Dex: (1) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-adrenergic receptor activation, (2) promotes tau aggregation in a mouse model of tauopathy, and (3) impacts spatial reference memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Simulated Cytoskeletal Collapse via Tau Degradation

PubMed Central

Sendek, Austin; Fuller, Henry R.; Hayre, N. Robert; Singh, Rajiv R. P.; Cox, Daniel L.

2014-01-01

We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimers disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundles falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06–0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse. PMID:25162587

Cooperative Game-Based Energy Efficiency Management over Ultra-Dense Wireless Cellular Networks

PubMed Central

Li, Ming; Chen, Pengpeng; Gao, Shouwan

2016-01-01

Ultra-dense wireless cellular networks have been envisioned as a promising technique for handling the explosive increase of wireless traffic volume. With the extensive deployment of small cells in wireless cellular networks, the network spectral efficiency (SE) is improved with the use of limited frequency. However, the mutual inter-tier and intra-tier interference between or among small cells and macro cells becomes serious. On the other hand, more chances for potential cooperation among different cells are introduced. Energy efficiency (EE) has become one of the most important problems for future wireless networks. This paper proposes a cooperative bargaining game-based method for comprehensive EE management in an ultra-dense wireless cellular network, which highlights the complicated interference influence on energy-saving challenges and the power-coordination process among small cells and macro cells. Especially, a unified EE utility with the consideration of the interference mitigation is proposed to jointly address the SE, the deployment efficiency (DE), and the EE. In particular, closed-form power-coordination solutions for the optimal EE are derived to show the convergence property of the algorithm. Moreover, a simplified algorithm is presented to reduce the complexity of the signaling overhead, which is significant for ultra-dense small cells. Finally, numerical simulations are provided to illustrate the efficiency of the proposed cooperative bargaining game-based and simplified schemes. PMID:27649170

Cooperative Game-Based Energy Efficiency Management over Ultra-Dense Wireless Cellular Networks.

PubMed

Li, Ming; Chen, Pengpeng; Gao, Shouwan

2016-09-13

Ultra-dense wireless cellular networks have been envisioned as a promising technique for handling the explosive increase of wireless traffic volume. With the extensive deployment of small cells in wireless cellular networks, the network spectral efficiency (SE) is improved with the use of limited frequency. However, the mutual inter-tier and intra-tier interference between or among small cells and macro cells becomes serious. On the other hand, more chances for potential cooperation among different cells are introduced. Energy efficiency (EE) has become one of the most important problems for future wireless networks. This paper proposes a cooperative bargaining game-based method for comprehensive EE management in an ultra-dense wireless cellular network, which highlights the complicated interference influence on energy-saving challenges and the power-coordination process among small cells and macro cells. Especially, a unified EE utility with the consideration of the interference mitigation is proposed to jointly address the SE, the deployment efficiency (DE), and the EE. In particular, closed-form power-coordination solutions for the optimal EE are derived to show the convergence property of the algorithm. Moreover, a simplified algorithm is presented to reduce the complexity of the signaling overhead, which is significant for ultra-dense small cells. Finally, numerical simulations are provided to illustrate the efficiency of the proposed cooperative bargaining game-based and simplified schemes.

Neurodegenerative disorder FTDP-17-related tau intron 10 +16C → T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice.

PubMed

Umeda, Tomohiro; Yamashita, Takenari; Kimura, Tetsuya; Ohnishi, Kiyouhisa; Takuma, Hiroshi; Ozeki, Tomoko; Takashima, Akihiko; Tomiyama, Takami; Mori, Hiroshi

2013-07-01

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative disorder caused by mutations in the tau gene. Many mutations identified in FTDP-17 have been shown to affect tau exon 10 splicing in vitro, which presumably causes pathologic imbalances in exon 10(-) [3-repeat (3R)] and exon 10(+) [4-repeat (4R)] tau expression and leads to intracellular inclusions of hyperphosphorylated tau in patient brains. However, no reports have investigated this theory using model mice with a tau intronic mutation. Herein, we generated new transgenic mice harboring the tau intron 10 +16C → T mutation. We prepared a transgene construct containing intronic sequences required for exon 10 splicing in the longest tau isoform cDNA. Although mice bearing the construct without the intronic mutation showed normal developmental changes of the tau isoform from 3R tau to equal amounts of 3R and 4R tau, mice with the mutation showed much higher levels of 4R tau at the adult stage. 4R tau was selectively recovered in insoluble brain fractions in their old age. Furthermore, these mice displayed abnormal tau phosphorylation, synapse loss and dysfunction, memory impairment, glial activation, tangle formation, and neuronal loss in an age-dependent manner. These findings provide the first evidence in a mouse model that a tau intronic mutation-induced imbalance of 3R and 4R tau could be a cause of tauopathy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

75 FR 48319 - Ultra-Deepwater Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... DEPARTMENT OF ENERGY Ultra-Deepwater Advisory Committee AGENCY: Department of Energy, Office of...: Purpose of the Committee: The purpose of the Ultra-Deepwater Advisory Committee is to provide advice on development and implementation of programs related to ultra-deepwater architecture and technology to the...

75 FR 54860 - Ultra Deepwater Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... DEPARTMENT OF ENERGY Ultra Deepwater Advisory Committee AGENCY: Department of Energy, Office of... of an open meeting of the Ultra Deepwater Advisory Committee. The Committee was organized pursuant to.../advisorycommittees/UltraDeepwater.html . Issued in Washington, DC, on September 3, 2010. Carol A. Matthews, Committee...

Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment

DOE PAGES

Chung, Peter J.; Song, Chaeyeon; Deek, Joanna; ...

2016-07-25

Tau, an intrinsically disordered protein confined to neuronal axons, binds to and regulates microtubule dynamics. Although there have been observations of string-like microtubule fascicles in the axon initial segment (AIS) and hexagonal bundles in neurite-like processes in non-neuronal cells overexpressing Tau, cell-free reconstitutions have not replicated either geometry. Here we map out the energy landscape of Tau-mediated, GTP-dependent ‘active’ microtubule bundles at 37°C, as revealed by synchrotron SAXS and TEM. Widely spaced bundles (wall-to-wall distance D w–w≈25–41nm) with hexagonal and string-like symmetry are observed, the latter mimicking bundles found in the AIS. A second energy minimum (D w–w≈16–23nm) is revealedmore » under osmotic pressure. The wide spacing results from a balance between repulsive forces, due to Tau’s projection domain (PD), and a stabilizing sum of transient sub-k BT cationic/anionic charge–charge attractions mediated by weakly penetrating opposing PDs. In the end, we find that this landscape would be significantly affected by charge-altering modifications of Tau associated with neurodegeneration.« less

Ultra Fast, High Rep Rate, High Voltage Spark Gap Pulser

DTIC Science & Technology

1995-07-01

current rise time. The spark gap was designed to have a coaxial geometry reducing its inductance. Provisions were made to pass flowing gas between the...ULTRA FAST, HIGH REP RATE, HIGH VOLTAGE SPARK GAP PULSER Robert A. Pastore Jr., Lawrence E. Kingsley, Kevin Fonda, Erik Lenzing Electrophysics and...Modeling Branch AMSRL-PS-EA Tel.: (908)-532-0271 FAX: (908)-542-3348 U.S. Army Research Laboratory Physical Sciences Directorate Ft. Monmouth

Fast and sensitive analysis of beta blockers by ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry.

PubMed

Tomková, Jana; Ondra, Peter; Kocianová, Eva; Václavík, Jan

2017-07-01

This paper presents a method for the determination of acebutolol, betaxolol, bisoprolol, metoprolol, nebivolol and sotalol in human serum by liquid-liquid extraction and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. After liquid-liquid extraction, beta blockers were separated on a reverse-phase analytical column (Acclaim RS 120; 100 × 2.1 mm, 2.2 μm). The total run time was 6 min for each sample. Linearity, limit of detection, limit of quantification, matrix effects, specificity, precision, accuracy, recovery and sample stability were evaluated. The method was successfully applied to the therapeutic drug monitoring of 108 patients with hypertension. This method was also used for determination of beta blockers in 33 intoxicated patients. Copyright © 2016 John Wiley & Sons, Ltd.

Tau-imaging in neurodegeneration.

PubMed

Bischof, Gérard N; Endepols, Heike; van Eimeren, Thilo; Drzezga, Alexander

2017-11-01

Pathological cerebral aggregations of proteins are suggested to play a crucial role in the development of neurodegenerative disorders. For example, aggregation of the protein ß-amyloid in form of extracellular amyloid-plaques as well as intraneuronal depositions of the protein tau in form of neurofibrillary tangles represent hallmarks of Alzheimer's disease (AD). Recently, novel tracers for in vivo molecular imaging of tau-aggregates in the brain have been introduced, complementing existing tracers for imaging amyloid-plaques. Available data on these novel tracers indicate that the subject of Tau-PET may be of considerable complexity. On the one hand this refers to the various forms of appearance of tau-pathology in different types of neurodegenerative disorders. On the other hand, a number of hurdles regarding validation of these tracers still need to be overcome with regard to comparability and standardization of the different tracers, observed off-target/non-specific binding and quantitative interpretation of the signal. These issues will have to be clarified before systematic clinical application of this exciting new methodological approach may become possible. Potential applications refer to early detection of neurodegeneration, differential diagnosis between tauopathies and non-tauopathies and specific patient selection and follow-up in therapy trials. Copyright © 2017. Published by Elsevier Inc.

Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.

PubMed

Tardivel, Meryem; Bégard, Séverine; Bousset, Luc; Dujardin, Simon; Coens, Audrey; Melki, Ronald; Buée, Luc; Colin, Morvane

2016-11-04

A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

BAKABLE ULTRA-HIGH VACUUM VALVE

DOEpatents

Mark, J.T.; Gantz, I.H.

1962-07-10

S>This patent relates to a valve useful in applications involving successively closing and opening a communication between a chamber evacuated to an ultra-high vacuum condition of the order of 10/sup -10/ millimeters of mercury and another chamber or the ambient. The valve is capable of withstanding extended baking at 450 deg C and repeated opening and closing without repiacement of the valve seat (approximately 200 cycle limit). The seal is formed by mutual interdiffusion weld, coerced by a pneumatic actuator. (AEC)

Spacewalking_in_Ultra_High_Definition

NASA Image and Video Library

2017-07-21

Ever wonder what the spacewalker sees while you’re looking at him or her? Here’s your answer, courtesy of NASA astronaut Jack Fischer. This Ultra High Definition clip shows Fischer outside the International Space Station during a spacewalk on Expedition 51 in May 2017, and the view from a small camera attached to his spacesuit at the same time. Music by Joakim Karud. _______________________________________ FOLLOW THE SPACE STATION! Twitter: https://twitter.com/Space_Station Facebook: https://www.facebook.com/ISS Instagram: https://instagram.com/iss/

Review: Tau in biofluids - relation to pathology, imaging and clinical features.

PubMed

Zetterberg, H

2017-04-01

Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Furthermore, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm. Neuroaxonal degeneration and tangle formation are reflected by increased concentrations of total tau (T-tau, measured using assays that detect most forms of tau) and phospho-tau (P-tau, measured using assays with antibodies specific to phosphorylated forms of tau). In AD CSF, both T-tau and P-tau concentrations are increased. In stroke and other CNS disorders with neuroaxonal injury but without tangles, T-tau is selectively increased, whereas P-tau concentration often stays normal. In tauopathies (diseases with both neurodegeneration and neurofibrillary tangles) other than AD, CSF T-tau and P-tau concentrations are typically unaltered, which is a puzzling result that warrants further investigation. In the current review, I discuss the association of T-tau and P-tau concentrations in body fluids with neuropathological changes, imaging findings and clinical features in AD and other CNS diseases. © 2017 British Neuropathological Society.

Ultra-Sensitive Transition-Edge Sensors for the Background Limited Infrared/Sub-mm Spectrograph (BLISS)

NASA Technical Reports Server (NTRS)

Beyer, A. D.; Kenyon, M. E.; Echternach, P. M.; Chui, T.; Eom, B.-H.; Day, P. K.; Bock, J. J.; Holmes, W.A.; Bradford, C. M.

2011-01-01

We report progress in fabricating ultra-sensitive superconducting transition-edge sensors (TESs) for BLISS. BLISS is a suite of grating spectrometers covering 35-433 micron with R approx. 700 cooled to 50 mK that is proposed to fly on the Japanese space telescope SPICA. The detector arrays for BLISS are TES bolometers readout with a time domain SQUID multiplexer. The required noise equivalent power (NEP) for BLISS is NEP = 10(exp -19) W/Hz(exp 1/2) with an ultimate goal of NEP= 5 x 10(exp -20) W/Hz(exp 1/2) to achieve background limited noise performance. The required and goal response times are tau = 150 ms and tau = 50ms respectively to achieve the NEP at the required and goal optical chop frequency 1-5 Hz. We measured prototype BLISS arrays and have achieved NEP = 6 x 10(exp -18) W/Hz(exp 1/2) and tau = 1.4 ms with a Ti TES (T(sub C) = 565 mK) and NEP approx. 2.5 x 10(exp -19) W/Hz(exp 1/2) and tau approximates 4.5 ms with an Ir TES (T(sub C) = 130 mK). Dark power for these tests is estimated at 1-5 fW.

Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study.

PubMed

Lace, G; Savva, G M; Forster, G; de Silva, R; Brayne, C; Matthews, F E; Barclay, J J; Dakin, L; Ince, P G; Wharton, S B

2009-05-01

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

PubMed

Verwilst, Peter; Kim, Hye-Ri; Seo, Jinho; Sohn, Nak-Won; Cha, Seung-Yun; Kim, Yeongmin; Maeng, Sungho; Shin, Jung-Won; Kwak, Jong Hwan; Kang, Chulhun; Kim, Jong Seung

2017-09-27

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 ( 306 VQIVYK 311 ) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aβ-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aβ plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

Bright and ultra-fast scintillation from a semiconductor?

PubMed Central

Derenzo, Stephen E.; Bourret-Courshesne, Edith; Bizarri, Gregory; Canning, Andrew

2015-01-01

Semiconductor scintillators are worth studying because they include both the highest luminosities and shortest decay times of all known scintillators. Moreover, many semiconductors have the heaviest stable elements (Tl, Hg, Pb, Bi) as a major constituent and a high ion pair yield that is proportional to the energy deposited. We review the scintillation properties of semiconductors activated by native defects, isoelectronic impurities, donors and acceptors with special emphasis on those that have exceptionally high luminosities (e.g. ZnO:Zn, ZnS:Ag,Cl, CdS:Ag,Cl) and those that have ultra-fast decay times (e.g. ZnO:Ga; CdS:In). We discuss underlying mechanisms that are consistent with these properties and the possibilities for achieving (1) 200,000 photons/MeV and 1% fwhm energy resolution for 662 keV gamma rays, (2) ultra-fast (ns) decay times and coincident resolving times of 30 ps fwhm for time-of-flight positron emission tomography, and (3) both a high luminosity and an ultra-fast decay time from the same scintillator at cryogenic temperatures. PMID:26855462

Evaluation of chromatic cues for trapping Bactrocera tau.

PubMed

Li, Lei; Ma, Huabo; Niu, Liming; Han, Dongyin; Zhang, Fangping; Chen, Junyu; Fu, Yueguan

2017-01-01

Trapping technology based on chromatic cues is an important strategy in controlling Tephritidae (fruit flies). The objectives of this present study were to evaluate the preference of Bactrocera tau for different chromatic cues, and to explore an easy method to print and reproduce coloured paper. Chromatic cues significantly affected the preference of adult B. tau. Wavelengths in the 515-604 nm range were the suitable wavelengths for trapping B. tau. Different-day-old B. tau had different colour preferences. Virtual wavelengths of 595 nm (yellow) and 568 nm (yellowish green) were the optimum wavelengths for trapping 5-7-day-old B. tau and 30-32-day-old B. tau respectively. The trap type and height significantly influenced B. tau attraction efficiency. The number of B. tau on coloured traps hung perpendicular to plant rows was not significantly higher than the number on traps hung parallel to plant rows. The quantisation of colour on the basis of Bruton's wavelength to RGB function can serve as an alternative method for printing and reproducing coloured paper, but a corrected equation should be established between the theoretical wavelength and actual wavelength of coloured paper. Results show that a compound paper coloured yellow (595 nm) and yellowish green (568 nm) installed at 60 and 90 cm above the ground shows the maximum effect for trapping B. tau. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Methylglyoxal induces tau hyperphosphorylation via promoting AGEs formation.

PubMed

Li, Xiao-Hong; Xie, Jia-Zhao; Jiang, Xia; Lv, Bing-Ling; Cheng, Xiang-Shu; Du, Lai-Ling; Zhang, Jia-Yu; Wang, Jian-Zhi; Zhou, Xin-Wen

2012-12-01

The hyperphosphorylated tau is a major protein component of neurofibrillary tangle, which is one of hallmarks of Alzheimer's disease (AD). While the level of methylglyoxal (MG) is significantly increased in the AD brains, the role of MG in tau phosphorylation is still not reported. Here, we found that MG could induce tau hyperphosphorylation at multiple AD-related sites in neuroblastoma 2a cells under maintaining normal cell viability. MG treatment increased the level of advanced glycation end products (AGEs) and the receptor of AGEs (RAGE). Glycogen synthesis kinase-3β (GSK-3β) and p38 MAPK were activated, whereas the level and activity of JNK, Erk1/2, cdk5, and PP2A were not altered after MG treatment. Simultaneous inhibition of GSK-3β or p38 attenuated the MG-induced tau hyperphosphorylation. Aminoguanidine, a blocker of AGEs formation, could effectively reverse the MG-induced tau hyperphosphorylation. These data suggest that MG induces AD-like tau hyperphosphorylation through AGEs formation involving RAGE up-regulation and GSK-3β activation and p38 activation is also partially involved in MG-induced tau hyperphosphorylation. Thus, targeting MG may be a promising therapeutic strategy to prevent AD-like tau hyperphosphorylation.

Proteopathic tau seeding predicts tauopathy in vivo

PubMed Central

Holmes, Brandon B.; Furman, Jennifer L.; Mahan, Thomas E.; Yamasaki, Tritia R.; Mirbaha, Hilda; Eades, William C.; Belaygorod, Larisa; Cairns, Nigel J.; Holtzman, David M.; Diamond, Marc I.

2014-01-01

Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer’s disease, this model predicts that tau seeds propagate pathology through the brain via cell–cell transfer in neural networks. The critical role of tau seeding activity is untested, however. It is unknown whether seeding anticipates and correlates with subsequent development of pathology as predicted for a causal agent. One major limitation has been the lack of a robust assay to measure proteopathic seeding activity in biological specimens. We engineered an ultrasensitive, specific, and facile FRET-based flow cytometry biosensor assay based on expression of tau or synuclein fusions to CFP and YFP, and confirmed its sensitivity and specificity to tau (∼300 fM) and synuclein (∼300 pM) fibrils. This assay readily discriminates Alzheimer’s disease vs. Huntington's disease and aged control brains. We then carried out a detailed time-course study in P301S tauopathy mice, comparing seeding activity versus histological markers of tau pathology, including MC1, AT8, PG5, and Thioflavin S. We detected robust seeding activity at 1.5 mo, >1 mo before the earliest histopathological stain. Proteopathic tau seeding is thus an early and robust marker of tauopathy, suggesting a proximal role for tau seeds in neurodegeneration. PMID:25261551

Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

PubMed

Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

2015-05-26

Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers

PubMed Central

Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

2016-01-01

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID:27251042

Simulation of ultra-high energy photon propagation with PRESHOWER 2.0

NASA Astrophysics Data System (ADS)

Homola, P.; Engel, R.; Pysz, A.; Wilczyński, H.

2013-05-01

In this paper we describe a new release of the PRESHOWER program, a tool for Monte Carlo simulation of propagation of ultra-high energy photons in the magnetic field of the Earth. The PRESHOWER program is designed to calculate magnetic pair production and bremsstrahlung and should be used together with other programs to simulate extensive air showers induced by photons. The main new features of the PRESHOWER code include a much faster algorithm applied in the procedures of simulating the processes of gamma conversion and bremsstrahlung, update of the geomagnetic field model, and a minor correction. The new simulation procedure increases the flexibility of the code so that it can also be applied to other magnetic field configurations such as, for example, encountered in the vicinity of the sun or neutron stars. Program summaryProgram title: PRESHOWER 2.0 Catalog identifier: ADWG_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADWG_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 3968 No. of bytes in distributed program, including test data, etc.: 37198 Distribution format: tar.gz Programming language: C, FORTRAN 77. Computer: Intel-Pentium based PC. Operating system: Linux or Unix. RAM:< 100 kB Classification: 1.1. Does the new version supercede the previous version?: Yes Catalog identifier of previous version: ADWG_v1_0 Journal reference of previous version: Comput. Phys. Comm. 173 (2005) 71 Nature of problem: Simulation of a cascade of particles initiated by UHE photon in magnetic field. Solution method: The primary photon is tracked until its conversion into an e+ e- pair. If conversion occurs each individual particle in the resultant preshower is checked for either bremsstrahlung radiation (electrons) or secondary gamma conversion (photons). Reasons for

Simulation of ultra-high energy photon propagation in the geomagnetic field

NASA Astrophysics Data System (ADS)

Homola, P.; Góra, D.; Heck, D.; Klages, H.; PeĶala, J.; Risse, M.; Wilczyńska, B.; Wilczyński, H.

2005-12-01

The identification of primary photons or specifying stringent limits on the photon flux is of major importance for understanding the origin of ultra-high energy (UHE) cosmic rays. UHE photons can initiate particle cascades in the geomagnetic field, which leads to significant changes in the subsequent atmospheric shower development. We present a Monte Carlo program allowing detailed studies of conversion and cascading of UHE photons in the geomagnetic field. The program named PRESHOWER can be used both as an independent tool or together with a shower simulation code. With the stand-alone version of the code it is possible to investigate various properties of the particle cascade induced by UHE photons interacting in the Earth's magnetic field before entering the Earth's atmosphere. Combining this program with an extensive air shower simulation code such as CORSIKA offers the possibility of investigating signatures of photon-initiated showers. In particular, features can be studied that help to discern such showers from the ones induced by hadrons. As an illustration, calculations for the conditions of the southern part of the Pierre Auger Observatory are presented. Catalogue identifier:ADWG Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADWG Program obtainable: CPC Program Library, Quen's University of Belfast, N. Ireland Computer on which the program has been thoroughly tested:Intel-Pentium based PC Operating system:Linux, DEC-Unix Programming language used:C, FORTRAN 77 Memory required to execute with typical data:<100 kB No. of bits in a word:32 Has the code been vectorized?:no Number of lines in distributed program, including test data, etc.:2567 Number of bytes in distributed program, including test data, etc.:25 690 Distribution format:tar.gz Other procedures used in PRESHOWER:IGRF [N.A. Tsyganenko, National Space Science Data Center, NASA GSFC, Greenbelt, MD 20771, USA, http://nssdc.gsfc.nasa.gov/space/model/magnetos/data-based/geopack.html], bessik

Ultra-high vacuum compatible induction-heated rod casting furnace

NASA Astrophysics Data System (ADS)

Bauer, A.; Neubauer, A.; Münzer, W.; Regnat, A.; Benka, G.; Meven, M.; Pedersen, B.; Pfleiderer, C.

2016-06-01

We report the design of a radio-frequency induction-heated rod casting furnace that permits the preparation of polycrystalline ingots of intermetallic compounds under ultra-high vacuum compatible conditions. The central part of the system is a bespoke water-cooled Hukin crucible supporting a casting mold. Depending on the choice of the mold, typical rods have a diameter between 6 mm and 10 mm and a length up to 90 mm, suitable for single-crystal growth by means of float-zoning. The setup is all-metal sealed and may be baked out. We find that the resulting ultra-high vacuum represents an important precondition for processing compounds with high vapor pressures under a high-purity argon atmosphere up to 3 bars. Using the rod casting furnace, we succeeded to prepare large high-quality single crystals of two half-Heusler compounds, namely, the itinerant antiferromagnet CuMnSb and the half-metallic ferromagnet NiMnSb.

Ultra-high vacuum compatible induction-heated rod casting furnace.

PubMed

Bauer, A; Neubauer, A; Münzer, W; Regnat, A; Benka, G; Meven, M; Pedersen, B; Pfleiderer, C

2016-06-01

We report the design of a radio-frequency induction-heated rod casting furnace that permits the preparation of polycrystalline ingots of intermetallic compounds under ultra-high vacuum compatible conditions. The central part of the system is a bespoke water-cooled Hukin crucible supporting a casting mold. Depending on the choice of the mold, typical rods have a diameter between 6 mm and 10 mm and a length up to 90 mm, suitable for single-crystal growth by means of float-zoning. The setup is all-metal sealed and may be baked out. We find that the resulting ultra-high vacuum represents an important precondition for processing compounds with high vapor pressures under a high-purity argon atmosphere up to 3 bars. Using the rod casting furnace, we succeeded to prepare large high-quality single crystals of two half-Heusler compounds, namely, the itinerant antiferromagnet CuMnSb and the half-metallic ferromagnet NiMnSb.

Aminothienopyridazines and Methylene Blue Affect Tau Fibrillization via Cysteine Oxidation*

PubMed Central

Crowe, Alex; James, Michael J.; Lee, Virginia M.-Y.; Smith, Amos B.; Trojanowski, John Q.; Ballatore, Carlo; Brunden, Kurt R.

2013-01-01

Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents. PMID:23443659

Consumption of ultra-processed foods predicts diet quality in Canada.

PubMed

Moubarac, Jean-Claude; Batal, M; Louzada, M L; Martinez Steele, E; Monteiro, C A

2017-01-01

This study describes food consumption patterns in Canada according to the types of food processing using the Nova classification and investigates the association between consumption of ultra-processed foods and the nutrient profile of the diet. Dietary intakes of 33,694 individuals from the 2004 Canadian Community Health Survey aged 2 years and above were analyzed. Food and drinks were classified using Nova into unprocessed or minimally processed foods, processed culinary ingredients, processed foods and ultra-processed foods. Average consumption (total daily energy intake) and relative consumption (% of total energy intake) provided by each of the food groups were calculated. Consumption of ultra-processed foods according to sex, age, education, residential location and relative family revenue was assessed. Mean nutrient content of ultra-processed foods and non-ultra-processed foods were compared, and the average nutrient content of the overall diet across quintiles of dietary share of ultra-processed foods was measured. In 2004, 48% of calories consumed by Canadians came from ultra-processed foods. Consumption of such foods was high amongst all socioeconomic groups, and particularly in children and adolescents. As a group, ultra-processed foods were grossly nutritionally inferior to non-ultra-processed foods. After adjusting for covariates, a significant and positive relationship was found between the dietary share of ultra-processed foods and the content in carbohydrates, free sugars, total and saturated fats and energy density, while an inverse relationship was observed with the dietary content in protein, fiber, vitamins A, C, D, B6 and B12, niacin, thiamine, riboflavin, as well as zinc, iron, magnesium, calcium, phosphorus and potassium. Lowering the dietary share of ultra-processed foods and raising consumption of hand-made meals from unprocessed or minimally processed foods would substantially improve the diet quality of Canadian. Copyright © 2016

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

PubMed

Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

2016-07-01

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antici'c, T.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Bäcker, T.; Badescu, A. M.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Beatty, J. J.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Bohácová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Caballero-Mora, K. S.; Caccianiga, B.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; del Río, M.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Fajardo Tapia, I.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Filevich, A.; Filipcic, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Gascon, A.; Gemmeke, H.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, D.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gouffon, P.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Guzman, A.; Hague, J. D.; Hansen, P.; Harari, D.; Harmsma, S.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Horvath, P.; Hrabovský, M.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuehn, F.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; Lauer, R.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Mi'canovi'c, S.; Micheletti, M. I.; Minaya, I. A.; Miramonti, L.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Nyklicek, M.; Oehlschläger, J.; Olinto, A.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Pekala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Sima, O.; 'Smiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanic, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tavera Ruiz, C. G.; Tcaciuc, R.; Tegolo, D.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Toma, G.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberic, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

2012-04-01

Observations of cosmic ray arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Véron-Cetty Véron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energy resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three methods can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. Using data taken from January 1, 2004 to July 31, 2010 we examined the 20,30,...,110 highest energy events with a corresponding minimum energy threshold of about 49.3 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.

Tau Phosphorylation by GSK3 in Different Conditions

PubMed Central

Avila, Jesús; León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; DeFelipe, Javier

2012-01-01

Almost a 20% of the residues of tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on the consequences for tau of being a phosphoprotein. We will focus on serine/threonine phosphorylation. It will be discussed that, depending on the modified residue in tau molecule, phosphorylation could be protective, in processes like hibernation, or toxic like in development of those diseases known as tauopathies, which are characterized by an hyperphosphorylation and aggregation of tau. PMID:22675648

Anti-amyloid beta to tau - based immunization: Developments in immunotherapy for Alzheimer disease.

PubMed

Lambracht-Washington, Doris; Rosenberg, Roger N

2013-08-01

Immunotherapy might provide an effective treatment for Alzheimer disease (AD). A unique feature of AD immunotherapies is that an immune response against a self antigen needs to be elicited without causing adverse autoimmune reactions. Current research is focussed on two possible targets in this regard: One is the inhibition of accumulation and deposition of Amyloid beta 1-42 (Aβ42), which is one of the major peptides found in senile plaques and the second target is hyperphosphorylated tau, which forms neurofibrillary tangles inside the nerve cell and shows association with the progression of dementia. Mouse models have shown that immunotherapy targeting Aβ42 as well as tau with the respective anti-Aβ or anti-tau antibodies can provide significant improvements in these mice. While anti-Aβ immunotherapy (active and passive immunizations) is already in several stages of clinical trials, tau based immunizations have been analyzed only in mouse models. Recently, as a significant correlation of progression of dementia and levels of phoshorylated tau was found, high interest has again focussed on further development of tau based therapies. While Aβ immunotherapy might delay the onset of AD, immunotherapy targeting tau might provide benefits in later stages of this disease. And last but not least, targeting Aβ and tau simultaneously with immunotherapy might provide additional therapeutic effects as these two pathologies are likely synergistic; an approach which has not been tested yet. In this review, we will summarize animal models used to test possible therapies for AD, some of the facts about Aβ42 and tau biology, present on overview on halted, ongoing and upcoming clinical trials together with ongoing preclinical studies targeting tau or Aβ42.

Structured block copolymer thin film composites for ultra-high energy density capacitors

NASA Astrophysics Data System (ADS)

Samant, Saumil; Hailu, Shimelis; Grabowski, Christopher; Durstock, Michael; Raghavan, Dharmaraj; Karim, Alamgir

2014-03-01

Development of high energy density capacitors is essential for future applications like hybrid vehicles and directed energy weaponry. Fundamentally, energy density is governed by product of dielectric permittivity ɛ and breakdown strength Vbd. Hence, improvements in energy density are greatly reliant on improving either ɛ or Vbd or a combination of both. Polymer films are widely used in capacitors due to high Vbd and low loss but they suffer from very low permittivities. Composite dielectrics offer a unique opportunity to combine the high ɛ of inorganic fillers with the high Vbd of a polymer matrix. For enhancement of dielectric properties, it is essential to improve matrix-filler interaction and control the spatial distribution of fillers for which nanostructured block copolymers BCP act as ideal templates. We use Directed Self-assembly of block copolymers to rapidly fabricate highly aligned BCP-TiO2 composite nanostructures in thin films under dynamic thermal gradient field to synergistically combine the high ɛ of functionalized TiO2 and high Vbd of BCP matrix. The results of impact of BCP morphology, processing conditions and concentration of TiO2 on capacitor performance will be reported. U.S. Air Force of Scientific Research under contract FA9550-12-1-0306

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.

PubMed

Bondulich, Marie K; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy; Hanger, Diane P

2016-08-01

Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. © The Author (2016). Published by

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

PubMed Central

Bondulich, Marie K.; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C.; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy

2016-01-01

Abstract Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. PMID:27297240

Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies.

PubMed

Alonso, Alejandra del C; Li, Ben; Grundke-Iqbal, Inge; Iqbal, Khalid

2008-08-01

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's function in microtubule assembly and stabilization and with regards to tau's interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.

Laser beam welding of new ultra-high strength and supra-ductile steels

NASA Astrophysics Data System (ADS)

Dahmen, Martin

2015-03-01

Ultra-high strength and supra-ductile are entering fields of new applications. Those materials are excellent candidates for modern light-weight construction and functional integration. As ultra-high strength steels the stainless martensitic grade 1.4034 and the bainitic steel UNS 53835 are investigated. For the supra-ductile steels stand two high austenitic steels with 18 and 28 % manganese. As there are no processing windows an approach from the metallurgical base on is required. Adjusting the weld microstructure the Q+P and the QT steels require weld heat treatment. The HSD steel is weldable without. Due to their applications the ultra-high strength steels are welded in as-rolled and strengthened condition. Also the reaction of the weld on hot stamping is reflected for the martensitic grades. The supra-ductile steels are welded as solution annealed and work hardened by 50%. The results show the general suitability for laser beam welding.

A Silicon Disk with Sandwiched Piezoelectric Springs for Ultra-low Frequency Energy Harvesting

NASA Astrophysics Data System (ADS)

Lu, J.; Zhang, L.; Yamashita, T.; Takei, R.; Makimoto, N.; Kobayashi, T.

2015-12-01

Exploiting the sporadic availability of energy by energy harvesting devices is an attractive solution to power wireless sensor nodes and many other distributed modules for much longer operation duration and much lower maintenance cost after they are deployed. MEMS energy harvesting devices exhibit unique advantageous of super-compact size, mass productivity, and easy-integration with sensors, actuators and other integrated circuits. However, MEMS vibration energy harvesting devices are rather difficult to be used practically due to their poor response to most of the ambient vibrations at ultra-low frequency range. In this paper, a micromachined silicon disk with sandwiched piezoelectric springs was successfully developed with resonant frequency of 15.36∼42.42 Hz and quality factor of 39∼55 for energy harvesting. Footprint size of the device was 6 mm × 6 mm, which is less than half of the piezoelectric cantilevers, while the device can scavenge reasonably high power of 0.57 μW at the acceleration of 0.1 g. The evaluation results also suggested that the device was quite sensitive as a sensor for selective monitoring of vibrations at a certain frequency.

Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration

PubMed Central

Hoover, Brian R.; Reed, Miranda N.; Su, Jianjun; Penrod, Rachel D.; Kotilinek, Linda A.; Grant, Marianne K.; Pitstick, Rose; Carlson, George A.; Lanier, Lorene M.; Yuan, Li-Lian; Ashe, Karen H.; Liao, Dezhi

2010-01-01

The microtubule-associated protein tau accumulates in Alzheimer’s and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of synapses or neurons, but rather as a result of synaptic abnormalities caused by the accumulation of hyperphosphorylated tau within intact dendritic spines, where it disrupts synaptic function by impairing glutamate receptor trafficking or synaptic anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid residues to create pseudohyperphosphorylated tau caused tau mislocalization while creation of phosphorylation-deficient tau blocked the mis-targeting of tau to dendritic spines. Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines. PMID:21172610

Manganese oxide micro-supercapacitors with ultra-high areal capacitance

NASA Astrophysics Data System (ADS)

Wang, Xu; Myers, Benjamin D.; Yan, Jian; Shekhawat, Gajendra; Dravid, Vinayak; Lee, Pooi See

2013-05-01

A symmetric micro-supercapacitor is constructed by electrochemically depositing manganese oxide onto micro-patterned current collectors. High surface-to-volume ratio of manganese oxide and short diffusion distance between electrodes give an ultra-high areal capacitance of 56.3 mF cm-2 at a current density of 27.2 μA cm-2.A symmetric micro-supercapacitor is constructed by electrochemically depositing manganese oxide onto micro-patterned current collectors. High surface-to-volume ratio of manganese oxide and short diffusion distance between electrodes give an ultra-high areal capacitance of 56.3 mF cm-2 at a current density of 27.2 μA cm-2. Electronic supplementary information (ESI) available: Experimental procedures; optical images of micro-supercapacitors; areal capacitances of samples M-0.3C, M-0.6C and M-0.9C; illustration of interdigital finger electrodes; Nyquist plot of Co(OH)2 deposited on micro-electrodes. See DOI: 10.1039/c3nr00210a

Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus

PubMed Central

Chalermpalanupap, Termpanit; Weinshenker, David

2017-01-01

Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer's disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression. PMID:29038736

Ultra-high power capabilities in amorphous FePO4 thin films

NASA Astrophysics Data System (ADS)

Gandrud, Knut B.; Nilsen, Ola; Fjellvåg, Helmer

2016-02-01

Record breaking electrochemical properties of FePO4 have been found through investigation of the thickness dependent electrochemical properties of amorphous thin film electrodes. Atomic layer deposition was used for production of thin films of amorphous FePO4 with highly accurate thickness and topography. Electrochemical characterization of these thin film electrodes revealed that the thinner electrodes behave in a pseudocapacitive manner even at high rates of Li+ de/intercalation, which enabled specific powers above 1 MW kg-1 FePO4 to be obtained with minimal capacity loss. In addition, a self-enhancing kinetic effect was observed during cycling enabling more than 10,000 cycles at current rates approaching that of a supercapacitor (11s charge/discharge). The current findings may open for construction of ultra-high power battery electrodes that combines the energy density of batteries with the power capabilities of supercapacitors.

Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons.

PubMed

Patil, Sachin; Chan, Christina

2005-08-26

Epidemiological studies suggest that high fat diets significantly increase the risk of Alzheimer's disease (AD). In addition, the AD brain is characterized by high fatty acid content compared to that of healthy subjects. Nevertheless, the basic mechanism relating elevated fatty acids and the pathogenesis of AD remains unclear. The present study examines the role of fatty acids in causing hyperphosphorylation of the tau protein, one of the characteristic signatures of AD pathology. Hyperphosphorylation of tau disrupts the cell cytoskeleton and leads to neuronal degeneration. Here, primary rat cortical neurons and astrocytes were treated with saturated free fatty acids (FFAs), palmitic and stearic acids. There was no change in the levels of phosphorylated tau in rat cortical neurons treated directly with these FFAs. The conditioned media from FFA-treated astrocytes, however, caused hyperphosphorylation of tau in the cortical neurons at AD-specific phospho-epitopes. Co-treatment of neurons with N-acetyl cysteine, an antioxidant, reduced FFA-induced hyperphosphorylation of tau. The present results establish a central role of FFAs in causing hyperphosphorylation of tau through astroglia-mediated oxidative stress.

Further demonstration of the VRLA-type UltraBattery under medium-HEV duty and development of the flooded-type UltraBattery for micro-HEV applications

NASA Astrophysics Data System (ADS)

Furukawa, J.; Takada, T.; Monma, D.; Lam, L. T.

The UltraBattery has been invented by the CSIRO Energy Technology in Australia and has been developed and produced by the Furukawa Battery Co., Ltd., Japan. This battery is a hybrid energy storage device which combines a super capacitor and a lead-acid battery in single unit cells, taking the best from both technologies without the need of extra, expensive electronic controls. The capacitor enhances the power and lifespan of the lead-acid battery as it acts as a buffer during high-rate discharging and charging, thus enabling it to provide and absorb charge rapidly during vehicle acceleration and braking. The laboratory results of the prototype valve-regulated UltraBatteries show that the capacity, power, available energy, cold cranking and self-discharge of these batteries have met, or exceeded, all the respective performance targets set for both minimum and maximum power-assist HEVs. The cycling performance of the UltraBatteries under micro-, mild- and full-HEV duties is at least four times longer than that of the state-of-the-art lead-acid batteries. Importantly, the cycling performance of UltraBatteries is proven to be comparable or even better than that of the Ni-MH cells. On the other hand, the field trial of UltraBatteries in the Honda Insight HEV shows that the vehicle has surpassed 170,000 km and the batteries are still in a healthy condition. Furthermore, the UltraBatteries demonstrate very good acceptance of the charge from regenerative braking even at high state-of-charge, e.g., 70% during driving. Therefore, no equalization charge is required for the UltraBatteries during field trial. The HEV powered by UltraBatteries gives slightly higher fuel consumption (cf., 4.16 with 4.05 L/100 km) and CO 2 emissions (cf., 98.8 with 96 g km -1) compared with that by Ni-MH cells. There are no differences in driving experience between the Honda Insight powered by UltraBatteries and by Ni-MH cells. Given such comparable performance, the UltraBattery pack costs

The Calibration of an Ultra-High Energy Muon Hodoscope and Search for Cosmic Gamma Ray Anisotropies.

NASA Astrophysics Data System (ADS)

McCarthy, Thomas K.

1996-01-01

The Homestake Deep Underground Hodoscope is a liquid scintillation detector that lies at a depth of 4200 mwe within a cavernous chamber of granite within the Homestake Gold Mine. At this depth, it is shielded from all but the most energetic elementary particles, in particular, muons with an energy of less than 27 TeV. Consequently, primaries with energies greater than 1 PeV are indirectly detected. The detector has two tiers of detectors each comprised of 40 scintillation modules of dimension.305 m x.305 m x 7.925 m, separated by a distance of 8.047 m. With this geometrical arrangement and the use of fast timing triggers (2.5 ns resolution), a directional study of ultra -high energy particles was conducted. By exploiting the fact that these particles enter the detector at very nearly the speed of light and that the trigger window has a fixed timing limit, a methodology was developed to fine tune the detector using these constraints. Once calibration was established, noisy events are easily eliminated and the resulting data is used to compute the flux of muons entering the detector, to plot the number of muons entering the detector as a function of angle and to compare this with theoretical profiles and, finally, to extrapolate the muon's velocity vector back onto the celestial sphere to search for anisotropies. The results of this study indicate a flux that is constant in time and is consistent with other, independent measurements. The angular profile is consistent with theoretical models, although a different scale factor was required to make a precise agreement. This may be due to the particular nature of the Homestake stratum. There was no indication for discrete gamma ray sources of cosmic origin, supporting earlier work using the same detector. Lastly, the methodology developed can be applied to similar detection facilities that are in operation on a long term basis. With its use of a personal computer, on site, a large facility could be monitored quite

New-type steel plate with ultra high crack-arrestability

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

Ishikawa, T.; Nomiyama, Y.; Hagiwara, Y.

1995-12-31

A new-type steel plate has been developed by controlling the microstructure of the surface layers. The surface layer consists of ultra fine grain ferrite microstructure, which provides excellent fracture toughness even at cryogenic temperature. When an unstable brittle crack propagates in the developed steel plate, shear-lips can be easily formed due to the surface layers with ultra fine grain microstructure. Since unstable running crack behavior is strongly affected by side-ligaments (shear-lips), which are associated with extensive plastic deformation, enhanced formation of the shear-lips can improve crack arrestability. This paper describes the developed steel plates of HT500MPa tensile strength class formore » shipbuilding use. Fracture mechanics investigations using large-scale fracture testings (including ultrawide duplex ESSO tests) clarified that the developed steel plates have ultra high crack-arrestability. It was also confirmed that the plates possess sufficient properties, including weldability and workability, for ship building use.« less

Mutual relationship between Tau and central insulin signalling: consequences for AD and Tauopathies ?

PubMed

Gratuze, Maud; Joly-Amado, Aurélie; Vieau, Didier; Buée, Luc; Blum, David

2018-02-13

Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments and lower brain glucose metabolism, that often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding on the role of insulin in the brain and its relation to Tau protein in the context of AD and Tauopathies. Considering that insulin signaling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in term of cognition.
. ©2018S. Karger AG, Basel.

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

PubMed Central

Reyes, Juan F.; Fu, Yifan; Vana, Laurel; Kanaan, Nicholas M.; Binder, Lester I.

2011-01-01

A substantial body of evidence suggests that nitrative injury contributes to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. Previously, we showed in vitro that within the tau protein the N-terminal tyrosine residues (Y18 and Y29) are more susceptible to nitrative modifications than other tyrosine sites (Y197 and Y394). Using site-specific antibodies to nitrated tau at Y18 and Y29, we identified tau nitrated in both glial (Y18) and neuronal (Y29) tau pathologies. In this study, we report the characterization of two novel monoclonal antibodies, Tau-nY197 and Tau-nY394, recognizing tau nitrated at Y197 and Y394, respectively. By Western blot analysis, Tau-nY197 labeled soluble tau and insoluble paired helical filament proteins (PHF-tau) nitrated at Y197 from control and AD brain samples. Tau-nY394 failed to label soluble tau isolated from control or severe AD samples, but labeled insoluble PHF-tau to a limited extent. Immunohistochemical analysis using Tau-nY197 revealed the hallmark tau pathology associated with AD; Tau-nY394 did not detect any pathological lesions characteristic of the disorder. These data suggest that a subset of the hallmark pathological inclusions of AD contain tau nitrated at Y197. However, nitration at Y197 was also identified in soluble tau from all control samples, including those at Braak stage 0, suggesting that nitration at this site in the proline-rich region of tau may have normal biological functions in the human brain. PMID:21514440

Complete mitochondrial genome of Zeugodacus tau (Insecta: Tephritidae) and differentiation of Z. tau species complex by mitochondrial cytochrome c oxidase subunit I gene

PubMed Central

Yong, Hoi-Sen; Lim, Phaik-Eem; Eamsobhana, Praphathip

2017-01-01

The tephritid fruit fly Zeugodacus tau (Walker) is a polyphagous fruit pest of economic importance in Asia. Studies based on genetic markers indicate that it forms a species complex. We report here (1) the complete mitogenome of Z. tau from Malaysia and comparison with that of China as well as the mitogenome of other congeners, and (2) the relationship of Z. tau taxa from different geographical regions based on sequences of cytochrome c oxidase subunit I gene. The complete mitogenome of Z. tau had a total length of 15631 bp for the Malaysian specimen (ZT3) and 15835 bp for the China specimen (ZT1), with similar gene order comprising 37 genes (13 protein-coding genes—PCGs, 2 rRNA genes, and 22 tRNA genes) and a non-coding A + T-rich control region (D-loop). Based on 13 PCGs and 15 mt-genes, Z. tau NC_027290 (China) and Z. tau ZT1 (China) formed a sister group in the lineage containing also Z. tau ZT3 (Malaysia). Phylogenetic analysis based on partial sequences of cox1 gene indicates that the taxa from China, Japan, Laos, Malaysia, Bangladesh, India, Sri Lanka, and Z. tau sp. A from Thailand belong to Z. tau sensu stricto. A complete cox1 gene (or 13 PCGs or 15 mt-genes) instead of partial sequence is more appropriate for determining phylogenetic relationship. PMID:29216281

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

PubMed

Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

2016-01-01

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

PubMed Central

Ferrer, Isidro; Grinberg, Lea T.; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J.; Crary, John F.; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M.; Ironside, James W.; Love, Seth; Mackenzie, Ian R.; Munoz, David G.; Murray, Melissa E.; Nelson, Peter T.; Takahashi, Hitoshi; Trojanowski, John Q.; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G.; Bieniek, Kevin F.; Bigio, Eileen H.; Bodi, Istvan; Dugger, Brittany N.; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M.; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Heale, Richard; Hof, Patrick R.; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A.; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J.; Mann, David M.; Matej, Radoslav; McKee, Ann C.; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J.; Murayama, Shigeo; Lee, Edward B.; Rahimi, Jasmin; Rodriguez, Roberta D.; Rozemüller, Annemieke; Schneider, Julie A.; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B.; Tolnay, Markus; Troncoso, Juan C.; Vinters, Harry V.; Weis, Serge; Wharton, Stephen B.; White, Charles L.; Wisniewski, Thomas; Woulfe, John M.; Yamada, Masahito

2016-01-01

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

Application of ultra-high performance concrete to bridge girders.

DOT National Transportation Integrated Search

2009-02-01

"Ultra-High Performance Concrete (UHPC) is a new class of concrete that has superior performance characteristics : compared to conventional concrete. The enhanced strength and durability properties of UHPC are mainly due to optimized : particle grada...

A 10 mK scanning tunneling microscope operating in ultra high vacuum and high magnetic fields.

PubMed

Assig, Maximilian; Etzkorn, Markus; Enders, Axel; Stiepany, Wolfgang; Ast, Christian R; Kern, Klaus

2013-03-01

We present design and performance of a scanning tunneling microscope (STM) that operates at temperatures down to 10 mK providing ultimate energy resolution on the atomic scale. The STM is attached to a dilution refrigerator with direct access to an ultra high vacuum chamber allowing in situ sample preparation. High magnetic fields of up to 14 T perpendicular and up to 0.5 T parallel to the sample surface can be applied. Temperature sensors mounted directly at the tip and sample position verified the base temperature within a small error margin. Using a superconducting Al tip and a metallic Cu(111) sample, we determined an effective temperature of 38 ± 1 mK from the thermal broadening observed in the tunneling spectra. This results in an upper limit for the energy resolution of ΔE = 3.5 kBT = 11.4 ± 0.3 μeV. The stability between tip and sample is 4 pm at a temperature of 15 mK as demonstrated by topography measurements on a Cu(111) surface.

The sensitivity of past and near-future lunar radio experiments to ultra-high-energy cosmic rays and neutrinos

NASA Astrophysics Data System (ADS)

Bray, J. D.

2016-04-01

Various experiments have been conducted to search for the radio emission from ultra-high-energy (UHE) particles interacting in the lunar regolith. Although they have not yielded any detections, they have been successful in establishing upper limits on the flux of these particles. I present a review of these experiments in which I re-evaluate their sensitivity to radio pulses, accounting for effects which were neglected in the original reports, and compare them with prospective near-future experiments. In several cases, I find that past experiments were substantially less sensitive than previously believed. I apply existing analytic models to determine the resulting limits on the fluxes of UHE neutrinos and cosmic rays (CRs). In the latter case, I amend the model to accurately reflect the fraction of the primary particle energy which manifests in the resulting particle cascade, resulting in a substantial improvement in the estimated sensitivity to CRs. Although these models are in need of further refinement, in particular to incorporate the effects of small-scale lunar surface roughness, their application here indicates that a proposed experiment with the LOFAR telescope would test predictions of the neutrino flux from exotic-physics models, and an experiment with a phased-array feed on a large single-dish telescope such as the Parkes radio telescope would allow the first detection of CRs with this technique, with an expected rate of one detection per 140 h.

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

Ultra-high-field magnetic resonance spectroscopy in non-alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non-alcoholic steatohepatitis and advanced fibrosis.

PubMed

Traussnigg, Stefan; Kienbacher, Christian; Gajdošík, Martin; Valkovič, Ladislav; Halilbasic, Emina; Stift, Judith; Rechling, Christian; Hofer, Harald; Steindl-Munda, Petra; Ferenci, Peter; Wrba, Fritz; Trattnig, Siegfried; Krššák, Martin; Trauner, Michael

2017-10-01

With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22). Hepatic lipid content and composition were measured using 3-Tesla proton ( 1 H)-MRS. 7-Tesla phosphorus ( 31 P)-MRS was applied to determine phosphomonoester (PME) including phosphoethanolamine (PE), phosphodiester (PDE) including glycerophosphocholine (GPC), phosphocreatine (PCr), nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate (Pi), γ-ATP and total phosphorus (TP). Saturation transfer technique was used to quantify hepatic ATP flux. Hepatic steatosis in 1 H-MRS highly correlated with histology (P<.001) showing higher values in NASH than NAFL (P<.001) without differences in saturated or unsaturated fatty acid indices. PE/TP ratio increased with advanced fibrosis (F3/4) (P=.002) whereas GPC/PME+PDE decreased (P=.05) compared to no/mild fibrosis (F0-2). γ-ATP/TP was lower in advanced fibrosis (P=.049), while PCr/TP increased (P=.01). NADPH/TP increased with higher grades of ballooning (P=.02). Pi-to-ATP exchange rate constant (P=.003) and ATP flux (P=.001) were lower in NASH than NAFL. Ultra-high-field MRS, especially saturation transfer technique uncovers changes in energy metabolism including dynamic ATP flux in inflammation and fibrosis in NASH. Non-invasive profiling by MRS appears feasible and may assist further mechanistic and therapeutic studies in NAFLD/NASH. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

Is a massive tau neutrino just what cold dark matter needs?

NASA Technical Reports Server (NTRS)

Dodelson, Scott; Gyuk, Geza; Turner, Michael S.

1994-01-01

The cold dark matter (CDM) scenario for structure formation in the Universe is very attractive and has many successes; however, when its spectrum of density perturbations is normalized to the COBE anisotropy measurement the level of inhomogeneity predicted on small scales is too large. This can be remedied by a tau neutrino of mass 1 MeV - 10MeV and lifetime 0.1 sec - 100 sec whose decay products include electron neutrinos because it allows the total energy density in relativistic particles to be doubled without interfering with nucleosynthesis. The anisotropies predicted on the degree scale for 'tau CDM' are larger than standard CDM. Experiments at e(sup +/-) collides may be able to probe such a mass range.

Study on creep of fiber reinforced ultra-high strength concrete based on strength

NASA Astrophysics Data System (ADS)

Peng, Wenjun; Wang, Tao

2018-04-01

To complement the creep performance of ultra-high strength concrete, the long creep process of fiber reinforced concrete was studied in this paper. The long-term creep process and regularity of ultra-high strength concrete with 0.5% PVA fiber under the same axial compression were analyzed by using concrete strength (C80/C100/C120) as a variable. The results show that the creep coefficient of ultra-high strength concrete decreases with the increase of concrete strength. Compared with ACI209R (92), GL2000 models, it is found that the predicted value of ACI209R (92) are close to the experimental value, and the creep prediction model suitable for this experiment is proposed based on ACI209R (92).

A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

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

Abreu, P.

2012-01-01

Observations of cosmic ray arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Veron-Cetty Veron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energymore » resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three methods can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. Using data taken from January 1, 2004 to July 31, 2010 we examined the 20, 30, ..., 110 highest energy events with a corresponding minimum energy threshold of about 51 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.« less

Bacterial co-expression of human Tau protein with protein kinase A and 14-3-3 for studies of 14-3-3/phospho-Tau interaction

PubMed Central

Tugaeva, Kristina V.; Tsvetkov, Philipp O.

2017-01-01

Abundant regulatory 14-3-3 proteins have an extremely wide interactome and coordinate multiple cellular events via interaction with specifically phosphorylated partner proteins. Notwithstanding the key role of 14-3-3/phosphotarget interactions in many physiological and pathological processes, they are dramatically underexplored. Here, we focused on the 14-3-3 interaction with human Tau protein associated with the development of several neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Among many known phosphorylation sites within Tau, protein kinase A (PKA) phosphorylates several key residues of Tau and induces its tight interaction with 14-3-3 proteins. However, the stoichiometry and mechanism of 14-3-3 interaction with phosphorylated Tau (pTau) are not clearly elucidated. In this work, we describe a simple bacterial co-expression system aimed to facilitate biochemical and structural studies on the 14-3-3/pTau interaction. We show that dual co-expression of human fetal Tau with PKA in Escherichia coli results in multisite Tau phosphorylation including also naturally occurring sites which were not previously considered in the context of 14-3-3 binding. Tau protein co-expressed with PKA displays tight functional interaction with 14-3-3 isoforms of a different type. Upon triple co-expression with 14-3-3 and PKA, Tau protein could be co-purified with 14-3-3 and demonstrates complex which is similar to that formed in vitro between individual 14-3-3 and pTau obtained from dual co-expression. Although used in this study for the specific case of the previously known 14-3-3/pTau interaction, our co-expression system may be useful to study of other selected 14-3-3/phosphotarget interactions and for validations of 14-3-3 complexes identified by other methods. PMID:28575131

An efficient, movable single-particle detector for use in cryogenic ultra-high vacuum environments.

PubMed

Spruck, Kaija; Becker, Arno; Fellenberger, Florian; Grieser, Manfred; von Hahn, Robert; Klinkhamer, Vincent; Novotný, Oldřich; Schippers, Stefan; Vogel, Stephen; Wolf, Andreas; Krantz, Claude

2015-02-01

A compact, highly efficient single-particle counting detector for ions of keV/u kinetic energy, movable by a long-stroke mechanical translation stage, has been developed at the Max-Planck-Institut für Kernphysik (Max Planck Institute for Nuclear Physics, MPIK). Both, detector and translation mechanics, can operate at ambient temperatures down to ∼10 K and consist fully of ultra-high vacuum compatible, high-temperature bakeable, and non-magnetic materials. The set-up is designed to meet the technical demands of MPIK's Cryogenic Storage Ring. We present a series of functional tests that demonstrate full suitability for this application and characterise the set-up with regard to its particle detection efficiency.

Alzheimer's amyloid-β oligomers rescue cellular prion protein induced tau reduction via the Fyn pathway.

PubMed

Chen, Rong-Jie; Chang, Wei-Wei; Lin, Yu-Chun; Cheng, Pei-Lin; Chen, Yun-Ru

2013-09-18

Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP(C)) where the role of PrP(C) in AD is still not fully understood. To investigate the downstream mechanism of PrP(C) and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP(C) and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP(C) overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP(C), the high AD risk polymorphic allele in human prion gene. PrP(C) lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP(C) effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP(C)-induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ-PrP(C)-tau signaling. Overall, our results demonstrated that PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP(C), tau, and Aβ oligomers.

Tau Kinetics in Neurons and the Human Central Nervous System.

PubMed

Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G; Patterson, Bruce W; Gordon, Brian A; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J; Kasten, Tom; Kirmess, Kristopher M; Kanaan, Nicholas M; Yarasheski, Kevin E; Baker-Nigh, Alaina; Benzinger, Tammie L S; Miller, Timothy M; Karch, Celeste M; Bateman, Randall J

2018-03-21

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Passive Immunization with Anti-Tau Antibodies in Two Transgenic Models

PubMed Central

Chai, Xiyun; Wu, Su; Murray, Tracey K.; Kinley, Robert; Cella, Claire V.; Sims, Helen; Buckner, Nicola; Hanmer, Jenna; Davies, Peter; O'Neill, Michael J.; Hutton, Michael L.; Citron, Martin

2011-01-01

The microtubule-associated protein Tau plays a critical role in the pathogenesis of Alzheimer disease and several related disorders (tauopathies). In the disease Tau aggregates and becomes hyperphosphorylated forming paired helical and straight filaments, which can further condense into higher order neurofibrillary tangles in neurons. The development of this pathology is consistently associated with progressive neuronal loss and cognitive decline. The identification of tractable therapeutic targets in this pathway has been challenging, and consequently very few clinical studies addressing Tau pathology are underway. Recent active immunization studies have raised the possibility of modulating Tau pathology by activating the immune system. Here we report for the first time on passive immunotherapy for Tau in two well established transgenic models of Tau pathogenesis. We show that peripheral administration of two antibodies against pathological Tau forms significantly reduces biochemical Tau pathology in the JNPL3 mouse model. We further demonstrate that peripheral administration of the same antibodies in the more rapidly progressive P301S tauopathy model not only reduces Tau pathology quantitated by biochemical assays and immunohistochemistry, but also significantly delays the onset of motor function decline and weight loss. This is accompanied by a reduction in neurospheroids, providing direct evidence of reduced neurodegeneration. Thus, passive immunotherapy is effective at preventing the buildup of intracellular Tau pathology, neurospheroids, and associated symptoms, although the exact mechanism remains uncertain. Tau immunotherapy should therefore be considered as a therapeutic approach for the treatment of Alzheimer disease and other tauopathies. PMID:21841002

March separate, strike together--role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease.

PubMed

Eckert, Anne; Nisbet, Rebecca; Grimm, Amandine; Götz, Jürgen

2014-08-01

The energy demand and calcium buffering requirements of the brain are met by the high number of mitochondria in neurons and in these, especially at the synapses. Mitochondria are the major producer of reactive oxygen species (ROS); at the same time, they are damaged by ROS that are induced by abnormal protein aggregates that characterize human neurodegenerative diseases such as Alzheimer's disease (AD). Because synaptic mitochondria are long-lived, any damage exerted by these aggregates impacts severely on neuronal function. Here we review how increased TAU, a defining feature of AD and related tauopathies, impairs mitochondrial function by following the principle: 'March separate, strike together!' In the presence of amyloid-β, TAU's toxicity is augmented suggesting synergistic pathomechanisms. In order to restore mitochondrial functions in neurodegeneration as a means of therapeutic intervention it will be important to integrate the various aspects of dysfunction and get a handle on targeting distinct cell types and subcellular compartments. © 2013.

Human Tau Isoforms Assemble into Ribbon-like Fibrils That Display Polymorphic Structure and Stability*

PubMed Central

Wegmann, Susanne; Jung, Yu Jin; Chinnathambi, Subashchandrabose; Mandelkow, Eva-Maria; Mandelkow, Eckhard; Muller, Daniel J.

2010-01-01

Fibrous aggregates of Tau protein are characteristic features of Alzheimer disease. We applied high resolution atomic force and EM microscopy to study fibrils assembled from different human Tau isoforms and domains. All fibrils reveal structural polymorphism; the “thin twisted” and “thin smooth” fibrils resemble flat ribbons (cross-section ∼10 × 15 nm) with diverse twist periodicities. “Thick fibrils” show periodicities of ∼65–70 nm and thicknesses of ∼9–18 nm such as routinely reported for “paired helical filaments” but structurally resemble heavily twisted ribbons. Therefore, thin and thick fibrils assembled from different human Tau isoforms challenge current structural models of paired helical filaments. Furthermore, all Tau fibrils reveal axial subperiodicities of ∼17–19 nm and, upon exposure to mechanical stress or hydrophobic surfaces, disassemble into uniform fragments that remain connected by thin thread-like structures (∼2 nm). This hydrophobically induced disassembly is inhibited at enhanced electrolyte concentrations, indicating that the fragments resemble structural building blocks and the fibril integrity depends largely on hydrophobic and electrostatic interactions. Because full-length Tau and repeat domain constructs assemble into fibrils of similar thickness, the “fuzzy coat” of Tau protein termini surrounding the fibril axis is nearly invisible for atomic force microscopy and EM, presumably because of its high flexibility. PMID:20566652

Field Evaluation of Ultra-High Pressure Water Systems for Runway Rubber Removal

DTIC Science & Technology

2014-04-01

ER D C/ G SL T R- 14 -1 1 Field Evaluation of Ultra-High Pressure Water Systems for Runway Rubber Removal G eo te ch ni ca l a nd S tr...Field Evaluation of Ultra-High Pressure Water Systems for Runway Rubber Removal Aaron B. Pullen Applied Research Associates, Inc. 421 Oak Avenue...collaboration with Applied Research Associates, Inc. (ARA). Several types of commercial UHPW water blasting systems were tested on an ungrooved portland cement

Ultra high vacuum test setup for electron gun

NASA Astrophysics Data System (ADS)

Pandiyar, M. L.; Prasad, M.; Jain, S. K.; Kumar, R.; Hannurkar, P. R.

2008-05-01

Ultra High Vacuum (UHV) test setup for electron gun testing has been developed. The development of next generation light sources and accelerators require development of klystron as a radio frequency power source, and in turn electron gun. This UHV electron gun test setup can be used to test the electron guns ranging from high average current, quasi-continuous wave to high peak current, single pulse etc. An electron gun has been designed, fabricated, assembled and tested for insulation up to 80 kV under the programme to develop high power klystron for future accelerators. Further testing includes the electron emission parameters characterization of the cathode, as it determines the development of a reliable and efficient electron gun with high electron emission current and high life time as well. This needs a clean ultra high vacuum to study these parameters particularly at high emission current. The cathode emission current, work function and vapour pressure of cathode surface material at high temperature studies will further help in design and development of high power electron gun The UHV electron gun test setup consists of Turbo Molecular Pump (TMP), Sputter Ion Pump (SIP), pressure gauge, high voltage and cathode power supplies, current measurement device, solenoid magnet and its power supply, residual gas analyser etc. The ultimate vacuum less than 2×10-9 mbar was achieved. This paper describes the UHV test setup for electron gun testing.

The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.

PubMed

de Leon, Mony J; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; Saint-Louis, Les; Kim, Hee-Jin; Fortea, Juan; Fossati, Silvia; Laska, Eugene; Siegel, Carole; Butler, Tracy; Li, Yi; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj

2018-01-01

Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.

Bond behavior of reinforcing steel in ultra-high performance concrete.

DOT National Transportation Integrated Search

2014-10-01

Ultra-High Performance Concrete (UHPC) is a relatively new class of advanced cementitious composite : materials, which exhibits high compressive [above 21.7 ksi (150 MPa)] and tensile [above 0.72 ksi (5 MPa)] : strengths. The discrete steel fiber rei...

Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease.

PubMed

Tracy, Tara E; Gan, Li

2018-05-09

The accumulation of pathological tau in the brain is associated with neuronal deterioration and cognitive impairments in tauopathies including Alzheimer's disease. Tau, while primarily localized in the axons of healthy neurons, accumulates in the soma and dendrites of neurons under pathogenic conditions. Tau is found in both presynaptic and postsynaptic compartments of neurons in Alzheimer's disease. New research supports that soluble forms of tau trigger pathophysiology in the brain by altering properties of synaptic and neuronal function at the early stages of disease progression, before neurons die. Here we review the current understanding of how tau-mediated synaptic and neuronal dysfunction contributes to cognitive decline. Delineating the mechanisms by which pathogenic tau alters synapses, dendrites and axons will help lay the foundation for new strategies that can restore neuronal function in tauopathy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship

Anesthesia and Tau Pathology

PubMed Central

Whittington, Robert A.; Bretteville, Alexis; Dickler, Maya F.; Planel, Emmanuel

2013-01-01

Alzheimer’s disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration. PMID:23535147

High-Contrast Near-Infrared Imaging Polarimetry of the Protoplanetary Disk around RY Tau

NASA Technical Reports Server (NTRS)

Takami, Michihiro; Karr, Jennifer L.; Hashimoto, Jun; Kim, Hyosun; Wisenewski, John; Henning, Thomas; Grady, Carol; Kandori, Ryo; Hodapp, Klaus W.; Kudo, Tomoyuki;

Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.

PubMed

Dai, Chun-ling; Chen, Xia; Kazim, Syed Faraz; Liu, Fei; Gong, Cheng-Xin; Grundke-Iqbal, Inge; Iqbal, Khalid

2015-04-01

Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, Aβ accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce Aβ pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce Aβ pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.

ELISA measurement of specific antibodies to phosphorylated tau in intravenous immunoglobulin products.

PubMed

Loeffler, David A; Klaver, Andrea C; Coffey, Mary P

2015-10-01

The therapeutic effects of intravenous immunoglobulin (IVIG) products were recently studied in Alzheimer's disease (AD) patients. Pilot studies produced encouraging results but phase II and III trials gave disappointing results; a further study is in progress. IVIG products contain antibodies to tau protein, the main component of neurofibrillary tangles (NFTs). The tau used to detect IVIG's anti-tau antibodies in previous studies was non-phosphorylated recombinant human tau-441, but NFT-associated tau is extensively phosphorylated. The objective of this study was to determine if various IVIG products contain specific antibodies to phosphorylated tau (anti-pTau antibodies). ELISAs were used to evaluate binding of six IVIG products to a 12 amino acid peptide, tau 196-207, which was phosphorylated ("pTau peptide") or non-phosphorylated ("non-pTau peptide") at Serine-199 and Serine-202. Both amino acid residues are phosphorylated in AD NFTs. Each IVIG's "anti-pTau antibody ratio" was calculated by dividing its binding to the pTau peptide by its binding to the non-pTau peptide. Seven experiments were performed and data were pooled, with each experiment contributing one data point from each IVIG product. Mean anti-pTau antibody ratios greater than 1.0, suggesting specific antibodies to phosphorylated tau, were found for three IVIG products. Because administration of antibodies to phosphorylated tau has been found to reduce tau-associated pathology in transgenic mouse models of tauopathy, increasing the levels of anti-pTau antibodies, together with other selected antibodies such as anti-Aβ, in IVIG might increase its ability to slow AD's progression. Copyright © 2015 Elsevier B.V. All rights reserved.

Disentangling Hadronic and Leptonic Cascade Scenarios from the Very-High-Energy Gamma-Ray Emission of Distant Hard-Spectrum Blazars

DOE PAGES

Takami, Hajime; Murase, Kohta; Dermer, Charles D.

2013-06-26

We show that recent data from the Fermi Large Area Telescope have revealed about a dozen distant hard-spectrum blazars that have very-high-energy (VHE; ≳ 100 eV) photons associated with them, but most of them have not yet been detected by imaging atmospheric Cherenkov Telescopes. Most of these high-energy gamma-ray spectra, like those of other extreme high-frequency peaked BL Lac objects, can be well explained either by gamma rays emitted at the source or by cascades induced by ultra-high-energy cosmic rays, as we show specifically for KUV 00311–1938. We consider the prospects for detection of the VHE sources by the plannedmore » Cherenkov Telescope Array (CTA) and show how it can distinguish the two scenarios by measuring the integrated flux above ~500 GeV (depending on source redshift) for several luminous sources with z ≲ 1 in the sample. Strong evidence for the origin of ultra-high-energy cosmic rays could be obtained from VHE observations with CTA. Depending on redshift, if the often quoted redshift of KUV 00311–1938 (z = 0.61) is believed, then preliminary H.E.S.S. data favor cascades induced by ultra-high-energy cosmic rays. Lastly, accurate redshift measurements of hard-spectrum blazars are essential for this study.« less

A hadronic origin for ultra-high-frequency-peaked BL Lac objects

NASA Astrophysics Data System (ADS)

Cerruti, M.; Zech, A.; Boisson, C.; Inoue, S.

2015-03-01

Current Cherenkov telescopes have identified a population of ultra-high-frequency peaked BL Lac objects (UHBLs), also known as extreme blazars, that exhibit exceptionally hard TeV spectra, including 1ES 0229+200, 1ES 0347-121, RGB J0710+591, 1ES 1101-232, and 1ES 1218+304. Although one-zone synchrotron-self-Compton (SSC) models have been generally successful in interpreting the high-energy emission observed in other BL Lac objects, they are problematic for UHBLs, necessitating very large Doppler factors and/or extremely high minimum Lorentz factors of the emitting leptonic population. In this context, we have investigated alternative scenarios where hadronic emission processes are important, using a newly developed (lepto-)hadronic numerical code to systematically explore the physical parameters of the emission region that reproduces the observed spectra while avoiding the extreme values encountered in pure SSC models. Assuming a fixed Doppler factor δ = 30, two principal parameter regimes are identified, where the high-energy emission is due to: (1) proton-synchrotron radiation, with magnetic fields B ˜ 1-100 G and maximum proton energies Ep; max ≲ 1019 eV; and (2) synchrotron emission from p-γ-induced cascades as well as SSC emission from primary leptons, with B ˜ 0.1-1 G and Ep; max ≲ 1017 eV. This can be realized with plausible, sub-Eddington values for the total (kinetic plus magnetic) power of the emitting plasma, in contrast to hadronic interpretations for other blazar classes that often warrant highly super-Eddington values.

Magnetically Induced Disk Winds and Transport in the HL Tau Disk

NASA Astrophysics Data System (ADS)

Hasegawa, Yasuhiro; Okuzumi, Satoshi; Flock, Mario; Turner, Neal J.

2017-08-01

The mechanism of angular momentum transport in protoplanetary disks is fundamental to understanding the distributions of gas and dust in the disks. The unprecedented ALMA observations taken toward HL Tau at high spatial resolution and subsequent radiative transfer modeling reveal that a high degree of dust settling is currently achieved in the outer part of the HL Tau disk. Previous observations, however, suggest a high disk accretion rate onto the central star. This configuration is not necessarily intuitive in the framework of the conventional viscous disk model, since efficient accretion generally requires a high level of turbulence, which can suppress dust settling considerably. We develop a simplified, semi-analytical disk model to examine under what condition these two properties can be realized in a single model. Recent, non-ideal MHD simulations are utilized to realistically model the angular momentum transport both radially via MHD turbulence and vertically via magnetically induced disk winds. We find that the HL Tau disk configuration can be reproduced well when disk winds are properly taken into account. While the resulting disk properties are likely consistent with other observational results, such an ideal situation can be established only if the plasma β at the disk midplane is β 0 ≃ 2 × 104 under the assumption of steady accretion. Equivalently, the vertical magnetic flux at 100 au is about 0.2 mG. More detailed modeling is needed to fully identify the origin of the disk accretion and quantitatively examine plausible mechanisms behind the observed gap structures in the HL Tau disk.

Vacuum Bloch-Siegert shift in Landau polaritons with ultra-high cooperativity

NASA Astrophysics Data System (ADS)

Li, Xinwei; Bamba, Motoaki; Zhang, Qi; Fallahi, Saeed; Gardner, Geoff C.; Gao, Weilu; Lou, Minhan; Yoshioka, Katsumasa; Manfra, Michael J.; Kono, Junichiro

2018-06-01

A two-level system resonantly interacting with an a.c. magnetic or electric field constitutes the physical basis of diverse phenomena and technologies. However, Schrödinger's equation for this seemingly simple system can be solved exactly only under the rotating-wave approximation, which neglects the counter-rotating field component. When the a.c. field is sufficiently strong, this approximation fails, leading to a resonance-frequency shift known as the Bloch-Siegert shift. Here, we report the vacuum Bloch-Siegert shift, which is induced by the ultra-strong coupling of matter with the counter-rotating component of the vacuum fluctuation field in a cavity. Specifically, an ultra-high-mobility two-dimensional electron gas inside a high-Q terahertz cavity in a quantizing magnetic field revealed ultra-narrow Landau polaritons, which exhibited a vacuum Bloch-Siegert shift up to 40 GHz. This shift, clearly distinguishable from the photon-field self-interaction effect, represents a unique manifestation of a strong-field phenomenon without a strong field.

Ultra high vacuum seal arrangement

DOEpatents

Flaherty, Robert

1981-01-01

Arrangement for demountably sealing two concentric metallic tubes in an ultra high vacuum system which facilitates remote actuation. A tubular seal includes integral spaced lips which circumferentially engage the metallic tubes. The lips plastically deform the metallic tubes by mechanical forces resulting from a martensite to austenite transformation of the tubular seal upon application of a predetermined temperature. The sealing force is released upon application of another temperature which causes a transformation from the stronger austenite to the weaker martensite. Use of a dual acting sealing ring and driving ring circumferentially contacting the sealing ring is particularly applicable to sealing larger diameter concentric metallic members.

Analysis of spectra of V471 Tau and HD 115404

NASA Astrophysics Data System (ADS)

Shimansky, V. V.; Bikmaev, I. F.; Shimanskaya, N. N.

2011-10-01

We analyze the chemical composition of the atmospheres of a single K-type star HD 115404 and the secondary component of the V471 Tau variable. We use the technique of modeling of synthetic spectra to analyze the high-resolution spectra of these stars, taken with the RTT 150 Russian-Turkish telescope and find the abundances of 23 and 17 elements in the atmospheres of HD 115404 and V471 Tau, respectively. We demonstrate the lack of composition anomalies in the HD 115404 and show it to be consistent with the published data, inferred from equivalent widths of spectral lines. We find the abundances of 15 elements from Na to Ba to be consistent with the metallicity of the atmosphere of V471 Tau ([Fe/H] = -0.22 ± 0.12dex), which differs significantly from the average metallicity of the Hyades cluster. We show the existence of strong carbon and oxygen overabundances (by more than 1dex) due to the enrichment of the secondary by the nucleosynthesis products during the common-envelope stage of the system. On the whole, we demonstrate that V471 Tau and the other precataclysmic variables share similar composition anomalies.

Discovering Tau and Muon Solar Neutrino Flares above Backgrounds

NASA Astrophysics Data System (ADS)

Fargion, D.; Moscato, F.

2005-01-01

Solar neutrino flares astronomy is at the edge of its discover. High energy flare particles (protons, alpha) whose self scattering within the solar corona is source of a rich prompt charged pions are also source of sharp solar neutrino "burst" (at tens-hundred MeV) produced by their pion-muon primary decay in flight. This brief (minute) solar neutrino "burst" at largest peak overcome by four-five order of magnitude the steady atmospheric neutrino noise at the Earth. Later on, solar flare particles hitting the terrestrial atmosphere may marginally increase the atmospheric neutrino flux without relevant consequences. Largest prompt "burst" solar neutrino flare may be detected in present or better in future largest neutrino underground neutrino detectors. Our estimate for the recent and exceptional October - November 2003 solar flares gives a number of events above or just near unity for Super-Kamiokande. The neutrino spectra may reflect in a subtle way the neutrino flavour mixing in flight. A surprising tau appearance may even occur for a hard ({E}_{nu}_{mu}--> {E}_{nu}_{tau} > 4 GeV) flare spectra. A comparison of the solar neutrino flare (at their birth place on Sun and after oscillation on the arrival on the Earth) with other neutrino foreground is here described and it offer an independent road map to disentangle the neutrino flavour puzzles and its secret flavour mixing angles .

In Vivo Imaging of Tau Pathology Using Magnetic Resonance Imaging Textural Analysis

PubMed Central

Colgan, Niall; Ganeshan, Balaji; Harrison, Ian F.; Ismail, Ozama; Holmes, Holly E.; Wells, Jack A.; Powell, Nick M.; O'Callaghan, James M.; O'Neill, Michael J.; Murray, Tracey K.; Ahmed, Zeshan; Collins, Emily C.; Johnson, Ross A.; Groves, Ashley; Lythgoe, Mark F.

2017-01-01

Background: Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden. Methods: MRTA was applied to T2 weighted high-resolution MR images of nine 8.5-month-old rTg4510 tau pathology (TG) mice and 16 litter matched wild-type (WT) mice. MRTA comprised of the filtration-histogram technique, where the filtration step extracted and enhanced features of different sizes (fine, medium, and coarse texture scales), followed by quantification of texture using histogram analysis (mean gray level intensity, mean intensity, entropy, uniformity, skewness, standard-deviation, and kurtosis). MRTA was applied to manually segmented regions of interest (ROI) drawn within the cortex, hippocampus, and thalamus regions and the level of tau burden was assessed in equivalent regions using histology. Results: Texture parameters were markedly different between WT and TG in the cortex (E, p < 0.01, K, p < 0.01), the hippocampus (K, p < 0.05) and in the thalamus (K, p < 0.01). In addition, we observed significant correlations between histological measurements of tau burden and kurtosis in the cortex, hippocampus and thalamus. Conclusions: MRTA successfully differentiated WT and TG in brain regions with varying degrees of tau pathology (cortex, hippocampus, and thalamus) based on T2 weighted MR images. Furthermore, the kurtosis measurement correlated with histological measures of tau burden. This initial study indicates that MRTA may have a role in the early diagnosis of AD and the assessment of tau pathology using routinely

Design of Ultra-High-Power-Density Machine Optimized for Future Aircraft

NASA Technical Reports Server (NTRS)

Choi, Benjamin B.

2004-01-01

The NASA Glenn Research Center's Structural Mechanics and Dynamics Branch is developing a compact, nonpolluting, bearingless electric machine with electric power supplied by fuel cells for future "more-electric" aircraft with specific power in the projected range of 50 hp/lb, whereas conventional electric machines generate usually 0.2 hp/lb. The use of such electric drives for propulsive fans or propellers depends on the successful development of ultra-high-power-density machines. One possible candidate for such ultra-high-power-density machines, a round-rotor synchronous machine with an engineering current density as high as 20,000 A/sq cm, was selected to investigate how much torque and power can be produced.

Measurement of the {ital {tau}} Neutrino Helicity and Michel Parameters in Polarized {ital e}{sup +}{ital e}{sup -} Collisions

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

Steiner, R.; Benvenuti, A.C.; Coller, J.A.

1997-06-01

We present a new measurement of the {tau} neutrino helicity h{sub {nu}{sub {tau}}} and the {tau} Michel parameters {rho} , {eta} , {xi} , and the product {delta}{xi} . The analysis exploits the highly polarized SLC electron beam to extract these quantities directly from a measurement of the {tau} decay spectra, using the 1993{endash}1995 SLD data sample of 4328 e{sup +}e{sup -}{r_arrow}Z{sup 0}{r_arrow}{tau}{sup +}{tau}{sup -} events. From the decays {tau}{r_arrow}{pi}{nu}{sub {tau}} and {tau}{r_arrow}{rho}{nu}{sub {tau}} we obtain a combined value h{sub {nu}{sub {tau}}}=-0.93{plus_minus}0.10{plus_minus} 0.04 . The leptonic decay channels yield combined values of {rho}=0.72{plus_minus}0.09{plus_minus}0.03 , {xi}=1.05{plus_minus}0.35{plus_minus}0.04 , and {delta}{xi}=0.88{plus_minus}0.27{plus_minus}0.04 . {copyright}more » {ital 1997} {ital The American Physical Society}« less

Harnessing the immune system for treatment and detection of tau pathology.

PubMed

Congdon, Erin E; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M

2014-01-01

The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future.

BAG3 facilitates the clearance of endogenous tau in primary neurons.

PubMed

Lei, Zhinian; Brizzee, Corey; Johnson, Gail V W

2015-01-01

Tau is a microtubule associated protein that is found primarily in neurons, and in pathologic conditions, such as Alzheimer's disease (AD) it accumulates and contributes to the disease process. Because tau plays a fundamental role in the pathogenesis of AD and other tauopathies, and in AD mouse models reducing tau levels improves outcomes, approaches that facilitate tau clearance are being considered as therapeutic strategies. However, fundamental to the development of such interventions is a clearer understanding of the mechanisms that regulate tau clearance. Here, we report a novel mechanism of tau degradation mediated by the co-chaperone BAG3. BAG3 has been shown to be an essential component of a complex that targets substrates to the autophagy pathway for degradation. In rat primary neurons, activation of autophagy by inhibition of proteasome activity or treatment with trehalose resulted in significant decreases in tau and phospho-tau levels. These treatments also induced an upregulation of BAG3. Proteasome inhibition activated JNK, which was responsible for the upregulation of BAG3 and increased tau clearance. Inhibiting JNK or knocking down BAG3 blocked the proteasome inhibition-induced decreases in tau. Further, BAG3 overexpression alone resulted in significant decreases in tau and phospho-tau levels in neurons. These results indicate that BAG3 plays a critical role in regulating the levels of tau in neurons, and interventions that increase BAG3 levels could provide a therapeutic approach in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

High-energy asymmetric supercapacitors based on free-standing hierarchical Co-Mo-S nanosheets with enhanced cycling stability.

PubMed

Balamurugan, Jayaraman; Li, Chao; Peera, Shaik Gouse; Kim, Nam Hoon; Lee, Joong Hee

2017-09-21

Layered transition metal sulfides (TMS) are emerging as advanced materials for energy storage and conversion applications. In this work, we report a facile and cost-effective anion exchange technique to fabricate a layered, multifaceted, free standing, ultra-thin ternary cobalt molybdenum sulfide nanosheet (Co-Mo-S NS) architecture grown on a 3D porous Ni foam substrate. The unique Co-Mo layered double hydroxides are first synthesized as precursors and consequently transformed into ultra-thin Co-Mo-S NS. When employed as an electrode for supercapacitors, the Co-Mo-S NS delivered an ultra-high specific capacitance of 2343 F g -1 at a current density of 1 mA cm -2 with tremendous rate capability and extraordinary cycling performance (96.6% capacitance retention after 20 000 cycles). Furthermore, assembled Co-Mo-S/nitrogen doped graphene nanosheets (NGNS) in an asymmetric supercapacitor (ASC) device delivered an excellent energy density of 89.6 Wh kg -1 , an amazing power density of 20.07 kW kg -1 , and superior cycling performance (86.8% capacitance retention after 50 000 cycles). Such exceptional electrochemical performance of Co-Mo-S NS is ascribed to the good electrical contact with the 3D Ni foam, ultra-high contact area with the electrolyte, and enhanced architectural softening during the charging/discharging process. It is expected that the fabricated, unique, ultra-thin Co-Mo-S NS have great potential for future energy storage devices.

Comprehensive approach to tau-lepton production by high-energy tau neutrinos propagating through the Earth

NASA Astrophysics Data System (ADS)

Alvarez-Muñiz, Jaime; Carvalho, Washington R.; Payet, Kévin; Romero-Wolf, Andrés; Schoorlemmer, Harm; Zas, Enrique

2018-01-01

There has been a recent surge in interest in the detection of τ -lepton-induced air showers from detectors at altitude. When a τ neutrino (ντ) enters the Earth, it produces τ leptons as a result of nuclear charged-current interactions. In some cases, this process results in a τ lepton exiting the surface of the Earth, which can subsequently decay in the atmosphere and produce an extensive air shower. These upward-going air showers can be detected via fluorescence, optical Cherenkov, or geomagnetic radio emission. Several experiments have been proposed to detect these signals. We present a comprehensive simulation of the production of τ leptons by ντ's propagating through Earth to aid the design of future experiments. These simulations for ντ's and leptons in the energy range from 1 015 eV to 1 021 eV treat the full range of incidence angles from Earth-skimming to diametrically traversing. Propagation of ντ's and leptons includes the effects of rock and an ocean or ice layer of various thicknesses. The interaction models include ντ regeneration and account for uncertainties in the Standard Model neutrino cross section and in the photonuclear contribution to the τ energy-loss rate.

Phosphorylation of Threonine 175 Tau in the Induction of Tau Pathology in Amyotrophic Lateral Sclerosis-Frontotemporal Spectrum Disorder (ALS-FTSD). A Review.

PubMed

Moszczynski, Alexander J; Hintermayer, Matthew A; Strong, Michael J

2018-01-01

Approximately 50-60% of all patients with amyotrophic lateral sclerosis (ALS) will develop a deficit of frontotemporal function, ranging from frontotemporal dementia (FTD) to one or more deficits of neuropsychological, speech or language function which are collectively known as the frontotemporal spectrum disorders of ALS (ALS-FTSD). While the neuropathology underlying these disorders is most consistent with a widespread alteration in the metabolism of transactive response DNA-binding protein 43 (TDP-43), in both ALS with cognitive impairment (ALSci) and ALS with FTD (ALS-FTD; also known as MND-FTD) there is evidence for alterations in the metabolism of the microtubule associated protein tau. This alteration in tau metabolism is characterized by pathological phosphorylation at residue Thr 175 (pThr 175 tau) which in vitro is associated with activation of GSK3β (pTyr 216 GSK3β), phosphorylation of Thr 231 tau, and the formation of cytoplasmic inclusions with increased rates of cell death. This putative pathway of pThr 175 induction of pThr 231 and the formation of pathogenic tau inclusions has been recently shown to span a broad range of tauopathies, including chronic traumatic encephalopathy (CTE) and CTE in association with ALS (CTE-ALS). This pathway can be experimentally triggered through a moderate traumatic brain injury, suggesting that it is a primary neuropathological event and not secondary to a more widespread neuronal dysfunction. In this review, we discuss the neuropathological underpinnings of the postulate that ALS is associated with a tauopathy which manifests as a FTSD, and examine possible mechanisms by which phosphorylation at Thr 175 tau is induced. We hypothesize that this might lead to an unfolding of the hairpin structure of tau, activation of GSK3β and pathological tau fibril formation through the induction of cis -Thr 231 tau conformers. A potential role of TDP-43 acting synergistically with pathological tau metabolism is proposed.

Ultra-high-mass mass spectrometry with charge discrimination using cryogenic detectors

DOEpatents

Frank, Matthias; Mears, Carl A.; Labov, Simon E.; Benner, W. Henry

1999-01-01

An ultra-high-mass time-of-flight mass spectrometer using a cryogenic particle detector as an ion detector with charge discriminating capabilities. Cryogenic detectors have the potential for significantly improving the performance and sensitivity of time-of-flight mass spectrometers, and compared to ion multipliers they exhibit superior sensitivity for high-mass, slow-moving macromolecular ions and can be used as "stop" detectors in time-of-flight applications. In addition, their energy resolving capability can be used to measure the charge state of the ions. Charge discrimination is very valuable in all time-of-flight mass spectrometers. Using a cryogenically-cooled Nb-Al.sub.2 O.sub.3 -Nb superconductor-insulator-superconductor (SIS) tunnel junction (STJ) detector operating at 1.3 K as an ion detector in a time-of-flight mass spectrometer for large biomolecules it was found that the STJ detector has charge discrimination capabilities. Since the cryogenic STJ detector responds to ion energy and does not rely on secondary electron production, as in the conventionally used microchannel plate (MCP) detectors, the cryogenic detector therefore detects large molecular ions with a velocity-independent efficiency approaching 100%.

The ELISA-measured increase in cerebrospinal fluid tau that discriminates Alzheimer's disease from other neurodegenerative disorders is not attributable to differential recognition of tau assembly forms.

PubMed

O'Dowd, Seán T; Ardah, Mustafa T; Johansson, Per; Lomakin, Aleksey; Benedek, George B; Roberts, Kinley A; Cummins, Gemma; El Agnaf, Omar M; Svensson, Johan; Zetterberg, Henrik; Lynch, Timothy; Walsh, Dominic M

2013-01-01

Elevated cerebrospinal fluid concentrations of tau discriminate Alzheimer's disease from other neurodegenerative conditions. The reasons for this are unclear. While commercial assay kits are widely used to determine total-tau concentrations, little is known about their ability to detect different aggregation states of tau. We demonstrate that the leading commercial enzyme-linked immunosorbent assay reliably detects aggregated and monomeric tau and evinces good recovery of both species when added into cerebrospinal fluid. Hence, the disparity between total-tau levels encountered in Alzheimer's disease and other neurodegenerative conditions is not due to differential recognition of tau assembly forms or the extent of degeneration.

UX Tau A

NASA Technical Reports Server (NTRS)

2007-01-01

This is an artist's rendition of the one-million-year-old star system called UX Tau A, located approximately 450 light-years away. Observations from NASA's Spitzer Space Telescope showed a gap in the dusty planet-forming disk swirling around the system's central sun-like star.

Spitzer saw a gap in UX Tau A's disk that extends from 0.2 to 56 astronomical units (an astronomical unit is the distance between the sun and Earth). The gap extends from the equivalent of Mercury to Pluto in our solar system, and is sandwiched between thick inner and outer disks on either side. Astronomers suspect that the gap was carved out by one or more forming planets.

Such dusty disks are where planets are thought to be born. Dust grains clump together like snowballs to form larger rocks, and then the bigger rocks collide to form the cores of planets. When rocks revolve around their central star, they act like cosmic vacuum cleaners, picking up all the gas and dust in their path and creating gaps.

Although gaps have been detected in disks swirling around young stars before, UX Tau A is special because the gap is sandwiched between two thick disks of dust. An inner thick dusty disk hugs the central star, then, moving outward, there is a gap, followed by another thick doughnut-shaped disk. Other systems with gaps contain very little to no dust near the central star. In other words, those gaps are more like big holes in the centers of disks.

Some scientists suspect that these holes could have been carved out by a process called photoevaporation. Photoevaporation occurs when radiation from the central star heats up the gas and dust around it to the point where it evaporates away. The fact that there is thick disk swirling extremely close to UX Tau A's central star rules out the photoevaporation scenario. If photoevaporation from the star played a role, then large amounts of dust would not be floating so close to the star.

Spatially-Resolved Characterization Techniques to Investigate Impact Damage in Ultra-High Performance Concretes

DTIC Science & Technology

2013-04-01

Concretes G eo te ch n ic al a n d S tr u ct u re s La b or at or y Robert D. Moser, Paul G. Allison, and Mei Q. Chandler April 2013 Approved...Impact Damage in Ultra-High Performance Concretes Robert D. Moser, Paul G. Allison, and Mei Q. Chandler Geotechnical and Structures Laboratory US...Portland Cement concrete (OPC) and Ultra-High Performance Concretes (UHPCs) under high-strain impact and penetration loads at lower length scales

Interplay of pathogenic forms of human tau with different autophagic pathways.

PubMed

Caballero, Benjamin; Wang, Yipeng; Diaz, Antonio; Tasset, Inmaculada; Juste, Yves Robert; Stiller, Barbara; Mandelkow, Eva-Maria; Mandelkow, Eckhard; Cuervo, Ana Maria

2018-02-01

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients' brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age-related disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk-associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway. We also found defective autophagic degradation of tau when using mutations that mimic common posttranslational modifications in tau or known to promote its aggregation. Interestingly, although most mutations markedly reduced degradation of tau through autophagy, the step of this process preferentially affected varies depending on the type of tau mutation. Overall, our studies unveil a complex interplay between the multiple modifications of tau and selective forms of autophagy that may determine its physiological degradation and its faulty clearance in the disease context. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Transparent Ultra-High-Loading Quantum Dot/Polymer Nanocomposite Monolith for Gamma Scintillation.

PubMed

Liu, Chao; Li, Zhou; Hajagos, Tibor Jacob; Kishpaugh, David; Chen, Dustin Yuan; Pei, Qibing

2017-06-27

Spectroscopic gamma-photon detection has widespread applications for research, defense, and medical purposes. However, current commercial detectors are either prohibitively expensive for wide deployment or incapable of producing the characteristic gamma photopeak. Here we report the synthesis of transparent, ultra-high-loading (up to 60 wt %) Cd x Zn 1-x S/ZnS core/shell quantum dot/polymer nanocomposite monoliths for gamma scintillation by in situ copolymerization of the partially methacrylate-functionalized quantum dots in a monomer solution. The efficient Förster resonance energy transfer of the high-atomic-number quantum dots to lower-band-gap organic dyes enables the extraction of quantum-dot-borne excitons for photon production, resolving the problem of severe light yield deterioration found in previous nanoparticle-loaded scintillators. As a result, the nanocomposite scintillator exhibited simultaneous improvements in both light yield (visible photons produced per MeV of gamma-photon energy) and gamma attenuation. With these enhancements, a 662 keV Cs-137 gamma photopeak with 9.8% resolution has been detected using a 60 wt % quantum-dot nanocomposite scintillator, demonstrating the potential of such a nanocomposite system in the development of high-performance low-cost spectroscopic gamma detectors.

Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy

PubMed Central

Kanaan, Nicholas M.; Cox, Kristine; Alvarez, Victor E.; Stein, Thor D.; Poncil, Sharra; McKee, Ann C.

2016-01-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. PMID:26671985

Tau Ranging Revisited

NASA Technical Reports Server (NTRS)

Tausworthe, Robert C.

1989-01-01

Report reviews history of tau ranging and advocates use of advanced electronic circuitry to revive this composite-code-uplink spacecraft-ranging technique. Very-large-scale integration gives new life to abandoned distance-measuring technique.

Estimative of conversion fractions of AGN magnetic luminosity to produce ultra high energy cosmic rays from the observation of Fermi-LAT gamma rays

NASA Astrophysics Data System (ADS)

Coimbra-Araújo, Carlos H.; Anjos, Rita C.

2017-01-01

A fraction of the magnetic luminosity (LB) produced by Kerr black holes in some active galactic nuclei (AGNs) can produce the necessary energy to accelerate ultra high energy cosmic rays (UHECRs) beyond the GZK limit, observed, e.g., by the Pierre Auger experiment. Nevertheless, the direct detection of those UHECRs has a lack of information about the direction of the source from where those cosmic rays are coming, since charged particles are deflected by the intergalactic magnetic field. This problem arises the needing of alternative methods to evaluate the luminosity of UHECRs (LCR) from a given source. Methods proposed in literature range from the observation of upper limits in gamma rays to the observation of upper limits in neutrinos produced by cascade effects during the propagation of UHECRs. In this aspect, the present work proposes a method to calculate limits of the main possible conversion fractions ηCR = LCR/LB for nine UHECR AGN Seyfert sources based on the respective observation of gamma ray upper limits from Fermi-LAT data.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Depletion of microglia and inhibition of exosome synthesis halt tau propagation

PubMed Central

Asai, Hirohide; Ikezu, Seiko; Tsunoda, Satoshi; Medalla, Maria; Luebke, Jennifer; Haydar, Tarik; Wolozin, Benjamin; Butovsky, Oleg; Kügler, Sebastian; Ikezu, Tsuneya

2015-01-01

Accumulation of pathological tau protein is a major hallmark of Alzheimer’s disease. Tau protein spreads from the entorhinal cortex to the hippocampal region early in the disease. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology, but their involvement in tau propagation is unknown. We developed an adeno-associated virus–based model exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus in 4 weeks. We found that depleting microglia dramatically suppressed the propagation of tau and reduced excitability in the dentate gyrus in this mouse model. Moreover, we demonstrate that microglia spread tau via exosome secretion, and inhibiting exosome synthesis significantly reduced tau propagation in vitro and in vivo. These data suggest that microglia and exosomes contribute to the progression of tauopathy and that the exosome secretion pathway may be a therapeutic target. PMID:26436904

Longitudinal tau PET in ageing and Alzheimer’s disease

PubMed Central

Jack, Clifford R; Wiste, Heather J; Schwarz, Christopher G; Lowe, Val J; Senjem, Matthew L; Vemuri, Prashanthi; Weigand, Stephen D; Therneau, Terry M; Knopman, Dave S; Gunter, Jeffrey L; Jones, David T; Graff-Radford, Jonathan; Kantarci, Kejal; Roberts, Rosebud O; Mielke, Michelle M; Machulda, Mary M; Petersen, Ronald C

2018-01-01

Abstract See Hansson and Mormino (doi:10.1093/brain/awy065) for a scientific commentary on this article. Our objective was to compare different whole-brain and region-specific measurements of within-person change on serial tau PET and evaluate its utility for clinical trials. We studied 126 individuals: 59 cognitively unimpaired with normal amyloid, 37 cognitively unimpaired with abnormal amyloid, and 30 cognitively impaired with an amnestic phenotype and abnormal amyloid. All had baseline amyloid PET and two tau PET, MRI, and clinical assessments. We compared the topography across all cortical regions of interest of tau PET accumulation rates and the rates of four different whole-brain or region-specific meta-regions of interest among the three clinical groups. We computed sample size estimates for change in tau PET, cortical volume, and memory/mental status indices for use as outcome measures in clinical trials. The cognitively unimpaired normal amyloid group had no observable tau accumulation throughout the brain. Tau accumulation rates in cognitively unimpaired abnormal amyloid were low [0.006 standardized uptake value ratio (SUVR), 0.5%, per year] but greater than rates in the cognitively unimpaired normal amyloid group in the basal and mid-temporal, retrosplenial, posterior cingulate, and entorhinal regions of interest. Thus, the earliest elevation in accumulation rates was widespread and not confined to the entorhinal cortex. Tau accumulation rates in the cognitively impaired abnormal amyloid group were 0.053 SUVR (3%) per year and greater than rates in cognitively unimpaired abnormal amyloid in all cortical areas except medial temporal. Rates of accumulation in the four meta-regions of interest differed but only slightly from one another. Among all tau PET meta-regions of interest, sample size estimates were smallest for a temporal lobe composite within cognitively unimpaired abnormal amyloid and for the late Alzheimer’s disease meta-region of interest

Ultra-high density diffraction grating

DOEpatents

Padmore, Howard A.; Voronov, Dmytro L.; Cambie, Rossana; Yashchuk, Valeriy V.; Gullikson, Eric M.

2012-12-11

A diffraction grating structure having ultra-high density of grooves comprises an echellette substrate having periodically repeating recessed features, and a multi-layer stack of materials disposed on the echellette substrate. The surface of the diffraction grating is planarized, such that layers of the multi-layer stack form a plurality of lines disposed on the planarized surface of the structure in a periodical fashion, wherein lines having a first property alternate with lines having a dissimilar property on the surface of the substrate. For example, in one embodiment, lines comprising high-Z and low-Z materials alternate on the planarized surface providing a structure that is suitable as a diffraction grating for EUV and soft X-rays. In some embodiments, line density of between about 10,000 lines/mm to about 100,000 lines/mm is provided.

Clustering-based energy-saving algorithm in ultra-dense network

NASA Astrophysics Data System (ADS)

Huang, Junwei; Zhou, Pengguang; Teng, Deyang; Zhang, Renchi; Xu, Hao

2017-06-01

In Ultra-dense Networks (UDN), dense deployment of low power small base stations will cause serious small cells interference and a large amount of energy consumption. The purpose of this paper is to explore the method of reducing small cells interference and energy saving system in UDN, and we innovatively propose a sleep-waking-active (SWA) scheme. The scheme decreases the user outage causing by failure to detect users’ service requests, shortens the opening time of active base stations directly switching to sleep mode; we further proposes a Vertex Surrounding Clustering(VSC) algorithm, which first colours the small cells with the most strongest interference and next extends to the adjacent small cells. VSC algorithm can use the least colour to stain the small cell, reduce the number of iterations and promote the efficiency of colouring. The simulation results show that SWA scheme can effectively improve the system Energy Efficiency (EE), the VSC algorithm can reduce the small cells interference and optimize the users’ Spectrum Efficiency (SE) and throughput.

Ultra-bright γ-ray flashes and dense attosecond positron bunches from two counter-propagating laser pulses irradiating a micro-wire target.

PubMed

Li, Han-Zhen; Yu, Tong-Pu; Hu, Li-Xiang; Yin, Yan; Zou, De-Bin; Liu, Jian-Xun; Wang, Wei-Quan; Hu, Shun; Shao, Fu-Qiu

2017-09-04

We propose a novel scheme to generate ultra-bright ultra-short γ-ray flashes and high-energy-density attosecond positron bunches by using multi-dimensional particle-in-cell simulations with quantum electrodynamics effects incorporated. By irradiating a 10 PW laser pulse with an intensity of 10 23 W/cm 2 onto a micro-wire target, surface electrons are dragged-out of the micro-wire and are effectively accelerated to several GeV energies by the laser ponderomotive force, forming relativistic attosecond electron bunches. When these electrons interact with the probe pulse from the other side, ultra-short γ-ray flashes are emitted with an ultra-high peak brightness of 1.8 × 10 24 photons s -1 mm -2 mrad -2 per 0.1%BW at 24 MeV. These photons propagate with a low divergence and collide with the probe pulse, triggering the Breit-Wheeler process. Dense attosecond e - e + pair bunches are produced with the positron energy density as high as 10 17 J/m 3 and number of 10 9 . Such ultra-bright ultra-short γ-ray flashes and secondary positron beams may have potential applications in fundamental physics, high-energy-density physics, applied science and laboratory astrophysics.

APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

PubMed

Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

2015-05-05

Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

PubMed Central

Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B.; Baillargeon, Joanie; Hébert, Sébastien S.; Planel, Emmanuel

2012-01-01

Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro. PMID:22768202

Tau Oligomers as Pathogenic Seeds: Preparation and Propagation In Vitro and In Vivo.

PubMed

Gerson, Julia E; Sengupta, Urmi; Kayed, Rakez

2017-01-01

Tau oligomers have been shown to be the main toxic tau species in a number of neurodegenerative disorders. In order to study tau oligomers both in vitro and in vivo, we have established methods for the reliable preparation, isolation, and detection of tau oligomers. Methods for the seeding of tau oligomers, isolation of tau oligomers from tissue, and detection of tau oligomers using tau oligomer-specific antibodies by biochemical and immunohistochemical methods are detailed below.

Link and Network Layers Design for Ultra-High-Speed Terahertz-Band Communications Networks

DTIC Science & Technology

2017-01-01

throughput, and identify the optimal parameter values for their design (Sec. 6.2.3). Moreover, we validate and test the scheme with experimental data obtained...LINK AND NETWORK LAYERS DESIGN FOR ULTRA-HIGH- SPEED TERAHERTZ-BAND COMMUNICATIONS NETWORKS STATE UNIVERSITY OF NEW YORK (SUNY) AT BUFFALO JANUARY...TYPE FINAL TECHNICAL REPORT 3. DATES COVERED (From - To) FEB 2015 – SEP 2016 4. TITLE AND SUBTITLE LINK AND NETWORK LAYERS DESIGN FOR ULTRA-HIGH

Stability of the tungsten diselenide and silicon carbide heterostructure against high energy proton exposure

NASA Astrophysics Data System (ADS)

Walker, Roger C.; Shi, Tan; Jariwala, Bhakti; Jovanovic, Igor; Robinson, Joshua A.

2017-10-01

Single layers of tungsten diselenide (WSe2) can be used to construct ultra-thin, high-performance electronics. Additionally, there has been considerable progress in controlled and direct growth of single layers on various substrates. Based on these results, high-quality WSe2-based devices that approach the limit of physical thickness are now possible. Such devices could be useful for space applications, but understanding how high-energy radiation impacts the properties of WSe2 and the WSe2/substrate interface has been lacking. In this work, we compare the stability against high energy proton radiation of WSe2 and silicon carbide (SiC) heterostructures generated by mechanical exfoliation of WSe2 flakes and by direct growth of WSe2 via metal-organic chemical vapor deposition (MOCVD). These two techniques produce WSe2/SiC heterostructures with distinct differences due to interface states generated during the MOCVD growth process. This difference carries over to differences in band alignment from interface states and the ultra-thin nature of the MOCVD-grown material. Both heterostructures are not susceptible to proton-induced charging up to a dose of 1016 protons/cm2, as measured via shifts in the binding energy of core shell electrons and a decrease in the valence band offset. Furthermore, the MOCVD-grown material is less affected by the proton exposure due to its ultra-thin nature and a greater interaction with the substrate. These combined effects show that the directly grown material is suitable for multi-year use in space, provided that high quality devices can be fabricated from it.

Biocompatibility of modified ultra-high-molecular-weight polyethylene

NASA Astrophysics Data System (ADS)

Novotná, Z.; Lacmanová, V.; Rimpelová, S.; Juřik, P.; Polívková, M.; Å vorčik, V.

2016-09-01

Ultra-high-molecular-weight polyethylene (UHMWPE, PE) is a synthetic polymer used for biomedical applications because of its high impact resistance, ductility and stability in contact with physiological fluids. Therefore this material is being used in human orthopedic implants such as total joint replacements. Surface modification of this material relates to changes of its surface hydrophilicity, energy, microstructure, roughness, and morphology, all influencing its biological response. In our recent work, PE was treated by an Ar+ plasma discharge and then grafted with biologically active polyethylene glycol in order to enhance adhesion and proliferation of mouse fibroblast (L929). The surface properties of pristine PE and its grafted counterparts were studied by goniometry (surface wettability). Furthermore, Atomic Force Microscopy was used to determine the surface morphology and roughness. The biological response of the L929 cell lines seeded on untreated and plasma treated PE matrices was quantified in terms of the cell adhesion, density, and metabolic activity. Plasma treatment leads to the ablation of the polymer surface layers. Plasma treatment and subsequent poly(ethylene glycol) grafting lead to dramatic changes in the polymer surface morphology and roughness. Biological tests, performed in vitro, show increased adhesion and proliferation of cells on modified polymers. Grafting with poly(ethylene glycol) increases cell proliferation compared to plasma treatment.

Adaptive sensor-based ultra-high accuracy solar concentrator tracker

NASA Astrophysics Data System (ADS)

Brinkley, Jordyn; Hassanzadeh, Ali

2017-09-01

Conventional solar trackers use information of the sun's position, either by direct sensing or by GPS. Our method uses the shading of the receiver. This, coupled with nonimaging optics design allows us to achieve ultra-high concentration. Incorporating a sensor based shadow tracking method with a two stage concentration solar hybrid parabolic trough allows the system to maintain high concentration with acute accuracy.

Ultra-broadband and planar sound diffuser with high uniformity of reflected intensity

NASA Astrophysics Data System (ADS)

Fan, Xu-Dong; Zhu, Yi-Fan; Liang, Bin; Yang, Jing; Yang, Jun; Cheng, Jian-Chun

2017-09-01

Schroeder diffusers, as a classical design of acoustic diffusers proposed over 40 years ago, play key roles in many practical scenarios ranging from architectural acoustics to noise control to particle manipulation. Despite the great success of conventional acoustic diffusers, it is still worth pursuing ideal acoustic diffusers that are essentially expected to produce perfect sound diffuse reflection within the unlimited bandwidth. Here, we propose a different mechanism for designing acoustic diffusers to overcome the basic limits in intensity uniformity and working bandwidth in the previous designs and demonstrate a practical implementation by acoustic metamaterials with dispersionless phase-steering capability. In stark contrast to the existing production of diffuse fields relying on random scattering of sound energy by using a specific mathematical number sequence of periodically distributed unit cells, we directly mold the reflected wavefront into the desired shape by precisely manipulating the local phases of individual subwavelength metastructures. We also benchmark our design via numerical simulation with a commercially available Schroeder diffuser, and the results verify that our proposed diffuser scatters incident acoustic energy into all directions more uniformly within an ultra-broad band regardless of the incident angle. Furthermore, our design enables further improvement of the working bandwidth just by simply downscaling each individual element. With ultra-broadband functionality and high uniformity of reflected intensity, our metamaterial-based production of the diffusive field opens a route to the design and application of acoustic diffusers and may have a significant impact on various fields such as architectural acoustics and medical ultrasound imaging/treatment.

Magnetically Induced Disk Winds and Transport in the HL Tau Disk

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

Hasegawa, Yasuhiro; Flock, Mario; Turner, Neal J.

2017-08-10

The mechanism of angular momentum transport in protoplanetary disks is fundamental to understanding the distributions of gas and dust in the disks. The unprecedented ALMA observations taken toward HL Tau at high spatial resolution and subsequent radiative transfer modeling reveal that a high degree of dust settling is currently achieved in the outer part of the HL Tau disk. Previous observations, however, suggest a high disk accretion rate onto the central star. This configuration is not necessarily intuitive in the framework of the conventional viscous disk model, since efficient accretion generally requires a high level of turbulence, which can suppressmore » dust settling considerably. We develop a simplified, semi-analytical disk model to examine under what condition these two properties can be realized in a single model. Recent, non-ideal MHD simulations are utilized to realistically model the angular momentum transport both radially via MHD turbulence and vertically via magnetically induced disk winds. We find that the HL Tau disk configuration can be reproduced well when disk winds are properly taken into account. While the resulting disk properties are likely consistent with other observational results, such an ideal situation can be established only if the plasma β at the disk midplane is β {sub 0} ≃ 2 × 10{sup 4} under the assumption of steady accretion. Equivalently, the vertical magnetic flux at 100 au is about 0.2 mG. More detailed modeling is needed to fully identify the origin of the disk accretion and quantitatively examine plausible mechanisms behind the observed gap structures in the HL Tau disk.« less

High-efficiency water-loaded microwave antenna in ultra-high-frequency band

NASA Astrophysics Data System (ADS)

Gong, Zilun; Bartone, Chris; Yang, Fuyi; Yao, Jie

2018-03-01

High-index dielectrics are widely used in microwave antennas to control the radiation characteristics. Liquid water, with a high dielectric index at microwave frequency, is an interesting material to achieving tunable functionalities. Here, we demonstrate a water-loaded microwave antenna system that has high loss-tolerance and wideband tunability enabled by fluidity. Our simulation and experimental results show that the resonance frequency can be effectively tuned by the size of loading water. Furthermore, the antenna systems with water loading can achieve high radiation efficiency (>90%) in the ultra-high-frequency (0.3-3 GHz) band. This work brings about opportunities in realistic tunable microwave antenna designs enabled by liquid.

CO2 induced pHi changes in the brain of polar fish: a TauCEST application.

PubMed

Wermter, Felizitas C; Maus, Bastian; Pörtner, Hans-O; Dreher, Wolfgang; Bock, Christian

2018-06-22

Chemical exchange saturation transfer (CEST) from taurine to water (TauCEST) can be used for in vivo mapping of taurine concentrations as well as for measurements of relative changes in intracellular pH (pH i ) at temperatures below 37°C. Therefore, TauCEST offers the opportunity to investigate acid-base regulation and neurological disturbances of ectothermic animals living at low temperatures, and in particular to study the impact of ocean acidification (OA) on neurophysiological changes of fish. Here, we report the first in vivo application of TauCEST imaging. Thus, the study aimed to investigate the TauCEST effect in a broad range of temperatures (1-37°C) and pH (5.5-8.0), motivated by the high taurine concentration measured in the brains of polar fish. The in vitro data show that the TauCEST effect is especially detectable in the low temperature range and strictly monotonic for the relevant pH range (6.8-7.5). To investigate the specificity of TauCEST imaging for the brain of polar cod (Boreogadus saida) at 1.5°C simulations were carried out, indicating a taurine contribution of about 65% to the in vivo expected CEST effect, if experimental parameters are optimized. B. saida was acutely exposed to three different CO 2 concentrations in the sea water (control normocapnia; comparatively moderate hypercapnia OA m  = 3300 μatm; high hypercapnia OA h  = 4900 μatm). TauCEST imaging of the brain showed a significant increase in the TauCEST effect under the different CO 2 concentrations of about 1.5-3% in comparison with control measurements, indicative of changes in pH i or metabolite concentration. Consecutive recordings of 1 H MR spectra gave no support for a concentration induced change of the in vivo observed TauCEST effect. Thus, the in vivo application of TauCEST offers the possibility of mapping relative changes in pH i in the brain of polar cod during exposure to CO 2 . © 2018 John Wiley & Sons, Ltd.

Cosmic strings and ultra-high energy cosmic rays

NASA Technical Reports Server (NTRS)

Bhattacharjee, Pijushpani

1989-01-01

The flux is calculated of ultrahigh energy protons due to the process of cusp evaporation from cosmic string loops. For the standard value of the dimensionless cosmic string parameter epsilon is identical to G(sub mu) approx. = 10(exp -6), the flux is several orders of magnitude below the observed cosmic ray flux of ultrahigh energy protons. However, the flux at any energy initially increases as the value of epsilon is decreased. This at first suggests that there may be a lower limit on the value of epsilon, which would imply a lower limit on the temperature of a cosmic string forming phase transition in the early universe. However, the calculation shows that this is not the case -- the particle flux at any energy reaches its highest value at epsilon approx. = 10(exp -15) and it then decreases for further decrease of the value of epsilon. This is due to the fact that for too small values of epsilon (less than 10(exp -15)), the energy loss of the loops through the cusp evaporation process itself (rather than gravitational energy loss of the loops) becomes the dominant factor that controls the behavior of the number density of the loops at the relevant times of emission of the particles. The highest flux at any energy remains at least four orders of magnitude below the observed flux. There is thus no lower limit on epsilon.

Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment.

PubMed

Sohn, Peter Dongmin; Tracy, Tara E; Son, Hye-In; Zhou, Yungui; Leite, Renata E P; Miller, Bruce L; Seeley, William W; Grinberg, Lea T; Gan, Li

2016-06-29

Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood. Here we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and βIV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures. Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS.