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Sample records for betatron phase advance

  1. Betatron phase advance measurement at SPEAR

    International Nuclear Information System (INIS)

    Morton, P.L.; Pellegrin, J.L.; Raubenheimer, T.; Ross, M.

    1987-02-01

    There are many reasons to determine the betatron phase advance between two azimuthal positions in a circular accelerator or storage ring. We have measured the betatron phase advance between various pairs of azimuthal points in the SPEAR Storage Ring by two different methods. The first method is to excite a steady state coherent betatron oscillation with a network analyzer. The second method is to excite a free coherent betatron oscillation with an impulse kick, and to digitally sample the transverse position of the beam at the pickup stations. The results of these digital samples are Fourier analyzed with a computer to obtain the phase advance. The second method is discussed, and the experimental results compared to theory

  2. Betatron phase advance measurement at SPEAR

    International Nuclear Information System (INIS)

    Morton, P.L.; Pellegrin, J.L.; Raubenheimer, T.; Ross, M.

    1987-01-01

    There are many reasons to determine the betatron phase advance between two azimuthal positions in a circular accelerator or storage ring. The authors measured the betatron phase advance between various pairs of azimuthal points in the SPEAR Storage Ring by two different methods. The first method is to excite a steady state coherent betatron oscillation with a network analyzer. The second method is to excite a free coherent betatron oscillation with an impulse kick, and to digitally sample the transverse position of the beam at the pickup stations. The results of these digital samples are Fourier analyzed with a computer to obtain the phase advance. The second method is discussed, and the experimental results compared to theory

  3. The effects of betatron phase advances on beam-beam and its compensation in RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Y.; Fischer, W.; Gu, X.; Tepikian, S.; Trbojevic, D.

    2011-03-28

    In this article we perform simulation studies to investigate the effects of betatron phase advances between the beam-beam interaction points on half-integer resonance driving term, second order chromaticty and dynamic aperture in RHIC. The betatron phase advances are adjusted with artificial matrices inserted in the middle of arcs. The lattices for the 2011 RHIC polarized proton (p-p) run and 2010 RHIC Au-Au runs are used in this study. We also scan the betatron phase advances between IP8 and the electron lens for the proposed Blue ring lattice with head-on beam-beam compensation.

  4. Measurement of the betatron phase advance and betatron amplitude ratio at the SPP-barS collider

    International Nuclear Information System (INIS)

    Bossart, R.; Scandale, W.

    1987-01-01

    A technique for the precise measurement of lattice functions in a hadron collider has been developed. The betatron functions on either side of the two low beta insertions of the SPS collider have been determined from the measured amplitude and phase of horizontal beam oscillations with a peak amplitude of 40 μm. Four directional couplers and four synchronous receivers working at 200 MHz monitor the betatron oscillations of the beam excited by the fast deflectors of the damper. A fast Fourier transform of the signals provides the phase and amplitude ratio of the beam oscillations between any pair of monitors. The relative amplitude and phase of the beam oscillations can be measured with an accuracy of 0 in phase. For achieving such an accuracy a special calibration method has been implemented to determine the propagation times and amplification factors of the measuring equipment, using the intensity signals of the beam itself. The same equipment can be used also for measuring the beam transfer function by injecting white noise into the beam deflectors

  5. Synchronisation of the LHC Betatron Coupling and Phase Advance Measurement System

    CERN Document Server

    Gasior, M

    2014-01-01

    The new LHC Diode ORbit and OScillation (DOROS) system will provide beam position readings with submicrometre resolution and at the same time will be able to perform measurements of local betatron coupling and beam phase advance with micrometre beam excitation. The oscillation sub-system employs gain-controlled RF amplifiers, shared with the orbit system, and followed by dedicated diode detectors to demodulate the beam oscillation signals into the kHz frequency range, subsequently digitized by multi-channel 24-bit ADCs. The digital signals are processed in each front-end with an FPGA and the results of reduced throughput are sent using an Ethernet protocol to a common concentrator, together with the orbit data. The phase advance calculation between multiple Beam Position Monitors (BPMs) requires that all DOROS front-ends have a common phase reference. This paper presents methods used to generate such a reference and to maintain a stable synchronous sampling on all system front-ends. The performance of the DOR...

  6. Transverse betatron tune measurements

    International Nuclear Information System (INIS)

    Serio, M.

    1989-01-01

    In this paper the concept of the betatron tune and the techniques to measure it are discussed. The smooth approximation is introduced along with the terminology of betatron oscillations, phase advance and tune. Single particle and beam spectra in the presence of synchro-betatron oscillations are treated with emphasis on the consequences of sampling the beam position. After a general presentation of various kinds of beam position monitors and transverse kickers, the time domain and frequency domain analysis of the beam response to a transverse excitation are discussed and several methods and applications of the tune measurements are listed

  7. The tandem betatron accelerator

    International Nuclear Information System (INIS)

    Keinigs, R.

    1991-01-01

    This paper reports that the tandem betatron is a compact, high-current induction accelerator that has the capability to accelerate electrons to an energy of order one gigavolt. Based upon the operating principle of a conventional betatron, the tandem betatron employs two synchronized induction cores operating 180 degrees out of phase. Embedded within the cores are the vacuum chambers, and these are connected by linear transport sections to allow for moving the beam back and forth between the two betatrons. The 180 degree phase shift between the core fluxes permits the circumvention of the flux swing constraint that limits the maximum energy gain of a conventional betatron. By transporting the beam between the synchronized cores, an electron can access more than one acceleration cycle, and thereby continue to gain energy. This added degree of freedom also permits a significant decrease in the size of the magnet system. Biasing coils provide independent control of the confining magnetic field. Provided that efficient beam switching can be performed, it appears feasible that a one gigavolt electron beam can be generated and confined. At this energy, a high current electron beam circulating in a one meter radius orbit could provide a very intense source of short wavelength (λ < 10 nm) synchrotron radiation. This has direct application to the emerging field of x-ray lithography. At more modest energies (10 MeV-30 MEV) a compact tandem betatron could be employed in the fields of medical radiation therapy, industrial radiography, and materials processing

  8. Energy measurements from betatron oscillations

    International Nuclear Information System (INIS)

    Himel, T.; Thompson, K.

    1989-03-01

    In the Stanford Linear Collider the electron beam is accelerated from 1--50 GeV in a distance of 3 km. The energy is measured and corrected at the end with an energy feedback loop. There are no bends within the linear accelerator itself, so no intermediate energy measurements are made. Errors in the energy profile due to mis-phasing of the rf, or due to calibration errors in the klystrons' rf outputs are difficult to detect. As the total betatron phase advance down the accelerator is about 30 /times/ 2π, an energy error of a few percent can cause a large error in the total phase advance. This in turn degrades the performance of auto-steering programs. We have developed a diagnostic program which generates and measures several betatron oscillations in the accelerator. It then analyzes this oscillation, looking for frequency changes which indicate energy errors. One can then compensate for or correct these energy errors. 6 refs., 1 fig

  9. Experimental results of the betatron sum resonance

    International Nuclear Information System (INIS)

    Wang, Y.; Ball, M.; Brabson, B.

    1993-06-01

    The experimental observations of motion near the betatron sum resonance, ν x + 2ν z = 13, are presented. A fast quadrupole (Panofsky-style ferrite picture-frame magnet with a pulsed power supplier) producing a betatron tune shift of the order of 0.03 at rise time of 1 μs was used. This quadrupole was used to produce betatron tunes which jumped past and then crossed back through a betatron sum resonance line. The beam response as function of initial betatron amplitudes were recorded turn by turn. The correlated growth of the action variables, J x and J z , was observed. The phase space plots in the resonance frame reveal the features of particle motion near the nonlinear sum resonance region

  10. Dispersion and betatron function correction in the Advanced Photon Source storage ring using singular value decomposition

    International Nuclear Information System (INIS)

    Emery, L.

    1999-01-01

    Magnet errors and off-center orbits through sextuples perturb the dispersion and beta functions in a storage ring (SR), which affects machine performance. In a large ring such as the Advanced Photon Source (APS), the magnet errors are difficult to determine with beam-based methods. Also the non-zero orbit through sextuples result from user requests for steering at light source points. For expediency, a singular value decomposition (SVD) matrix method analogous to orbit correction was adopted to make global corrections to these functions using strengths of several quadrupoles as correcting elements. The direct response matrix is calculated from the model of the perfect lattice. The inverse is calculated by SVD with a selected number of singular vectors. Resulting improvement in the lattice functions and machine performance will be presented

  11. Betatrons with kiloampere beams

    International Nuclear Information System (INIS)

    Peterson, J.M.

    1982-11-01

    Although the magnetic-induction method of acceleration used in the betatron is inherently capable of accelerating intense particle beams to high energy, many beam-instability questions arise when beams in the kilo-ampere range are considered. The intense electromagnetic fields produced by the beam, and by the image currents and charges induced in the surrounding walls, can produce very disruptive effects. Several unstable modes of collective oscillation are possible; the suppression of any one of them usually involves energy spread for Landau damping and careful design of the electrical character of the vacuum chamber. The various design criteria are often mutually incompatible. Space-charge detuning can be severe unless large beam apertures and high-energy injection are used. In order to have an acceptably low degree of space-charge detuning in the acceleration of a 10-kilo-ampere electron beam, for example, an injection energy on the order of 50 MeV seems necessary, in which case the forces due to nearby wall images can have a larger effect than the internal forces of the beam. A method of image compensation was invented for reducing the net image forces; it serves also to decrease the longitudinal beam impedance and thus helps alleviate the longitudinal instability as well. In order to avoid the ion-electron collective instability a vacuum in the range of 10 - 8 torr is required for an acceleration time of 1 millisecond. A multi-ring betatron system using the 50-MeV Advanced Test Accelerator at LLNL as an injector was conceptually designed

  12. Betatron tune measurement

    International Nuclear Information System (INIS)

    Dinev, D.

    2001-01-01

    On the basis of the comparative review of the methods for the betatron tune measurement in cyclic accelerators of synchrotrons type, the research of these methods is carried out from the point of view of their applicability to Nuclotron. Both methods using measurement of the statistical fluctuations of the beam current (Schottky noise) and methods using coherent beam excitation have been discussed. The emphasis is on the final results of importance for the tune measurement practice. Signal processing is briefly discussed too

  13. Phase advance and β function measurements using model-independent analysis

    OpenAIRE

    Chun-xi Wang; Vadim Sajaev; Chih-Yuan Yao

    2003-01-01

    Phase advance and β function are basic lattice functions characterizing the linear properties of an accelerator lattice. Accurate and efficient measurements of these quantities are important for commissioning and operating a machine. For rings with little coupling, we report a new method to measure these lattice functions based on the model-independent analysis technique, which uses beam histories of excited betatron oscillations measured simultaneously at a large number of beam position moni...

  14. High current betatron research at the University of New Mexico

    International Nuclear Information System (INIS)

    Humphries, S. Jr.; Len, L.K.

    1987-01-01

    Betatrons are among the simplest of high energy accelerators. Their circuit is equivalent to a step-up transformer; the electron beam forms a multi-turn secondary winding. Circulation of the beam around the flux core allows generation of high energy electrons with relatively small core mass. As with any transformer, a betatron is energy inefficient at low beam current; the energy balance is dominated by core losses. This fact has prompted a continuing investigation of high current betatrons as efficient, compact sources of beta and gamma radiation. A program has been supported at the University of New Mexico by the Office of Naval Research to study the physics of high current electron beams in circular accelerators and to develop practical technology for high power betatrons. Fabrication and assembly of the main ring was completed in January of this year. In contrast to other recent high current betatron experiments the UNM device utilizes a periodic focusing system to contain high current beams during the low energy phase of the acceleration cycle. The reversing cusp fields generated by alternating polarity solenoidal lenses cancel beam drift motions induced by machine errors. In consequence, they have found that the cusp geometry has had significantly better stability properties than a monodirectional toroidal field. In comparison to other minimum-Β geometries such as the Stelllatron cusps have open field lines which facilitate beam injection and neutralization

  15. Modified betatron for ion beam fusion

    International Nuclear Information System (INIS)

    Rostoker, N.; Fisher, A.

    1986-01-01

    An intense neutralized ion beam can be injected and trapped in magnetic mirror or tokamak geometry. The details of the process involve beam polarization so that the beam crosses the fringing fields without deflection and draining the polarization when the beam reaches the plasma. Equilibrium requires that a large betatron field be added in tokamak geometry. In mirror geometry a toroidal field must be added by means of a current along the mirror axis. In either case, the geometry becomes that of the modified betatron which has been studied experimentally and theoretically in recent years. We consider beams of d and t ions with a mean energy of 500 kev and a temperature of about 50 kev. The plasma may be a proton plasma with cold ions. It is only necessary for beam trapping or to carry currents. The ion energy for slowing down is initially 500 kev and thermonuclear reactions depend only on the beam temperature of 50 kev which changes very slowly. This new configuration for magnetic confinement fusion leads to an energy gain of 10--20 for d-t reactions whereas previous studies of beam target interaction predicted a maximum energy gain of 3--4. The high beam energy available with pulsed ion diode technology is also essential for advanced fuels. 16 refs., 3 figs

  16. Algorithms for a Precise Determination of the Betatron Tune

    CERN Document Server

    Bartolini, R; Giovannozzi, Massimo; Todesco, Ezio; Scandale, Walter

    1996-01-01

    In circular accelerators the precise knowledge of the betatron tune is of paramount importance both for routine operation and for theoretical investigations. The tune is measured by sampling the transverse position of the beam for N turns and by performing the FFT of the stored data. One can also evaluate it by computing the Average Phase Advance (APA) over N turns. These approaches have an intrinsic error proportional to 1/N. However, there are special cases where either a better precision or a faster measurement is desired. More efficient algorithms can be used, as those suggested by E.Asseo [1] and recently by J. Laskar [2]. They provide tune estimates by far more precise than those of a plain FFT, as discussed in Ref. [3]. Another important isssue is the effect of the finite resolution of the instrumentation used to measure the beam position. This introduces a noise and the frequency response of the beam is modified [4,5} thus reducing the precision by which the tune is determined. In Section 2 we recall ...

  17. Betatron tune correction schemes in nuclotron

    International Nuclear Information System (INIS)

    Shchepunov, V.A.

    1992-01-01

    Algorithms of the betatron tune corrections in Nuclotron with sextupolar and octupolar magnets are considered. Second order effects caused by chromaticity correctors are taken into account and sextupolar compensation schemes are proposed to suppress them. 6 refs.; 1 tab

  18. Synchro-betatron resonances driven by the beam-beam interaction

    International Nuclear Information System (INIS)

    Furman, M.A.

    1994-01-01

    We present a selective summary of the discussions on beam-beam-driven synchrobetatron resonances at the 6th Advanced ICFA Beam Dynamics Workshop on the subject ''Synchro-Betatron Resonances,'' held in Funchal (Madeira, Portugal), October 24--30, 1993

  19. Synchro-betatron resonance excitation in LEP

    International Nuclear Information System (INIS)

    Myers, S.

    1987-01-01

    The excitation of synchrotro-betatron resonances due to spurious dispersion and induced transverse deflecting fields at the RF cavities has been simulated for the LEP storage ring. These simulations have been performed for various possible modes of operation. In particular, a scenario has been studied in which LEP is operated at the maximum possible value of the synchrotron tune throughout the acceleration cycle, in an attempt to maximise the threshold intensity at which the Transverse Mode Coupling Instability (TMCI) occurs. This mode of operation necessitates the crossing of synchro-betatron resonances at some points in the acceleration cycle if low order non-linear machine resonances are to be avoided. Simulations have been performed in which the machine tune is swept across these synchro-betratron resonances at a rate given by the bandwidth of the magnet plus power supply circuits of the main quadrupole chain. The effect of longitudinal and transverse wake-fields on the excitation of these resonances has been investigated. These studies indicate that the distortion of the RF potential well caused by the longitudinal wake fields increases the non-linear content of the synchrotron motion and consequently increases significantly the excitation of the higher order synchro-betatron resonances

  20. Betatron activation analysis of cupriferous flotation pulp

    International Nuclear Information System (INIS)

    Kaminski, R.; Matenko, J.; Mencel, J.; Janiczek, J.; Kielsznia, J.

    1974-01-01

    A method of copper determination in cupriferous flotation pulp by photo-activation analysis using betatron and another equipments of existent ''analytical line'' intended for copper determination in dry samples has been described. An activation has been achieved with 14.9 MeV γ-photons. The excitation activity was investigated by using two scintillation detectors and a fast coincidence circuit with resolution time 80 ns. The precision of method was determined as +- 4.25% in 0.95 confidence level for pulp with concentration 5% Cu and +- 24% for 0.06% Cu. (author)

  1. PRINCIPLE OF SKEW QUADRUPOLE MODULATION TO MEASURE BETATRON COUPLING

    International Nuclear Information System (INIS)

    LUO, Y.; PILAT, F.; ROSER, T.

    2004-01-01

    The measurement of the residual betatron coupling via skew quadrupole modulation is a new diagnostics technique that has been developed and tested at the Relativistic Heavy Ion Collider (RHIC) as a very promising method for the linear decoupling on the ramp. By modulating the strengths of different skew quadrupole families the two eigentunes are precisely measured with the phase lock loop system. The projections of the residual coupling coefficient onto the skew quadrupole coupling modulation directions are determined. The residual linear coupling could be corrected according to the measurement. An analytical solution for skew quadrupole modulation based on Hamiltonian perturbation approximation is given, and simulation code using smooth accelerator model is also developed. Some issues concerning the practical applications of this technique are discussed

  2. Synchro-betatron resonance due to gap voltage asymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Baartman, R

    1992-11-01

    RF cavities for synchrotrons are not in general axially symmetric. This can be due, for example, to the location of the input power coupling loop. It can cause the voltage on one side of the accelerating gap to be different from that on the other side. Associated with this asymmetry is an rf magnetic field which deflects a beam particle by an amount depending upon its rf phase. The deflection can accumulate if the betatron tune is situated on a synchrotron sideband of the integer resonance. We develop the theory for this resonance and apply it to the KAON Factory Booster and to the SSC LEB. We find that the upper limit on allowable voltage asymmetry across the beam pipe is 0.1% in both cases. (author) 5 refs., 1 tab.

  3. Improved control of the betatron coupling in the Large Hadron Collider

    Science.gov (United States)

    Persson, T.; Tomás, R.

    2014-05-01

    The control of the betatron coupling is of importance for safe beam operation in the LHC. In this article we show recent advancements in methods and algorithms to measure and correct coupling. The benefit of using a more precise formula relating the resonance driving term f1001 to the ΔQmin is presented. The quality of the coupling measurements is increased, with about a factor 3, by selecting beam position monitor (BPM) pairs with phase advances close to π/2 and through data cleaning using singular value decomposition with an optimal number of singular values. These improvements are beneficial for the implemented automatic coupling correction, which is based on injection oscillations, presented in the article. Furthermore, a proposed coupling feedback for the LHC is presented. The system will rely on the measurements from BPMs equipped with a new type of high resolution electronics, diode orbit and oscillation, which will be operational when the LHC restarts in 2015. The feedback will combine the coupling measurements from the available BPMs in order to calculate the best correction.

  4. Improved control of the betatron coupling in the Large Hadron Collider

    Directory of Open Access Journals (Sweden)

    T. Persson

    2014-05-01

    Full Text Available The control of the betatron coupling is of importance for safe beam operation in the LHC. In this article we show recent advancements in methods and algorithms to measure and correct coupling. The benefit of using a more precise formula relating the resonance driving term f_{1001} to the ΔQ_{min} is presented. The quality of the coupling measurements is increased, with about a factor 3, by selecting beam position monitor (BPM pairs with phase advances close to π/2 and through data cleaning using singular value decomposition with an optimal number of singular values. These improvements are beneficial for the implemented automatic coupling correction, which is based on injection oscillations, presented in the article. Furthermore, a proposed coupling feedback for the LHC is presented. The system will rely on the measurements from BPMs equipped with a new type of high resolution electronics, diode orbit and oscillation, which will be operational when the LHC restarts in 2015. The feedback will combine the coupling measurements from the available BPMs in order to calculate the best correction.

  5. Dispersion and betatron matching into the linac

    International Nuclear Information System (INIS)

    Decker, F.J.; Adolphsen, C.; Corbett, W.J.; Emma, P.; Hsu, I.; Moshammer, H.; Seeman, J.T.; Spence, W.L.

    1991-05-01

    In high energy linear colliders, the low emittance beam from a damping ring has to be preserved all the way to the linac, in the linac and to the interaction point. In particular, the Ring-To-Linac (RTL) section of the SLAC Linear Collider (SLC) should provide an exact betatron and dispersion match from the damping ring to the linac. A beam with a non-zero dispersion shows up immediately as an increased emittance, while with a betatron mismatch the beam filaments in the linac. Experimental tests and tuning procedures have shown that the linearized beta matching algorithms are insufficient if the actual transport line has some unknown errors not included in the model. Also, adjusting quadrupole strengths steers the beam if it is offset in the quadrupole magnets. These and other effects have lead to a lengthy tuning process, which in the end improves the matching, but is not optimal. Different ideas will be discussed which should improve this matching procedure and make it a more reliable, faster and simpler process. 5 refs., 2 figs

  6. Advanced Athermal Telescopes, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposed innovative athermal telescope design uses advanced lightweight and high-stiffness material of Beryllium-Aluminum (Be-38Al). Peregrine's expertise with...

  7. Betatron coupling: Merging Hamiltonian and matrix approaches

    Directory of Open Access Journals (Sweden)

    R. Calaga

    2005-03-01

    Full Text Available Betatron coupling is usually analyzed using either matrix formalism or Hamiltonian perturbation theory. The latter is less exact but provides a better physical insight. In this paper direct relations are derived between the two formalisms. This makes it possible to interpret the matrix approach in terms of resonances, as well as use results of both formalisms indistinctly. An approach to measure the complete coupling matrix and its determinant from turn-by-turn data is presented. Simulations using methodical accelerator design MAD-X, an accelerator design and tracking program, were performed to validate the relations and understand the scope of their application to real accelerators such as the Relativistic Heavy Ion Collider.

  8. Advances phase-lock techniques

    CERN Document Server

    Crawford, James A

    2008-01-01

    From cellphones to micrprocessors, to GPS navigation, phase-lock techniques are utilized in most all modern electronic devices. This high-level book takes a systems-level perspective, rather than circuit-level, which differentiates it from other books in the field.

  9. Application of betatrons to quality control of structures

    International Nuclear Information System (INIS)

    Klevtsov, V.A.; Matveev, Yu.K.; Trefilov, V.V.

    1986-01-01

    The results of laboratory investigations on the applicability of modificated PMB-6 betatron to quality control of reinforced concrete structures are presented. The investigations have been performed for the purposes of refinement of the technique for detecting voids and establishing real reinforcement. On the basis of experimental investigations the technique and schemes of structure translucence have been developed. Examples of using betatrons for flaw detection of reinforred concrete structures are given

  10. Application of a Betatron in Photonuclear Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brune, D [AB Atomenergi, Nykoeping (Sweden); Mattsson, K; Liden, K [Dept . of Radiation Physics, Univ. of Lund (Sweden)

    1968-08-15

    The present study concerns the determination of fluorine, iodine, lead and mercury by means of photonuclear activation technique using a betatron. The detection limit obtained for the elements in the above given sequence amounted to 3, 50, 400 and 15 {mu}g respectively. The technique has been applied in the determination of iodine in pharmaceuticals. A rotating sample holder device was inserted in the Bremsstrahlung beam of the betatron in order to ensure uniform irradiation of the samples.

  11. Advanced Gouy phase high harmonics interferometer

    Science.gov (United States)

    Mustary, M. H.; Laban, D. E.; Wood, J. B. O.; Palmer, A. J.; Holdsworth, J.; Litvinyuk, I. V.; Sang, R. T.

    2018-05-01

    We describe an extreme ultraviolet (XUV) interferometric technique that can resolve ∼100 zeptoseconds (10‑21 s) delay between high harmonic emissions from two successive sources separated spatially along the laser propagation in a single Gaussian beam focus. Several improvements on our earlier work have been implemented in the advanced interferometer. In this paper, we report on the design, characterization and optimization of the advanced Gouy phase interferometer. Temporal coherence for both atomic argon and molecular hydrogen gases has been observed for several harmonic orders. It has been shown that phase shift of XUV pulses mainly originates from the emission time delay due to the Gouy phase in the laser focus and the observed interference is independent of the generating medium. This interferometer can be a useful tool for measuring the relative phase shift between any two gas species and for studying ultrafast dynamics of their electronic and nuclear motion.

  12. Coherent betatron instability in the Tevatron

    International Nuclear Information System (INIS)

    Bogacz, S.A.; Harrison, M.; Ng, K.Y.

    1988-01-01

    The coherent betatron instability was first observed during the recent 1987-88 Tevatron fixed target run. In this operating mode 1000 consecutive bunches are loaded into the machine at 150 GeV with a bunch spacing of 18.8 /times/ 10 -9 sec (53 MHz). The normalized transverse emittance is typically 15 π /times/ 10 -6 m rad in each plane with a longitudinal emittance of about 1.5 eV-sec. The beam is accelerated to 800 GeV in 13 sec. and then it is resonantly extracted during a 23 sec flat top. As the run progressed the bunch intensities were increased until at about 1.4 /times/ 10 10 ppb (protons per bunch) we experienced the onset of a coherent horizontal oscillation taking place in the later stages of the acceleration cycle (>600 GeV). This rapidly developing coherent instability results in a significant emittance growth, which limits machine performance and in a catastrophic scenario it even prevents extraction of the beam. In this paper we will present a simple analytic description of the observed instability. We will show that a combination of a resistive wall coupled bunch effect and a single bunch slow head-tail instability is consistent with the above observations. Finally, a systematic numerical analysis of our model (growth-time vs chromaticity plots) points to the existence of the ≥1 slow head-tail modes as a plausible mechanism for the observed coherent instability. This last claim, as mentioned before, does not have conclusive experimental evidence, although it is based on a very good agreement between the measured values of the instability growth-time and the ones calculated on the basis of our model. 4 refs., 3 figs

  13. Computational advances in transition phase analysis

    International Nuclear Information System (INIS)

    Morita, K.; Kondo, S.; Tobita, Y.; Shirakawa, N.; Brear, D.J.; Fischer, E.A.

    1994-01-01

    In this paper, historical perspective and recent advances are reviewed on computational technologies to evaluate a transition phase of core disruptive accidents in liquid-metal fast reactors. An analysis of the transition phase requires treatment of multi-phase multi-component thermohydraulics coupled with space- and energy-dependent neutron kinetics. Such a comprehensive modeling effort was initiated when the program of SIMMER-series computer code development was initiated in the late 1970s in the USA. Successful application of the latest SIMMER-II in USA, western Europe and Japan have proved its effectiveness, but, at the same time, several areas that require further research have been identified. Based on the experience and lessons learned during the SIMMER-II application through 1980s, a new project of SIMMER-III development is underway at the Power Reactor and Nuclear Fuel Development Corporation (PNC), Japan. The models and methods of SIMMER-III are briefly described with emphasis on recent advances in multi-phase multi-component fluid dynamics technologies and their expected implication on a future reliable transition phase analysis. (author)

  14. Formation of Field-reversed-Configuration Plasma with Punctuated-betatron-orbit Electrons

    International Nuclear Information System (INIS)

    Welch, D.R.; Cohen, S.A.; Genoni, T.C.; Glasser, A.H.

    2010-01-01

    We describe ab initio, self-consistent, 3D, fully electromagnetic numerical simulations of current drive and field-reversed-configuration plasma formation by odd-parity rotating magnetic fields (RMFo). Magnetic-separatrix formation and field reversal are attained from an initial mirror configuration. A population of punctuated-betatron-orbit electrons, generated by the RMFo, carries the majority of the field-normal azimuthal electrical current responsible for field reversal. Appreciable current and plasma pressure exist outside the magnetic separatrix whose shape is modulated by the RMFo phase. The predicted plasma density and electron energy distribution compare favorably with RMFo experiments.

  15. Phase camera experiment for Advanced Virgo

    Energy Technology Data Exchange (ETDEWEB)

    Agatsuma, Kazuhiro, E-mail: agatsuma@nikhef.nl [National Institute for Subatomic Physics, Amsterdam (Netherlands); Beuzekom, Martin van; Schaaf, Laura van der [National Institute for Subatomic Physics, Amsterdam (Netherlands); Brand, Jo van den [National Institute for Subatomic Physics, Amsterdam (Netherlands); VU University, Amsterdam (Netherlands)

    2016-07-11

    We report on a study of the phase camera, which is a frequency selective wave-front sensor of a laser beam. This sensor is utilized for monitoring sidebands produced by phase modulations in a gravitational wave (GW) detector. Regarding the operation of the GW detectors, the laser modulation/demodulation method is used to measure mirror displacements and used for the position controls. This plays a significant role because the quality of controls affect the noise level of the GW detector. The phase camera is able to monitor each sideband separately, which has a great benefit for the manipulation of the delicate controls. Also, overcoming mirror aberrations will be an essential part of Advanced Virgo (AdV), which is a GW detector close to Pisa. Especially low-frequency sidebands can be affected greatly by aberrations in one of the interferometer cavities. The phase cameras allow tracking such changes because the state of the sidebands gives information on mirror aberrations. A prototype of the phase camera has been developed and is currently tested. The performance checks are almost completed and the installation of the optics at the AdV site has started. After the installation and commissioning, the phase camera will be combined to a thermal compensation system that consists of CO{sub 2} lasers and compensation plates. In this paper, we focus on the prototype and show some limitations from the scanner performance. - Highlights: • The phase camera is being developed for a gravitational wave detector. • A scanner performance limits the operation speed and layout design of the system. • An operation range was found by measuring the frequency response of the scanner.

  16. Phase camera experiment for Advanced Virgo

    International Nuclear Information System (INIS)

    Agatsuma, Kazuhiro; Beuzekom, Martin van; Schaaf, Laura van der; Brand, Jo van den

    2016-01-01

    We report on a study of the phase camera, which is a frequency selective wave-front sensor of a laser beam. This sensor is utilized for monitoring sidebands produced by phase modulations in a gravitational wave (GW) detector. Regarding the operation of the GW detectors, the laser modulation/demodulation method is used to measure mirror displacements and used for the position controls. This plays a significant role because the quality of controls affect the noise level of the GW detector. The phase camera is able to monitor each sideband separately, which has a great benefit for the manipulation of the delicate controls. Also, overcoming mirror aberrations will be an essential part of Advanced Virgo (AdV), which is a GW detector close to Pisa. Especially low-frequency sidebands can be affected greatly by aberrations in one of the interferometer cavities. The phase cameras allow tracking such changes because the state of the sidebands gives information on mirror aberrations. A prototype of the phase camera has been developed and is currently tested. The performance checks are almost completed and the installation of the optics at the AdV site has started. After the installation and commissioning, the phase camera will be combined to a thermal compensation system that consists of CO 2 lasers and compensation plates. In this paper, we focus on the prototype and show some limitations from the scanner performance. - Highlights: • The phase camera is being developed for a gravitational wave detector. • A scanner performance limits the operation speed and layout design of the system. • An operation range was found by measuring the frequency response of the scanner.

  17. Evaluation of the combined betatron and momentum cleaning in point 3 in terms of cleaning efficiency and energy deposition for the LHC Collimation upgrade

    CERN Document Server

    Lari, L; Boccone, V; Brugger, M; Cerutti, F; Ferrari, A; Rossi, A; Versaci, R; Vlachoudis, V; Wollmann, D; Mereghetti, A; Faus-Golfe, A

    2011-01-01

    The Phase I LHC Collimation System Upgrade could include moving part of the Betatron Cleaning from LHC Point 7 to Point 3 to improve both operation flexibility and intensity reach. In addition, the partial relocation of beam losses from the current Betatron cleaning region at Point 7 will mitigate the risks of Single Event Upsets to equipment installed in adjacent and partly not sufficient shielded areas. The combined Betatron and Momentum Cleaning at Point 3 implies that new collimators have to be added as well as to implement a new collimator aperture layout. This paper shows the whole LHC Collimator Efficiency variation with the new layout at different beam energies. As part of the evaluation, energy deposition distribution in the IR3 region give indications about the effect of this new implementations not only on the collimators themselves but also on the other beam line elements as well as in the IR3 surrounding areas.

  18. Betatron radiation from a laser-plasma accelerator

    International Nuclear Information System (INIS)

    Schnell, Michael

    2014-01-01

    The presented thesis investigates the processes which lead to the generation of highenergetic X-ray radiation, also known as ''betatron radiation'', by means of a relativistic laser-plasma interaction. The generated betatron radiation has been extensively characterized by measuring its radiated intensity, energy distribution, far-field beam profile, and source size. It was shown for the first time that betatron radiation can be used as a non-invasive diagnostic tool to retrieve very subtle information on the electron acceleration dynamics within the plasma wave. Furthermore, a compact polarimeter setup has been developed in a unique experiment in which the polarization state of the laser-plasma generated betatron radiation was measured in single-shot mode. This lead to a detailed study of the orientation of the electron trajectory within the plasma interaction. By controlling the injection of the electrons into the plasma wave it was demonstrated that one can tune the polarization state of the emitted X-rays. This result is very promising for further applications, particularly for feeding the electrons into an additional conventional accelerator or a permanent magnet based undulator for the production of intense X-ray beams. During this work, the experimental setup for accelerating electrons and generating high-energy X-ray beams was consistently improved: to enhance both its reliability and stability. Subsequently, the betatron radiation was used as a reliable diagnostic tool of the electron dynamics within the plasma. Parallel to the experimental work, 3-Dimensional Particle-In-Cell (3D-PlC) simulations were performed together with colleagues from the University of Duesseldorf. The simulations included the electron acceleration and the X-ray generation processes together with the recoil force acting on an accelerating electron caused by the emitted radiation during which one can also ascertain its polarization state. The simulations proved to be in good agreement

  19. Inductive-pulsed power supplying system for a betatron electromagnet

    International Nuclear Information System (INIS)

    Otrubyannikov, Yu.A.; Safronov, A.S.

    1984-01-01

    Circuit of producing quasitriangular current pulses designed for the pulsed power supply system of betatron electromagnet is described. Introduction of additional winding into electromagnet provides circuit galvanic isolation, artificial commutation of basic circuit thyristors and inductive power input to the winding during thyristor commutation. The considered system is used for excitation of betatron electromagnet up to 18 MeV. Magnetic field energy equals 1100 Y. The maximal voltage in energy storage capacitor - 4.8 kV. Current amplitude in basic winding - 335 A. The number of loops in basic winding equals 80, in additional one - 32. Current pulse duration in electromagnet-3.8 ms. The system provides operation with controlled current pulse frequency from 0 up to 150 Hz. The maximal consumption power - 18 kW

  20. Linear theory of beam depolarization due to vertical betatron motion

    International Nuclear Information System (INIS)

    Chao, A.W.; Schwitters, R.F.

    1976-06-01

    It is well known that vertical betatron motion in the presence of quantum fluctuations leads to some degree of depolarization of a transversely polarized beam in electron-positron storage rings even for energies away from spin resonances. Analytic formulations of this problem, which require the use of simplifying assumptions, generally have shown that there exist operating energies where typical storage rings should exhibit significant beam polarization. Due to the importance of beam polarization in many experiments, we present here a complete calculation of the depolarization rate to lowest order in the perturbing fields, which are taken to be linear functions of the betatron motion about the equilibrium orbit. The results are applicable to most high energy storage rings. Explicit calculations are given for SPEAR and PEP. 7 refs., 8 figs

  1. Betatron stochastic cooling in the Debuncher: Present and future

    International Nuclear Information System (INIS)

    Visnjic, V.

    1993-07-01

    A detailed study of the betatron stochastic cooling in the Debuncher is presented. First, a complete theoretical model including the emittance-dependent signal-to-noise ratio as well as time-dependent mixing is constructed. The emittance measurements in the Debuncher are described and it is shown that the model is in excellent agreement with the experimental data. The idea of gain shaping is proposed and it is shown that the gain shaping would improve the cooling of the beam. Several proposals for future improvements are studied and appraised, in particular, gain shaping, ramped η, and cryogenic and ''smart'' pickups and kickers. Finally, the demands which the Main Injector will impose on the Debuncher are analyzed and a design of the betatron stochastic cooling system for the Main Injector era is outlined

  2. Long-wavelength negative mass instabilities in high current betatrons

    International Nuclear Information System (INIS)

    Godfrey, B.B.; Hughes, T.P.

    1985-01-01

    Growth rates of negative mass instabilities in conventional and modified betatrons are calculated by analytic methods and by performing three-dimensional particle simulations. In contrast to earlier work, toroidal corrections to the field equations are included in the analytic model. As a result, good agreement with numerical simulations is obtained. The simulations show that the nonlinear development of the instabilities can seriously disrupt the beam

  3. Advanced Situation Awareness Technologies, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Situation Awareness Technologies (ASAT) will facilitate exploration of the moon surface, and other planetary bodies. ASAT will create an Advanced Situation...

  4. Investigation of betatron instability in a wiggler pumped ion-channel free electron laser

    Energy Technology Data Exchange (ETDEWEB)

    Raghavi, A [Physics Department, Payame Noor University, 19395-4697 (Iran, Islamic Republic of); Mehdian, H, E-mail: Raghavi@tmu.ac.ir, E-mail: Mehdian@tmu.ac.ir [Department of Physics, Teacher Training University, Tehran (Iran, Islamic Republic of)

    2011-10-15

    Betatron emission from an ion-channel free electron laser in the presence of a helical wiggler pump and in the high gain regime is studied. The dispersion relation and the frequency of betatron emission are derived. Growth rate is illustrated and maximum growth rate as a function of ion-channel density is considered. Finally, the relation between beam energy, the density of ion channel and the region of betatron emission is discussed.

  5. Measurement of betatron-tune in the KEK 12 GeV-PS/J-PARC

    International Nuclear Information System (INIS)

    Miura, Takako; Toyama, Takeshi; Igarashi, Susumu; Hayashi, Naoki

    2004-01-01

    Measurement of betatron-tune in the KEK 12 GeV-PS is performed by using band limited white noise which excites coherent betatron oscillations via stripline unit. We compared the results of the measurement for betatron oscillation amplitude with the result of calculation, and confirmed the consistency. The design of the tune-monitor in J-PARC was also discussed applying this result. (author)

  6. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Combinatorial methods are proposed to develop advanced Aqueous Oxidation Catalysts (AOCs) with the capability to mineralize organic contaminants present in effluents...

  7. Advanced Mars Water Acquisition System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Mars Water Acquisition System (AMWAS) recovers and purifies water from Mars soils for oxygen and fuel production, life support, food production, and...

  8. Advanced Carbothermal Electric Reactor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop the Advanced Carbothermal Electric (ACE) reactor to efficiently extract oxygen from lunar regolith. Unlike state-of-the-art carbothermal...

  9. Advanced TCCS for Spacesuit Applications, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A recent trade study showed that active removal of ammonia (NH3) and formaldehyde (CH2O) is crticial to meeting the 24-hr SMAC limits in the advanced space suit...

  10. Advanced Green Micropropulsion System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Systima in collaboration with University of Washington is developing a high performance injection system for advanced green monopropellant AF-M315E micropropulsion...

  11. Advanced Green Micropropulsion System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Systima in collaboration with the University of Washington will develop a high performance, advanced green monopropellant microthruster (0.1 – 1.0 N) for small- and...

  12. Advanced supersonic propulsion study, phase 3

    Science.gov (United States)

    Howlett, R. A.; Johnson, J.; Sabatella, J.; Sewall, T.

    1976-01-01

    The variable stream control engine is determined to be the most promising propulsion system concept for advanced supersonic cruise aircraft. This concept uses variable geometry components and a unique throttle schedule for independent control of two flow streams to provide low jet noise at takeoff and high performance at both subsonic and supersonic cruise. The advanced technology offers a 25% improvement in airplane range and an 8 decibel reduction in takeoff noise, relative to first generation supersonic turbojet engines.

  13. Optimization of the Phase Advance Between RHIC Interaction Points

    CERN Document Server

    Tomas, Rogelio

    2005-01-01

    We consider the scenario of having two identical Interaction Points (IPs) in the Relativistic Heavy Ion Collider (RHIC). The strengths of beam-beam resonances strongly depend on the phase advance between these two IPs and therefore certain phase advances could improve beam lifetime and luminosity. We compute the dynamic aperture as function of the phase advance between these IPs to find the optimum settings. The beam-beam interaction is treated in the weak-strong approximation and a complete non-linear model of the lattice is used. For the current RHIC proton working point (0.69,0.685) the design lattice is found to have the optimum phase advance. However this is not the case for other working points.

  14. Traveling wave accelerating structures with a large phase advance

    International Nuclear Information System (INIS)

    Paramonov, V.V.

    2012-01-01

    The cells RF parameters for the well known Disk Loaded Waveguide (DLW) are considered in higher pass bands of TM01 wave, providing operating phase advance between 180 o - 1230 o per cell. With an appropriate shape optimization and some additional elements proposed traveling wave structures with such large phase advance overlap the classical first band DLW in RF efficiency. Examples of proposed structures together with RF and dispersion properties are presented.

  15. Advanced Gearless Drivetrain - Phase I Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Butterfield, Sandy; Smith, Jim; Petch, Derek; Sullivan, Brian; Smith, Peter; Pierce, Kirk

    2012-08-31

    Boulder Wind Power (BWP) collaborated with the National Renewable Energy Laboratory (NREL) in Golden, Colorado, to demonstrate the economics of scaling an advanced gearless drivetrain technology to 6MW (and larger) turbine applications. The project goal was to show that this advanced drivetrain technology enables a cost of energy of less than $0.10/kWH in offshore applications. This drivetrain technology achieves this Cost of Energy (COE) advantage via a 70% greater torque density versus current state-of-the-art drivetrain technologies. In addition, a new dynamically compliant design strategy is required to optimize turbine system-level COE. The BWP generator is uniquely suited for this new design strategy. This project developed a concept design for a 6MW drivetrain and culminated in a plan for a system-level test of this technology at 3MW scale. The project further demonstrated the advantage of the BWP drivetrain with increasing power ratings, with conceptual designs through 10 MW.

  16. Bruno Touschek: From Betatrons to Electron-Positron Colliders

    Science.gov (United States)

    Bernardini, Carlo; Pancheri, Giulia; Pellegrini, Claudio

    Bruno Touschek’s life as a physicist spanned the period from World War II to the 1970s. He was a key figure in the developments of electron-positron colliders and storage rings, and made important contributions to theoretical high energy physics. Storage rings, initially developed for high energy physics, are being widely used in many countries as synchrotron radiation sources and are a tool for research in physics, chemistry, biology, environmental sciences and cultural heritage studies. We describe Touschek’s life in Austria, where he was born, in Germany, where he participated in the construction of a betatron during WWII, and in Italy, where he proposed and led to completion the first electron-positron storage ring in 1960, in Frascati. We highlight how his central European culture influenced his lifestyle and work, and his main contributions to physics, such as the discovery of the Touschek effect and beam instabilities in the larger storage ring ADONE.

  17. Fast betatron tune controller for circulating beam in a synchrotron

    International Nuclear Information System (INIS)

    Endo, Takuyuki; Hatanaka, Kichiji; Sato, Kenji

    1997-01-01

    When rf quadrupole (RFQ) electric field is applied to the circulating beam in a synchrotron, an equation of motion is reduced to Mathieu's Equation. A new analytical method to obtain an approximate solution has been developed, while a numerical computation was usually applied. Translating the behavior of approximate solution into terms of an RFQ electric field and betatron oscillation, a fast tune control can be achieved by rapid tuning of both amplitude and frequency of rf voltage. This process could be applied to suppress a tune shift caused by a space charge effect and to control a slow beam extraction with a low ripple. We have started another analytical computation using Hamiltonian with perturbation of RFQ and the results of this computation also suggest that it is applicable to slow beam extraction. The fast tune controller has been constructed and the beam test will be performed at HIMAC synchrotron in cooperation of RCNP and NIRS. (author)

  18. Advanced supersonic propulsion study, phase 4

    Science.gov (United States)

    Howlett, R. A.

    1977-01-01

    Installation characteristics for a Variable Stream Control Engine (VSCE) were studied for three advanced supersonic airplane designs. Sensitivity of the VSCE concept to change in technology projections was evaluated in terms of impact on overall installed performance. Based on these sensitivity results, critical technology requirements were reviewed, resulting in the reaffirmation of the following requirements: low-noise nozzle system; a high performance, low emissions duct burner and main burner; hot section technology; variable geometry components; and propulsion integration features, including an integrated electronic control system.

  19. Dynamics Assessment of Advanced Single-Phase PLL Structures

    DEFF Research Database (Denmark)

    Golestan, Saeed; Monfarad, Mohammad; Freijedo, Francisco D.

    2013-01-01

    Recently, several advanced phase locked loop (PLL) techniques have been proposed for single-phase applications. Among these, the Park-PLL, and the second order generalized integrator (SOGI) based PLL are very attractive, owing to their simple digital implementation, low computational burden...

  20. Advanced frequency synthesis by phase lock

    CERN Document Server

    Egan, William F

    2011-01-01

    "An addendum to the popular Frequency Synthesis by Phase Lock, 2nd ed, this book describes sigma-delta, a frequency synthesis technique that has gained prominence in recent years. In addition, Simulink will be employed extensively to guide the reader. Fractional-n, the still-used forerunner to sigma-delta, is also discussed. Sequences of simulated results allow the reader to gain a deeper understanding while detailed appendices provide information from various stages of development. Simulation models discussed in the chapters that are available online."--Provided by publisher.

  1. Digital polarization holography advancing geometrical phase optics.

    Science.gov (United States)

    De Sio, Luciano; Roberts, David E; Liao, Zhi; Nersisyan, Sarik; Uskova, Olena; Wickboldt, Lloyd; Tabiryan, Nelson; Steeves, Diane M; Kimball, Brian R

    2016-08-08

    Geometrical phase or the fourth generation (4G) optics enables realization of optical components (lenses, prisms, gratings, spiral phase plates, etc.) by patterning the optical axis orientation in the plane of thin anisotropic films. Such components exhibit near 100% diffraction efficiency over a broadband of wavelengths. The films are obtained by coating liquid crystalline (LC) materials over substrates with patterned alignment conditions. Photo-anisotropic materials are used for producing desired alignment conditions at the substrate surface. We present and discuss here an opportunity of producing the widest variety of "free-form" 4G optical components with arbitrary spatial patterns of the optical anisotropy axis orientation with the aid of a digital spatial light polarization converter (DSLPC). The DSLPC is based on a reflective, high resolution spatial light modulator (SLM) combined with an "ad hoc" optical setup. The most attractive feature of the use of a DSLPC for photoalignment of nanometer thin photo-anisotropic coatings is that the orientation of the alignment layer, and therefore of the fabricated LC or LC polymer (LCP) components can be specified on a pixel-by-pixel basis with high spatial resolution. By varying the optical magnification or de-magnification the spatial resolution of the photoaligned layer can be adjusted to an optimum for each application. With a simple "click" it is possible to record different optical components as well as arbitrary patterns ranging from lenses to invisible labels and other transparent labels that reveal different images depending on the side from which they are viewed.

  2. Two pedigrees of familial advanced sleep phase syndrome in Japan.

    Science.gov (United States)

    Satoh, Kohtoku; Mishima, Kazuo; Inoue, Yuichi; Ebisawa, Takashi; Shimizu, Tetsuo

    2003-06-15

    To determine whether a known missense mutation (bp2106 A/G) in hPer2 (a human homolog of the Drosophila period gene) for familial advanced sleep phase syndrome in a Caucasian family is involved in Japanese familial advanced sleep phase syndrome pedigrees. We identified 2 new Japanese families with advanced sleep phase syndrome, and a systematic survey was carried out in 28 relatives of theses 2 families. A total of 9 affected subjects were identified. The affected members showed significantly strong morningness tendencies compared with the unaffected members in various circadian parameters including the Horne-Ostberg Morningness-Eveningness Questionnaire score (77.3 +/- 4.8 vs 57.5 +/- 7.6, p sleep-onset time (20:45 +/- 75 min vs 23:16 +/- 64 min, p DNA samples were obtained from 7 affected and 7 unaffected subjects. None of the tested subjects possessed the missense mutation (bp2106 A/G) in hPer2. Furthermore, there is no significant linkage between affected subjects with hPer2 region by 2-point mapping and by direct sequencing of 23 exons of hPer2. These findings support the notion of genetic heterogeneity of familial advanced sleep phase syndrome cases in humans. The search for more familial advanced sleep phase syndrome cases and for loci other than hPer2 are necessary to further examine the roles of circadian-related genes in genetically determined human circadian rhythm disorders.

  3. Iron-free betatrons - short radiation pulse generators for roentgenography of fast-going processes

    Energy Technology Data Exchange (ETDEWEB)

    Pavlovskij, A P; Zenkov, D I; Kuropatkin, Yu P; Mironenko, V D; Suvorov, V N [All-Russian Scientific Research Inst. of Experimental Physics, Sarov (Russian Federation)

    1997-12-31

    The possibilities of further increasing the current in high-current iron-free betatrons are studied. The efficiency of electron capture has been successfully increased by introducing local disturbances of the betatron magnetic field. At the optimum ratios of the disturbing and the betatron field, and at the optimum winding geometry as for the field disturbances and their attenuation rate, a multi-revolution electron capture has been achieved. The dependence of the circulating current on the injection energy was studied at the optimized facility with a porcelain accelerating chamber and a conducting cover. The experimental dependence is close to the calculated one. The maximum circulating current achieved was 28030 A which is the record value for circular accelerators. (J.U.). 1 tab., 5 figs., 2 refs.

  4. Chromaticity tracking using a phase modulation technique

    International Nuclear Information System (INIS)

    Tan, C.Y.; Fermilab

    2007-01-01

    In the classical chromaticity measurement technique, chromaticity is measured by measuring the change in betatron tune as the RF frequency is varied. This paper will describe a novel way of measuring chromaticity: we will phase modulate the RF with a known sine wave and then phase demodulate the betatron frequency. The result is a line in Fourier space which corresponds to the frequency of our sine wave modulation. The peak of this sine wave is proportional to chromaticity. For this technique to work, a tune tracker PLL system is required because it supplies the betatron carrier frequency. This method has been tested in the Tevatron and we will show the results here

  5. Tune shift and betatron modulations due to insertion devices in SPEAR

    International Nuclear Information System (INIS)

    Corbett, W.J.

    1989-12-01

    SPEAR will soon operate as a dedicated synchrotron radiation source with up to 5 beamlines fed from insertion devices. These magnets introduce additional focusing forces into the storage ring lattice which increase the vertical betatron tune and modulate the beam envelope in the vertical plane. The lattice simulation code 'GEMINI' is used to evaluate the tune shifts and estimate the degree of betatron modulation as each magnetic insertion device is brought up to full power. A program is recommended to correct the tunes with the FODO cell quadrupoles. 4 refs., 8 figs., 1 tab

  6. Betatron radiation based diagnostics for plasma wakefield accelerated electron beams at the SPARC-LAB test facility

    International Nuclear Information System (INIS)

    Shpakov, V.; Anania, M.P.; Biagioni, A.; Chiadroni, E.; Cianchi, A.; Curcio, A.; Dabagov, S.; Ferrario, M.; Filippi, F.; Marocchino, A.; Paroli, B.; Pompili, R.; Rossi, A.R.; Zigler, A.

    2016-01-01

    Recent progress with wake-field acceleration has shown a great potential in providing high gradient acceleration fields, while the quality of the beams remains relatively poor. Precise knowledge of the beam size at the exit from the plasma and matching conditions for the externally injected beams are the key for improvement of beam quality. Betatron radiation emitted by the beam during acceleration in the plasma is a powerful tool for the transverse beam size measurement, being also non-intercepting. In this work we report on the technical solutions chosen at SPARC-LAB for such diagnostics tool, along with expected parameters of betatron radiation. - Highlights: • The betatron radiation parameters in SPARC-LAB wakefiled experiments were studied. • The differences with betatron radiation in other wake-field experiments were highlighted. • The solution for betatron radiation detection was investigated.

  7. Betatron radiation based diagnostics for plasma wakefield accelerated electron beams at the SPARC-LAB test facility

    Energy Technology Data Exchange (ETDEWEB)

    Shpakov, V.; Anania, M.P.; Biagioni, A.; Chiadroni, E. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); Cianchi, A. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); “Tor Vergata” University, via della Ricerca Scientifica 1, 00133 Rome (Italy); Curcio, A. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); Dabagov, S. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); P.N. Lebedev Physical Institute RAS, Leninskiy Prospekt 53, 119991 Moscow (Russian Federation); NRNU “MEPhI”, Kashirskoe highway 31, 115409 Moscow (Russian Federation); Ferrario, M.; Filippi, F. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); Marocchino, A. [Dipartimento SBAI Universitá di Roma ‘La Sapienza’, via Antonio Scarpa 14/16, 00161 Rome (Italy); Paroli, B. [INFN - MI, via Celoria 16, 20133 Milan (Italy); Pompili, R. [INFN - LNF, via Enrico Fermi 40, 00044 Frascati (Italy); Rossi, A.R. [INFN - MI, via Celoria 16, 20133 Milan (Italy); Zigler, A. [Racah Institute of Physics Hebrew University of Jerusalem (Israel)

    2016-09-01

    Recent progress with wake-field acceleration has shown a great potential in providing high gradient acceleration fields, while the quality of the beams remains relatively poor. Precise knowledge of the beam size at the exit from the plasma and matching conditions for the externally injected beams are the key for improvement of beam quality. Betatron radiation emitted by the beam during acceleration in the plasma is a powerful tool for the transverse beam size measurement, being also non-intercepting. In this work we report on the technical solutions chosen at SPARC-LAB for such diagnostics tool, along with expected parameters of betatron radiation. - Highlights: • The betatron radiation parameters in SPARC-LAB wakefiled experiments were studied. • The differences with betatron radiation in other wake-field experiments were highlighted. • The solution for betatron radiation detection was investigated.

  8. Management of Advanced-Phase Chronic Myelogenous Leukemia.

    Science.gov (United States)

    Radich, Jerald P

    2016-05-01

    Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. Copyright © 2016 by the National Comprehensive Cancer Network.

  9. A normal form approach to the theory of nonlinear betatronic motion

    International Nuclear Information System (INIS)

    Bazzani, A.; Todesco, E.; Turchetti, G.; Servizi, G.

    1994-01-01

    The betatronic motion of a particle in a circular accelerator is analysed using the transfer map description of the magnetic lattice. In the linear case the transfer matrix approach is shown to be equivalent to the Courant-Snyder theory: In the normal coordinates' representation the transfer matrix is a pure rotation. When the nonlinear effects due to the multipolar components of the magnetic field are taken into account, a similar procedure is used: a nonlinear change of coordinates provides a normal form representation of the map, which exhibits explicit symmetry properties depending on the absence or presence of resonance relations among the linear tunes. The use of normal forms is illustrated in the simplest but significant model of a cell with a sextupolar nonlinearity which is described by the quadratic Henon map. After recalling the basic theoretical results in Hamiltonian dynamics, we show how the normal forms describe the different topological structures of phase space such as KAM tori, chains of islands and chaotic regions; a critical comparison with the usual perturbation theory for Hamilton equations is given. The normal form theory is applied to compute the tune shift and deformation of the orbits for the lattices of the SPS and LHC accelerators, and scaling laws are obtained. Finally, the correction procedure of the multipolar errors of the LHC, based on the analytic minimization of the tune shift computed via the normal forms, is described and the results for a model of the LHC are presented. This application, relevant for the lattice design, focuses on the advantages of normal forms with respect to tracking when parametric dependences have to be explored. (orig.)

  10. Therapy by stationary photon fields from a 42 MeV betatron using wedge filters

    International Nuclear Information System (INIS)

    Wicke, L.; Kaercher, K.H.; Naesiger, H.; Prokosch, E.; Vienna Univ.

    1975-01-01

    The dose distribution in photon beams from a 42 MeV betatron using wedge filters of lead with different angles of slope is described. The wedge coefficient to be considered at a field size of 10 x 10 cm is given. The scope for isodoses modified by wedge filters is discussed with regard to stationary-field photon therapy. (orig.) [de

  11. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    Directory of Open Access Journals (Sweden)

    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  12. Correction of dispersion and the betatron functions in the CEBAF accelerator

    International Nuclear Information System (INIS)

    Lebedev, V.A.; Bickley, M.; Schaffner, S.; Zeijts, J. van; Krafft, G.A.; Watson, C.

    1996-01-01

    During the commissioning of the CEBAF accelerator, correction of dispersion and momentum compaction, and, to a lesser extent, transverse transfer matrices were essential for robust operation. With changing machine conditions, repeated correction was found necessary. To speed the diagnostic process the authors developed a method which allows one to rapidly track the machine optics. The method is based on measuring the propagation of 30 Hz modulated betatron oscillations downstream of a point of perturbation. Compared to the usual methods of dispersion or difference orbit measurement, synchronous detection of the beam displacement, as measured by beam position monitors, offers significantly improved speed and accuracy of the measurements. The beam optics of the accelerator was altered to decrease lattice sensitivity at critical points and to simplify control of the betatron function match. The calculation of the Courant-Snyder invariant from signals of each pair of nearby beam position monitors has allowed one to perform on-line measurement and correction of the lattice properties

  13. The effects of betatron motion on the preservation of FEL microbunching

    Energy Technology Data Exchange (ETDEWEB)

    Geloni, Gianluca [European XFEL GmbH, Hamburg (Germany); Kocharyan, Vitali; Saldin, Evgeni [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-05-15

    In some options for circular polarization control at X-ray FELs, a helical radiator is placed a few ten meters distance behind the baseline undulator. If the microbunch structure induced in the baseline (planar) undulator can be preserved, intense coherent radiation is emitted in the helical radiator. The effects of betatron motion on the preservation of micro bunching in such in-line schemes should be accounting for. In this paper we present a comprehensive study of these effects. It is shown that one can work out an analytical expression for the debunching of an electron beam moving in a FODO lattice, strictly valid in the asymptote for a FODO cell much shorter than the betatron function. Further on, numerical studies can be used to demonstrate that the validity of such analytical expression goes beyond the abovementioned asymptote, and can be used in much more a general context. Finally, a comparison with Genesis simulations is given. (orig.)

  14. The effects of betatron motion on the preservation of FEL microbunching

    International Nuclear Information System (INIS)

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2011-05-01

    In some options for circular polarization control at X-ray FELs, a helical radiator is placed a few ten meters distance behind the baseline undulator. If the microbunch structure induced in the baseline (planar) undulator can be preserved, intense coherent radiation is emitted in the helical radiator. The effects of betatron motion on the preservation of micro bunching in such in-line schemes should be accounting for. In this paper we present a comprehensive study of these effects. It is shown that one can work out an analytical expression for the debunching of an electron beam moving in a FODO lattice, strictly valid in the asymptote for a FODO cell much shorter than the betatron function. Further on, numerical studies can be used to demonstrate that the validity of such analytical expression goes beyond the abovementioned asymptote, and can be used in much more a general context. Finally, a comparison with Genesis simulations is given. (orig.)

  15. Automatic Correction of Betatron Coupling in the LHC Using Injection Oscillations

    CERN Document Server

    Persson, T; Jacquet, D; Kain, V; Levinsen, Y; McAteer, M-J; Maclean, E; Skowronski, P; Tomas, R; Vanbavinckhove, G; Miyamoto, R

    2013-01-01

    The control of the betatron coupling at injection and during the energy ramp is critical for the safe operation of the tune feedback and for the dynamic aperture. In the LHC every fill is preceded by the injection of a pilot bunch with low intensity. Using the injection oscillations from the pilot bunch we are able to measure the coupling at each individual BPM. The measurement is used to calculate a global coupling correction. The correction is based on the use of two orthogonal knobs which correct the real and imaginary part of the difference resonance term f1001, respectively. This method to correct the betatron coupling has been proven successful during the normal operation of the LHC. This paper presents the method used to calculate the corrections and its performance.

  16. Successful betatron acceleration of kiloampere electron rings in RECE-Christa

    International Nuclear Information System (INIS)

    Taggart, D.P.; Parker, M.R.; Hopman, H.J.; Jayakumar, R.; Fleischmann, H.H.

    1984-01-01

    This paper reports on betatron acceleration experiments using the space-charge-neutralized electron rings in the RECE-Christa device. Magnetic probe and x-ray-absorption measurements indicate that electron ring currents of up to 2 kA were accelerated to 3.3 +- 0.3 MeV without indication of instabilities. A similar neutralization and acceleration method also appears applicable to electron rings generated in B/sub theta/-free configurations

  17. Landau damping due to tune spreads in betatron amplitude and momentum

    International Nuclear Information System (INIS)

    Lee, S.Y.; Tran, P.; Weng, W.T.

    1989-01-01

    Due to the large space charge transverse impedance in a low energy synchrotron, the coherent tune shift causes the Landau damping to be ineffective in damping the transverse coherent motion. We analyze the effect of Landau damping that is caused by the tune spreads of the betatron amplitude (space charge and/or octupole) and momentum. We find that the Landau damping becomes more significant in our two dimensional analysis. 5 refs

  18. Approximate method for calculating heat conditions in the magnetic circuits of transformers and betatrons

    International Nuclear Information System (INIS)

    Loginov, V.S.

    1986-01-01

    A technique for engineering design of two-dimensional stationary temperature field of rectangular cross section blending pile with inner heat release under nonsymmetrical cooling conditions is suggested. Area of its practical application is determined on the basis of experimental data known in literature. Different methods for calculating temperature distribution in betatron magnetic circuit are compared. Graph of maximum temperature calculation error on the basis of approximated expressions with respect to exact solution is given

  19. Experimental investigation of a small-sized betatron with superposed magnetization

    International Nuclear Information System (INIS)

    Kas'yanov, V.A.; Rychkov, M.V.; Filimonov, A.A.; Furman, Eh.G.; Chakhlov, V.L.; Chertov, A.S.; Shtejn, M.M.

    2001-01-01

    The aim of the paper is to study possibilities of small-sized betatrons (SSB) with direct current superposed magnetization (DSM). It is shown that DSM permits to decrease the SSB weight and cost of the electromagnet and capacitor storage and to shape the prolonged beam dump. It is noted that the DSM realization has the most expediency in SSB operating in a short-time mode [ru

  20. Coherent betatron instability driven by electrostatic separators: Stability analysis of the Tevatron

    International Nuclear Information System (INIS)

    Harfoush, F.A.; Bogacz, S.A.

    1989-03-01

    This paper outlines possible intensity limits due to the coherent betatron motion for the upgraded Tevatron with the electrostatic separators. Numerical simulation shows that this new vacuum chamber structure dominates the high frequency part of the coupling impedance spectrum and more likely will excite a slow head-tail instability. A simple stability analysis yields the characteristic growth-time of the unstable modes. 4 refs., 4 figs., 1 tab

  1. High-speed radiography and x-ray cinematography by high-current betatrons

    International Nuclear Information System (INIS)

    Akimochkin, Yu.V.; Akulov, G.V.; Leunov, F.G.; Moskalev, V.A.; Ryabukhin, V.L.

    1979-01-01

    The paper provides a description of an equipment system comprising a pair of 25 MeV high-current betatrons and an X-ray drum-type cinecamera for high-speed radiography and X-ray cinematography for use when studying dynamics of objects moving at a rate of 0.5 - 3.0 km/s as well as in X-ray cinematography of processes at a rate of up to 1 m/s. (author)

  2. Betatron emission as a diagnostic for injection and acceleration mechanisms in laser plasma accelerators

    International Nuclear Information System (INIS)

    Corde, S; Thaury, C; Phuoc, K Ta; Lifschitz, A; Lambert, G; Lundh, O; Brijesh, P; Sebban, S; Rousse, A; Faure, J; Malka, V; Arantchuk, L

    2012-01-01

    Betatron x-ray emission in laser plasma accelerators is a promising compact source that may be an alternative to conventional x-ray sources, based on large scale machines. In addition to its potential as a source, precise measurements of betatron emission can reveal crucial information about relativistic laser–plasma interaction. We show that the emission length and the position of the x-ray emission can be obtained by placing an aperture mask close to the source, and by measuring the beam profile of the betatron x-ray radiation far from the aperture mask. The position of the x-ray emission gives information on plasma wave breaking and hence on the laser non-linear propagation. Moreover, the measurement of the longitudinal extension helps one to determine whether the acceleration is limited by pump depletion or dephasing effects. In the case of multiple injections, it is used to retrieve unambiguously the position in the plasma of each injection. This technique is also used to study how, in a capillary discharge, the variations of the delay between the discharge and the laser pulse affect the interaction. The study reveals that, for a delay appropriate for laser guiding, the x-ray emission only occurs in the second half of the capillary: no electrons are injected and accelerated in the first half. (paper)

  3. Characteristics of a betatron core for extraction in a proton-ion medical synchrotron

    CERN Document Server

    Badano, L

    1997-01-01

    Medical synchrotrons for radiation therapy require a very stable extraction of the beam over a period of about one second. The techniques for applying resonant extraction to achieve this long spill can be classified into two groups, those that move the resonance and those that move the beam. The latter has the great advantage of keeping all lattice functions, and hence the resonance conditions, constant. The present report examines the possibility of using a betatron core to accelerate the waiting ion beam by induction into the resonance. The working principle, the proposed characteristics and the expected performances of this device are discussed. The betatron core is a smooth high-inductance device compared to the small quadrupole lenses that are normally used to move the resonance and is therefore better suited to delivering a very smooth spill. The large stored energy in a betatron core compared to a small quadrupole is also a safety feature since it responds less quickly to transients that could send lar...

  4. Advanced Simulation Capability for Environmental Management (ASCEM) Phase II Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Freshley, M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hubbard, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Flach, G. [Savannah River National Lab. (SRNL), Aiken, SC (United States); Freedman, V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Agarwal, D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Andre, B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bott, Y. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chen, X. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Davis, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Faybishenko, B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gorton, I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Murray, C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moulton, D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Meyer, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rockhold, M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shoshani, A. [LBNL; Steefel, C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wainwright, H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Waichler, S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2012-09-28

    In 2009, the National Academies of Science (NAS) reviewed and validated the U.S. Department of Energy Office of Environmental Management (EM) Technology Program in its publication, Advice on the Department of Energy’s Cleanup Technology Roadmap: Gaps and Bridges. The NAS report outlined prioritization needs for the Groundwater and Soil Remediation Roadmap, concluded that contaminant behavior in the subsurface is poorly understood, and recommended further research in this area as a high priority. To address this NAS concern, the EM Office of Site Restoration began supporting the development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific approach that uses an integration of toolsets for understanding and predicting contaminant fate and transport in natural and engineered systems. The ASCEM modeling toolset is modular and open source. It is divided into three thrust areas: Multi-Process High Performance Computing (HPC), Platform and Integrated Toolsets, and Site Applications. The ASCEM toolsets will facilitate integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. During fiscal year 2012, the ASCEM project continued to make significant progress in capabilities development. Capability development occurred in both the Platform and Integrated Toolsets and Multi-Process HPC Simulator areas. The new Platform and Integrated Toolsets capabilities provide the user an interface and the tools necessary for end-to-end model development that includes conceptual model definition, data management for model input, model calibration and uncertainty analysis, and model output processing including visualization. The new HPC Simulator capabilities target increased functionality of process model representations, toolsets for interaction with the Platform, and model confidence testing and verification for

  5. Mixed phase clouds: observations and theoretical advances (overview)

    Science.gov (United States)

    Korolev, Alexei

    2013-04-01

    Mixed phase clouds play important role in precipitation formation and radiation budget of the Earth. The microphysical measurements in mixed phase clouds are notoriously difficult due to many technical challenges. The airborne instrumentation for characterization of the microstructure of mixed phase clouds is discussed. The results multiyear airborne observations and measurements of frequency of occurrence of mixed phase, characteristic spatial scales, humidity in mixed phase and ice clouds are presented. A theoretical framework describing the thermodynamics and phase transformation of a three phase component system consisting of ice particles, liquid droplets and water vapor is discussed. It is shown that the Wegener-Bergeron-Findeisen process plays different role in clouds with different dynamics. The problem of maintenance and longevity of mixed phase clouds is discussed.

  6. Engineered Materials for Advanced Gas Turbine Engine, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop innovative composite powders and composites that will surpass the properties of currently identified materials for advanced gas turbine...

  7. Advanced Technology MEMS-based Acoustic Array, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Interdisciplinary Consulting Corporation proposes a technological advancement of current state-of-the-art acoustic energy harvester for harsh environment...

  8. Advanced Wastewater Photo-oxidation System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Pioneer Astronautics proposes an advanced photocatalytic oxidation reactor for enhancing the reliability and performance of Water Recovery Post Processing systems...

  9. A broadband gamma-ray spectrometry using novel unfolding algorithms for characterization of laser wakefield-generated betatron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Jong Ho, E-mail: jhjeon07@ibs.re.kr; Nakajima, Kazuhisa, E-mail: naka115@dia-net.ne.jp; Pathak, Vishwa Bandhu; Cho, Myung Hoon; Yoo, Byung Ju; Shin, Kang Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Kim, Hyung Taek; Sung, Jae Hee; Lee, Seung Ku; Choi, Il Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Advanced Photonics Research Institute, GIST, Gwangju 500-712 (Korea, Republic of); Rhee, Yong Joo [Nuclear Data Center, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Shin, Jung Hun; Jo, Sung Ha [Advanced Photonics Research Institute, GIST, Gwangju 500-712 (Korea, Republic of); Hojbota, Calin; Cho, Byeoung Ick; Nam, Chang Hee [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Department of Physics and Photon Science, GIST, Gwangju 500-712 (Korea, Republic of)

    2015-12-15

    We present a high-flux, broadband gamma-ray spectrometry capable of characterizing the betatron radiation spectrum over the photon energy range from 10 keV to 20 MeV with respect to the peak photon energy, spectral bandwidth, and unique discrimination from background radiations, using a differential filtering spectrometer and the unfolding procedure based on the Monte Carlo code GEANT4. These properties are experimentally verified by measuring betatron radiation from a cm-scale laser wakefield accelerator (LWFA) driven by a 1-PW laser, using a differential filtering spectrometer consisting of a 15-filter and image plate stack. The gamma-ray spectra were derived by unfolding the photostimulated luminescence (PSL) values recorded on the image plates, using the spectrometer response matrix modeled with the Monte Carlo code GEANT4. The accuracy of unfolded betatron radiation spectra was assessed by unfolding the test PSL data simulated with GEANT4, showing an ambiguity of less than 20% and clear discrimination from the background radiation with less than 10%. The spectral analysis of betatron radiation from laser wakefield-accelerated electron beams with energies up to 3 GeV revealed radiation spectra characterized by synchrotron radiation with the critical photon energy up to 7 MeV. The gamma-ray spectrometer and unfolding method presented here facilitate an in-depth understanding of betatron radiation from LWFA process and a novel radiation source of high-quality photon beams in the MeV regime.

  10. FreedomCAR Advanced Traction Drive Motor Development Phase I

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Josh (UQM Technologies, Inc.); Lutz, Jon (UQM Technologies, Inc.)

    2006-09-01

    The overall objective of this program is to design and develop an advanced traction motor that will meet the FreedomCAR and Vehicle Technologies (FCVT) 2010 goals and the traction motor technical targets. The motor specifications are given in Section 1.3. Other goals of the program include providing a cost study to ensure the motor can be developed within the cost targets needed for the automotive industry. The program has focused on using materials that are both high performance and low costs such that the performance can be met and cost targets are achieved. In addition, the motor technologies and machine design features must be compatible with high volume manufacturing and able to provide high reliability, efficiency, and ruggedness while simultaneously reducing weight and volume. Weight and volume reduction will become a major factor in reducing cost, material cost being the most significant part of manufacturing cost at high volume. Many motor technology categories have been considered in the past and present for traction drive applications, including: brushed direct current (DC), PM (PM) brushless dc (BLDC), alternating current (AC) induction, switched reluctance and synchronous reluctance machines. Of these machine technologies, PM BLDC has consistently demonstrated an advantage in terms of power density and efficiency. As rare earth magnet cost has declined, total cost may also be reduced over the other technologies. Of the many different configurations of PM BLDC machines, those which incorporate power production utilizing both magnetic torque as well as reluctance torque appear to have the most promise for traction applications. There are many different PM BLDC machine configurations which employ both of these torque producing mechanisms; however, most would fall into one of two categories--some use weaker magnets and rely more heavily on reluctance torque (reluctance-dominant PM machines), others use strong PMs and supplement with reluctance torque

  11. Photoneutron source based on a compact 10 MeV betatron

    International Nuclear Information System (INIS)

    Bell, Z.W.; Chaklov, V.L.; Golovkov, V.M.

    1998-01-01

    Accelerator-based photoneutron sources have enjoyed wide use and offer the advantages of long term stability, ease of control and absence of radioactive materials. The authors report here measurements of the yield of photoneutrons from a neutron generator using a compact betatron (466 kg total weight, 900 by 560 by 350 mm betatron dimensions) at the Institute of Introscopy of the Tomsk Polytechnic University. Electrons were accelerated to energies up to 10 MeV and produced a bremsstrahlung beam with a dose rate of 0.16 Gy/min (at 10 MeV, 1 meter from the bremsstrahlung target) to irradiate LiD, Be, depleted U, and Pb neutron-producing targets. The angular distributions of photoneutrons produced by bremsstrahlung beams were measured with a long counter and integrated to determine neutron yield. In addition, neutron time of flight spectra were recorded from all targets using a 15 meter flight path perpendicular to the photon beam. The maximum observed yields were 5.2 x 10 4 n/rad/gram target obtained with LiD, 1.7 x 10 4 n/rad/gram from Be, 3.3 x 10 3 n/rad/gram from U, and 7.5 x 10 2 n/rad/gram from Pb. Optimization of target dimensions, shape, and positioning is expected to increase the yield from the LiD target by a factor of 35. With the increased yield, this compact betatron-based system could find application in the interrogation of waste containers for fissile material

  12. Demonstration of no feasibility of a crystalline beam in a Betatron Magnet II

    International Nuclear Information System (INIS)

    Ruggiero, A.G.

    1993-01-01

    This paper investigates the feasibility of a Crystalline Beam in a weak-focusing Betatron Magnet. The curvature effect due to the bending magnet is also investigated. The case of circular one- dimensional string of electrically-charged particles is examined. It is found that the motion is unstable due to the dependence of the precession movement with the radial displacement. That is a form of negative-mass instability which can be avoided with an alternating-focussing structure. The calculation of the particle-particle interaction as well as of the forces due to the external magnetic field is done directly in the laboratory frame

  13. Thyristor current-pulse generator for betatron electromagnet with independent low-voltage supply

    International Nuclear Information System (INIS)

    Baginskii, B.A.; Makarevich, V.N.; Shtein, M.M.

    1989-01-01

    A thyristor generator is described that produces unipolar current pulses in the winding of a betatron electromagnet. The voltage on the electro-magnet is increased and the shape of the current pulses is improved by use of an intermediate inductive storage device. The current pulses have a duration of 11 msec, an amplitude of 190 A, and a repetition frequency of 50 Hz. The maximum magnetic-field energy is 450 J, the voltage on the electromagnet winding is 1.5 kV, and the supply voltage is 27 V

  14. Advanced Insulation Materials for Cryogenic Propellant Storage Applications, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Materials Technology, Inc responds to the NASA solicitation Topic X9 entitled "Propulsion and Propellant Storage" under subtopic X9-01, "Long Term Cryogenic...

  15. Modular Advanced Networked Telerobotic Interface System (MANTIS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — With the goal to reduce astronaut time required to operate experiments on the ISS and advance automated and telerobotic technology, TUI proposes to collaborate with...

  16. Advanced Gas Sensing Technology for Space Suits, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced space suits require lightweight, low-power, durable sensors for monitoring critical life support materials. No current compact sensors have the tolerance...

  17. Advanced Onboard Energy Storage Solution for Balloons, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Balloon Programs at NASA are looking for a potential 100 day missions at mid-altitudes. These balloons would be powered by solar panels to take advantage of...

  18. Advanced Vortex Hybrid Rocket Engine (AVHRE), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop a unique Advanced Vortex Hybrid Rocket Engine (AVHRE) to achieve a safe, highly-reliable, low-cost and uniquely versatile propulsion...

  19. High Performance Thrusters for Advanced Green Monopropellants, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The development of an advanced green monopropellant propulsion system could have significant benefits to a wide range of NASA space missions, from deep space...

  20. Advanced On Board Inert Gas Generation System (OBBIGS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Valcor Engineering Corporation proposes to develop an advanced On Board Inert Gas Generation System, OBIGGS, for aircraft fuel tank inerting to prevent hazardous...

  1. Advanced 3D Object Identification System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Optra will build an Advanced 3D Object Identification System utilizing three or more high resolution imagers spaced around a launch platform. Data from each imager...

  2. The Vulcan Advanced Hybrid Manufacturing System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Made In Space is developing the The Vulcan Advanced Hybrid Manufacturing System (VULCAN) to address NASA's requirement to produce high-strength, high-precision...

  3. Advanced Vortex Hybrid Rocket Engine (AVHRE), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Orbital Technologies Corporation (ORBITEC) proposes to develop a unique Advanced Vortex Hybrid Rocket Engine (AVHRE) to achieve a highly-reliable, low-cost and...

  4. Advanced Filtering Techniques Applied to Spaceflight, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — IST-Rolla developed two nonlinear filters for spacecraft orbit determination during the Phase I contract. The theta-D filter and the cost based filter, CBF, were...

  5. Advanced Technology Cloud Particle Probe for UAS, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In Phase II SPEC will design, fabricate and flight test a state-of-the-art combined cloud particle probe called the Hawkeye. Hawkeye is the culmination of two...

  6. Space-Ready Advanced Imaging System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In this Phase II effort Toyon will increase the state-of-the-art for video/image systems. This will include digital image compression algorithms as well as system...

  7. A Nanodroplet Processor for Advanced Microencapsulated Drug Formulations, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — During this Phase II program we propose to build on the key aspects of the nanodroplet encapsulation technology to demonstrate optimized formulation and...

  8. Recent Advances on Neuromorphic Systems Using Phase-Change Materials

    Science.gov (United States)

    Wang, Lei; Lu, Shu-Ren; Wen, Jing

    2017-05-01

    Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

  9. Recent Advances on Neuromorphic Systems Using Phase-Change Materials.

    Science.gov (United States)

    Wang, Lei; Lu, Shu-Ren; Wen, Jing

    2017-12-01

    Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

  10. Advanced materials for future Phase II LHC collimators

    CERN Document Server

    Dallocchio, A; Arnau Izquierdo, G; Artoos, K

    2009-01-01

    Phase I collimators, equipped with Carbon-Carbon jaws, effectively met specifications for the early phase of LHC operation. However, the choice of carbon-based materials is expected to limit the nominal beam intensity mainly because of the high RF impedance and limited efficiency of the collimators. Moreover, C/C may be degraded by high radiation doses. To overcome these limitations, new Phase II secondary collimators will complement the existing system. Their extremely challenging requirements impose a thorough material investigation effort aiming at identifying novel materials combining very diverse properties. Relevant figures of merit have been identified to classify materials: Metal-diamonds composites look a promising choice as they combine good thermal, structural and stability properties. Molybdenum is interesting for its good thermal stability. Ceramics with non-conventional RF performances are also being evaluated. The challenges posed by the development and industrialization of these materials are ...

  11. The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

    OpenAIRE

    Gupta, Digant; Lis, Christopher G; Dahlk, Sadie L; King, Jessica; Vashi, Pankaj G; Grutsch, James F; Lammersfeld, Carolyn A

    2008-01-01

    Abstract Background Bioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer. Methods We evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as ei...

  12. The effect of phase advance errors between interaction points on beam halos

    International Nuclear Information System (INIS)

    Chen, T.; Irwin, J.; Siemann, R.H.

    1995-01-01

    Phase advance errors between interaction points (IP) break the symmetry of multi-IP colliders. This symmetry breaking introduces new, lower order resonances which may chance the halo from the beam-beam interaction dramatically. In this paper, the mechanism of introducing new resonances is discussed. Simulation results showing the changes due to phase advance errors are presented. Simulation results are compared with experimental measurements at VEPP-2M

  13. Advanced worker protection system. Topical report, Phase I

    Energy Technology Data Exchange (ETDEWEB)

    Myers, J.

    1995-07-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system, maintenance, and dramatically improve worker productivity through longer duration work cycles.

  14. Recent advances in two-phase flow numerics

    International Nuclear Information System (INIS)

    Mahaffy, J.H.; Macian, R.

    1997-01-01

    The authors review three topics in the broad field of numerical methods that may be of interest to individuals modeling two-phase flow in nuclear power plants. The first topic is iterative solution of linear equations created during the solution of finite volume equations. The second is numerical tracking of macroscopic liquid interfaces. The final area surveyed is the use of higher spatial difference techniques

  15. Recent advances in two-phase flow numerics

    Energy Technology Data Exchange (ETDEWEB)

    Mahaffy, J.H.; Macian, R. [Pennsylvania State Univ., University Park, PA (United States)

    1997-07-01

    The authors review three topics in the broad field of numerical methods that may be of interest to individuals modeling two-phase flow in nuclear power plants. The first topic is iterative solution of linear equations created during the solution of finite volume equations. The second is numerical tracking of macroscopic liquid interfaces. The final area surveyed is the use of higher spatial difference techniques.

  16. Advanced Pumps and Cold Plates for Two-Phase Cooling Loops, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced instruments used for earth science missions require improved cooling systems to remove heat from high power electronic components and maintain tight...

  17. The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Grutsch James F

    2008-06-01

    Full Text Available Abstract Background Bioelectrical Impedance (BIA derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer. Methods We evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as either well-nourished or malnourished using the SGA. BIA was conducted on all patients and phase angle was calculated. The correlation between phase angle and SGA was studied using Spearman correlation coefficient. Receiver Operating Characteristic curves were estimated using the non-parametric method to determine the optimal cut-off levels of phase angle. Results Well-nourished patients had a statistically significantly higher (p = 0.005 median phase angle score (6.12 as compared to those who were malnourished (5.18. The Spearman rank correlation coefficient between phase angle and SGA was found to be 0.33 (p = 0.004, suggesting better nutritional status with higher phase angle scores. A phase angle cut-off of 5.2 was 51.7% sensitive and 79.5% specific whereas a cut-off of 6.0 was 82.8% sensitive and 54.5% specific in detecting malnutrition. Interestingly, a phase angle cut-off of 5.9 demonstrated high diagnostic accuracy in males who had failed primary treatment for advanced colorectal cancer. Conclusion Our study suggests that bioimpedance phase angle is a potential nutritional indicator in advanced colorectal cancer. Further research is needed to elucidate the optimal cut-off levels of phase angle that can be incorporated into the oncology clinic for better nutritional evaluation and management.

  18. Advanced computational model for three-phase slurry reactors

    International Nuclear Information System (INIS)

    Goodarz Ahmadi

    2001-10-01

    In the second year of the project, the Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column is further developed. The approach uses an Eulerian analysis of liquid flows in the bubble column, and makes use of the Lagrangian trajectory analysis for the bubbles and particle motions. An experimental set for studying a two-dimensional bubble column is also developed. The operation of the bubble column is being tested and diagnostic methodology for quantitative measurements is being developed. An Eulerian computational model for the flow condition in the two-dimensional bubble column is also being developed. The liquid and bubble motions are being analyzed and the results are being compared with the experimental setup. Solid-fluid mixture flows in ducts and passages at different angle of orientations were analyzed. The model predictions were compared with the experimental data and good agreement was found. Gravity chute flows of solid-liquid mixtures is also being studied. Further progress was also made in developing a thermodynamically consistent model for multiphase slurry flows with and without chemical reaction in a state of turbulent motion. The balance laws are obtained and the constitutive laws are being developed. Progress was also made in measuring concentration and velocity of particles of different sizes near a wall in a duct flow. The technique of Phase-Doppler anemometry was used in these studies. The general objective of this project is to provide the needed fundamental understanding of three-phase slurry reactors in Fischer-Tropsch (F-T) liquid fuel synthesis. The other main goal is to develop a computational capability for predicting the transport and processing of three-phase coal slurries. The specific objectives are: (1) To develop a thermodynamically consistent rate-dependent anisotropic model for multiphase slurry flows with and without chemical reaction for application to coal liquefaction. Also establish the

  19. Phase 1 Development Testing of the Advanced Manufacturing Demonstrator Engine

    Science.gov (United States)

    Case, Nicholas L.; Eddleman, David E.; Calvert, Marty R.; Bullard, David B.; Martin, Michael A.; Wall, Thomas R.

    2016-01-01

    The Additive Manufacturing Development Breadboard Engine (BBE) is a pressure-fed liquid oxygen/pump-fed liquid hydrogen (LOX/LH2) expander cycle engine that was built and operated by NASA at Marshall Space Flight Center's East Test Area. The breadboard engine was conceived as a technology demonstrator for the additive manufacturing technologies for an advanced upper stage prototype engine. The components tested on the breadboard engine included an ablative chamber, injector, main fuel valve, turbine bypass valve, a main oxidizer valve, a mixer and the fuel turbopump. All parts minus the ablative chamber were additively manufactured. The BBE was successfully hot fire tested seven times. Data collected from the test series will be used for follow on demonstration tests with a liquid oxygen turbopump and a regeneratively cooled chamber and nozzle.

  20. Correction of vertical dispersion and betatron coupling for the CLIC damping ring

    CERN Document Server

    Korostelev, M S

    2006-01-01

    The sensitivity of the CLIC damping ring to various kinds of alignment errors has been studied. Without any correction, fairly small vertical misalignments of the quadrupoles and, in particular, the sextupoles, introduce unacceptable distortions of the closed orbit as well as intolerable spurious vertical dispersion and coupling due to the strong focusing optics of the damping ring. A sophisticated beam-based correction scheme has been developed to bring the design target emittances and the dynamic aperture back to the ideal value. The correction using dipolar correctors and several skew quadrupole correctors allows a minimization of the closed-orbit distortion, the cross-talk between vertical and horizontal closed orbits, the residual vertical dispersion and the betatron coupling.

  1. Temporal profile of betatron radiation from laser-driven electron accelerators

    Czech Academy of Sciences Publication Activity Database

    Horný, Vojtěch; Nejdl, Jaroslav; Kozlová, Michaela; Krůs, Miroslav; Boháček, Karel; Petržílka, Václav; Klimo, Ondřej

    2017-01-01

    Roč. 24, č. 6 (2017), č. článku 063107. ISSN 1070-664X R&D Projects: GA ČR GA15-03118S; GA MŠk LQ1606; GA MŠk(CZ) LM2015083; GA MŠk(CZ) LD14089 EU Projects: European Commission(XE) 654148 - LASERLAB-EUROPE Grant - others:ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162; GA MŠk(CZ) LM2015042 Institutional support: RVO:61389021 ; RVO:68378271 Keywords : X-ray betatron * laser * X-ray pulses Subject RIV: BL - Plasma and Gas Discharge Physics; BL - Plasma and Gas Discharge Physics (FZU-D) OBOR OECD: Fluids and plasma physics (including surface physics); Fluids and plasma physics (including surface physics) (FZU-D) Impact factor: 2.115, year: 2016 http://aip.scitation.org/doi/full/10.1063/1.4985687

  2. Demonstration of no feasibility of a Crystalline Beam in a Betatron Magnet

    Energy Technology Data Exchange (ETDEWEB)

    Ruggiero, A.G.

    1993-09-13

    This technical report investigates the feasibility of a Crystalline Beam in a weak-focussing storage ring like a Betatron. At the same time the curvature effect due to the bending magnet is also investigated. As a special case, the example of a circular one-dimensional string of electrically charged particles is examined. It is found that the motion of the particles is unstable due to the dependence of the precession movement with respect to each other on their radial displacement. That is a form of negative-mass instability which can be avoided with an alternating-focussing structure corresponding to a transition energy above the energy of the particles. The calculation of the particle-particle interaction as well as of the forces due to the external magnetic field is done directly in the laboratory frame. The retarded potential expressions are used at this purpose.

  3. Betatron-collimation Studies for Heavy Ions in the FCC-hh

    CERN Multimedia

    Logothetis Agaliotis, Efstathios

    2018-01-01

    One of the biggest challenges in the design of the FCC-hh is the collimation system. From LHC experience it is known that a collimation system optimized for proton cleaning has a significantly reduced efficiency for heavy ions. The study presented in this contribution evaluates the betatron-collimation efficiency for the heavy-ion operation with lead nuclei at a beam energy of 50 Z TeV in the system designed for proton operation. The fragmentation processes of the main beam particles in the primary collimator are simulated with FLUKA and fragments are individually tracked with SixTrack until being lost in the downstream aperture. In this way a first-impact loss-map is obtained, identifying locations where high energy deposition are to be expected. This provides a first-level assessment of feasibility and allows to include countermeasures in the conceptual accelerator design.

  4. Performance of a correlator filter in betatron tune measurements and damping on the NSLS booster

    International Nuclear Information System (INIS)

    Galayda, J.

    1985-01-01

    A ''compensated correlator filter'', described by Kramer, et al. has been used for measurement and damping of betatron oscillations in the NSLS booster. The filter consists of a zero-degree power splitter, a 180-degree splitter, a length of 7/8'' air dielectric coaxial cable, and a short length of RG-58 cable. Connected to a beam position monitor, the output of the filter is proportional to the difference in transverse position of each bunch on subsequent turns. The useful bandwidth of the filter for damping rigid bunch oscillations extends from 10 MHz to 250 MHz, in contrast with the gigahertz bandwidth requirements for stochastic cooling, for which the filter was originally proposed. Attenuation of all rotation harmonics in this bandwidth is 40 to 60 dB

  5. Neutron doses to personnel from a 24 MeV betatron

    International Nuclear Information System (INIS)

    Beckham, W.A; Entwistle, R.F.

    1987-01-01

    Neutrons are produced by bombardment of most materials by high-energy photons. Because the x-ray shielding around high-energy x-ray generators may not have been designed with neutrons in mind there may be unexpected contributions to the radiation doses of staff working in the immediate vicinity. Neutron fluxes in the working area close to an Allis-Chalmers 24 MeV betatron have been measured using a lithium-6-loaded scintillator and the dose rates calculated. Hazard of staff has been found to be low; typical dose-equivalent rates in occupied areas range from 0.0042 to 0.012 mrem/hour. The flux of fast neutrons in the treatment room was found to be essentially zero. Measurements of neutron flux may be routinely performed using the scintillation detector (NE 912) described, and could usefully form part of the acceptance protocol for any new accelerator

  6. Betatron tomography with the use of non-linear backprojection techniques

    International Nuclear Information System (INIS)

    Baranov, V.A.; Temnik, A.K.; Chakhlov, V.L.; Chekalin, A.S.

    1995-01-01

    The testing of heavy components under non-steady-state condition (at erection and building sites, at jigs, for testing of welded joints and valving of oil and gas pipelines, power and boiler plants repair, building construction and for testing of castings and welded joints of large thickness) traditionally belongs to most pressing NDT problems. One of essential prerequisites for success at this point was the elaboration of appropriate high energy radiation sources, in particular small size pulse betatrons like MIB-4 and MIB-6 with the energy 4 and 6 MeV. Now, taking into account the new possibilities of tomography, the adaptation of fresh methods of cross-sectional visualisation (like non-linear tomosynthesis) to this conventional problem-solving area is of special interest. (orig./RHM)

  7. New microfocus bremsstrahlung source based on betatron B-18 for high-resolution radiography and tomography

    Science.gov (United States)

    Rychkov, M. M.; Kaplin, V. V.; Malikov, E. L.; Smolyanskiy, V. A.; Stepanov, I. B.; Lutsenko, A. S.; Gentsel'man, V.; Vas'kovskiy, I. K.

    2018-01-01

    New microfocus source of hard bremsstrahlung (photon energy > 1 MeV), based on the betatron B-18 with a narrow Ta target inside, for high-resolution radiography and tomography is presented. The first studies of the source demonstrate its possibilities for practical applications to detect the microdefects in products made from heavy materials and to control gaps in joints of parts of composite structures of engineering facilities. The radiography method was used to investigate a compound object consisting of four vertically arranged steel bars between which surfaces were exposed gaps of 10 μm in width. The radiographic image of the object, obtained with a magnification of 2.4, illustrates the good sensitivity of detecting the gaps between adjacent bars, due to the small width of the linear focus of the bremsstrahlung source.

  8. Federal Radiological Monitoring and Assessment Center advanced part phase response actions

    International Nuclear Information System (INIS)

    Hurley, B.

    1997-01-01

    Federal Radiological Monitoring and Assessment Center (FRMAC) response actions are carried out in Advance Party and Main Party phases of deployment. Response activities are initiated by a FRMAC Home Team prior to and during Advance Party deployment, with Home Team support continuing until the FRMAC Main Party is fully deployed. Upon arrival at the incident scene, the Advance Party establishes communications with other federal, state, and local response organizations, Following an Advance Party Meeting with these response organizations, FRMAC begins formulation of an initial monitoring and sampling plan, in coordination with the jurisdictional state and the Lead Federal Agency, and initiates detailed logistical arrangements for Main Party deployment and operations

  9. Photoneutron source based on a compact 10 MeV betatron

    International Nuclear Information System (INIS)

    Chakhlov, V.L.; Bell, Z.W.; Golovkov, V.M.; Shtein, M.M.

    1999-01-01

    Accelerator-based photoneutron sources have enjoyed wide use and offer the advantages of long term stability, ease of control and absence of radioactive materials. We report here measurements of the yield of photoneutrons from a neutron generator using a compact betatron. Electrons were accelerated to energies up to 10 MeV and produced a bremsstrahlung beam with a dose rate of 0.16 Gy/min (at 10 MeV, 1 m from the bremsstrahlung target) to irradiate LiD, Be, depleted U, and Pb neutron-producing targets. The angular distributions of photoneutrons produced by bremsstrahlung beams were measured with a 'long' counter and integrated to determine neutron yield. In addition, neutron time of flight spectra were recorded from all targets using a 15.5 m flight path perpendicular to the photon beam. The maximum observed yields were 4.6x10 7 n/s obtained with 1 kg of LiD, 5.7x10 7 n/s from a 3.3 kg Be block, 6.2x10 6 n/s from 1.5 kg of depleted U, and 7.0x10 6 n/s from 10.7 kg of Pb. Optimization of target dimensions, shape, and positioning is expected to increase the yield from the LiD target by a factor of 35, while optimization of the other targets is expected to yield at most a factor of 10. With the increased yield and a deuteride target, this compact betatron-based system could find application in the interrogation of waste containers for fissile material

  10. Advanced computational model for three-phase slurry reactors

    International Nuclear Information System (INIS)

    Goodarz Ahmadi

    2000-11-01

    In the first year of the project, solid-fluid mixture flows in ducts and passages at different angle of orientations were analyzed. The model predictions are compared with the experimental data and good agreement was found. Progress was also made in analyzing the gravity chute flows of solid-liquid mixtures. An Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column is being developed. The approach uses an Eulerian analysis of gas liquid flows in the bubble column, and makes use of the Lagrangian particle tracking procedure to analyze the particle motions. Progress was also made in developing a rate dependent thermodynamically consistent model for multiphase slurry flows in a state of turbulent motion. The new model includes the effect of phasic interactions and leads to anisotropic effective phasic stress tensors. Progress was also made in measuring concentration and velocity of particles of different sizes near a wall in a duct flow. The formulation of a thermodynamically consistent model for chemically active multiphase solid-fluid flows in a turbulent state of motion was also initiated. The general objective of this project is to provide the needed fundamental understanding of three-phase slurry reactors in Fischer-Tropsch (F-T) liquid fuel synthesis. The other main goal is to develop a computational capability for predicting the transport and processing of three-phase coal slurries. The specific objectives are: (1) To develop a thermodynamically consistent rate-dependent anisotropic model for multiphase slurry flows with and without chemical reaction for application to coal liquefaction. Also to establish the material parameters of the model. (2) To provide experimental data for phasic fluctuation and mean velocities, as well as the solid volume fraction in the shear flow devices. (3) To develop an accurate computational capability incorporating the new rate-dependent and anisotropic model for analyzing reacting and

  11. Advanced nonlinear control of three phase series active power filter

    Directory of Open Access Journals (Sweden)

    Abouelmahjoub Y.

    2014-01-01

    Full Text Available The problem of controlling three-phase series active power filter (TPSAPF is addressed in this paper in presence of the perturbations in the voltages of the electrical supply network. The control objective of the TPSAPF is twofold: (i compensation of all voltage perturbations (voltage harmonics, voltage unbalance and voltage sags, (ii regulation of the DC bus voltage of the inverter. A controller formed by two nonlinear regulators is designed, using the Backstepping technique, to provide the above compensation. The regulation of the DC bus voltage of the inverter is ensured by the use of a diode bridge rectifier which its output is in parallel with the DC bus capacitor. The Analysis of controller performances is illustrated by numerical simulation in Matlab/Simulink environment.

  12. ADVANCED COMPUTATIONAL MODEL FOR THREE-PHASE SLURRY REACTORS

    International Nuclear Information System (INIS)

    Ahmadi, Goodarz

    2004-01-01

    In this project, an Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column was developed. The approach used an Eulerian analysis of liquid flows in the bubble column, and made use of the Lagrangian trajectory analysis for the bubbles and particle motions. The bubble-bubble and particle-particle collisions are included the model. The model predictions are compared with the experimental data and good agreement was found An experimental setup for studying two-dimensional bubble columns was developed. The multiphase flow conditions in the bubble column were measured using optical image processing and Particle Image Velocimetry techniques (PIV). A simple shear flow device for bubble motion in a constant shear flow field was also developed. The flow conditions in simple shear flow device were studied using PIV method. Concentration and velocity of particles of different sizes near a wall in a duct flow was also measured. The technique of Phase-Doppler anemometry was used in these studies. An Eulerian volume of fluid (VOF) computational model for the flow condition in the two-dimensional bubble column was also developed. The liquid and bubble motions were analyzed and the results were compared with observed flow patterns in the experimental setup. Solid-fluid mixture flows in ducts and passages at different angle of orientations were also analyzed. The model predictions were compared with the experimental data and good agreement was found. Gravity chute flows of solid-liquid mixtures were also studied. The simulation results were compared with the experimental data and discussed A thermodynamically consistent model for multiphase slurry flows with and without chemical reaction in a state of turbulent motion was developed. The balance laws were obtained and the constitutive laws established

  13. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    Science.gov (United States)

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  14. Measurement of angularly dependent spectra of betatron gamma-rays from a laser plasma accelerator with quadrant-sectored range filters

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Jong Ho, E-mail: jhjeon07@ibs.re.kr; Nakajima, Kazuhisa, E-mail: naka115@dia-net.ne.jp; Rhee, Yong Joo; Pathak, Vishwa Bandhu; Cho, Myung Hoon; Shin, Jung Hun; Yoo, Byung Ju; Jo, Sung Ha; Shin, Kang Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 61005 (Korea, Republic of); Kim, Hyung Taek; Sung, Jae Hee; Lee, Seong Ku; Choi, Il Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 61005 (Korea, Republic of); Advanced Photonics Research Institute, GIST, Gwangju 61005 (Korea, Republic of); Hojbota, Calin; Bae, Lee Jin; Jung, Jaehyung; Cho, Min Sang; Cho, Byoung Ick; Nam, Chang Hee [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 61005 (Korea, Republic of); Department of Physics and Photon Science, GIST, Gwangju 61005 (Korea, Republic of)

    2016-07-15

    Measurement of angularly dependent spectra of betatron gamma-rays radiated by GeV electron beams from laser wakefield accelerators (LWFAs) are presented. The angle-resolved spectrum of betatron radiation was deconvolved from the position dependent data measured for a single laser shot with a broadband gamma-ray spectrometer comprising four-quadrant sectored range filters and an unfolding algorithm, based on the Monte Carlo code GEANT4. The unfolded gamma-ray spectra in the photon energy range of 0.1–10 MeV revealed an approximately isotropic angular dependence of the peak photon energy and photon energy-integrated fluence. As expected by the analysis of betatron radiation from LWFAs, the results indicate that unpolarized gamma-rays are emitted by electrons undergoing betatron motion in isotropically distributed orbit planes.

  15. Preliminary Studies Of A Phase Modulation Technique For Measuring Chromaticity

    International Nuclear Information System (INIS)

    Tan, C.-Y.

    2006-01-01

    The classical method for measuring chromaticity is to slowly modulate the RF frequency and then measure the betatron tune excursion. The technique that is discussed in this paper instead modulates the phase of the RF and then the chromaticity is obtained by phase demodulating the betatron tune. This technique requires knowledge of the betatron frequency in real time in order for the phase to be demodulated. Fortunately, the Tevatron has a tune tracker based on the phase locked loop principle which fits this requirement. A preliminary study with this technique has showed that it is a promising method for doing continuous chromaticity measurement and raises the possibility of doing successful chromaticity feedback with it

  16. Advanced induction machine model in phase coordinates for wind turbine applications

    DEFF Research Database (Denmark)

    Fajardo, L.A.; Iov, F.; Hansen, Anca Daniela

    2007-01-01

    In this paper an advanced phase coordinates squirrel cage induction machine model with time varying electrical parameters affected by magnetic saturation and rotor deep bar effects, is presented. The model uses standard data sheet for characterization of the electrical parameters, it is developed...

  17. Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Andersen, E; Elbaek, K

    1988-01-01

    In a phase I trial 4-demethoxydaunorubicin (4-dm DNR) was administered as oral capsules once a week to 51 adults with advanced mainly gastrointestinal solid tumors. No fatal toxicity was observed at doses up to 25.0 mg/m2. Dose-limiting granulocytopenia and non-hematologic toxicity developed...

  18. Advancement and Application of Multi-Phase CFD Modeling to High Speed Supercavitating Flows

    Science.gov (United States)

    2013-08-13

    October 2008 - December 2013 4. TITLE AND SUBTITLE Advancement and Application of Multi-Phase CFD Modeling to High Speed Supercavitating Flows...influence cavity hysteresis behavior. These observations are used to guide improved supercavitating -vehicle analyses including numerical predictions...experiments, and modeling 15. SUBJECT TERMS supercavitation , computational fluid dynamics, multiphase flow 16. SECURITY CLASSIFICATION OF: a

  19. Multiple resonance compensation for betatron coupling and its equivalence with matrix method

    CERN Document Server

    De Ninno, G

    1999-01-01

    Analyses of betatron coupling can be broadly divided into two categories: the matrix approach that decouples the single-turn matrix to reveal the normal modes and the hamiltonian approach that evaluates the coupling in terms of the action of resonances in perturbation theory. The latter is often regarded as being less exact but good for physical insight. The common opinion is that the correction of the two closest sum and difference resonances to the working point is sufficient to reduce the off-axis terms in the 4X4 single-turn matrix, but this is only partially true. The reason for this is explained, and a method is developed that sums to infinity all coupling resonances and, in this way, obtains results equivalent to the matrix approach. The two approaches is discussed with reference to the dynamic aperture. Finally, the extension of the summation method to resonances of all orders is outlined and the relative importance of a single resonance compared to all resonances of a given order is analytically desc...

  20. Positron Source from Betatron X-rays Emitted in a Plasma Wiggler

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.K.; Clayton, C.E.; Huang, C.; Joshi, C.; Lu, W.; Marsh, K.A.; Mori, W.B.; Zhou, M.; /UCLA; Barnes, C.D.; Decker, F.J.; Hogan, M.J.; Iverson, R.H.; Krejcik, P.; O' Connell, C.L.; Siemann, R.; Walz, D.R.; /SLAC; Deng, S.; Katsouleas, T.C.; Muggli, P.; Oz, E.; /Southern California U.

    2006-04-21

    In the E-167 plasma wakefield accelerator (PWFA) experiments in the Final Focus Test Beam (FFTB) at the Stanford Linear Accelerator Center (SLAC), an ultra-short, 28.5 GeV electron beam field ionizes a neutral column of Lithium vapor. In the underdense regime, all plasma electrons are expelled creating an ion column. The beam electrons undergo multiple betatron oscillations leading to a large flux of broadband synchrotron radiation. With a plasma density of 3 x 10{sup 17}cm{sup -3}, the effective focusing gradient is near 9 MT/m with critical photon energies exceeding 50 MeV for on-axis radiation. A positron source is the initial application being explored for these X-rays, as photo-production of positrons eliminates many of the thermal stress and shock wave issues associated with traditional Bremsstrahlung sources. Photo-production of positrons has been well-studied; however, the brightness of plasma X-ray sources provides certain advantages. In this paper, we present results of the simulated radiation spectra for the E-167 experiments, and compute the expected positron yield.

  1. Lifted linear phase filter banks and the polyphase-with-advance representation

    Energy Technology Data Exchange (ETDEWEB)

    Brislawn, C. M. (Christopher M.); Wohlberg, B. E. (Brendt E.)

    2004-01-01

    A matrix theory is developed for the noncausal polyphase-with-advance representation that underlies the theory of lifted perfect reconstruction filter banks and wavelet transforms as developed by Sweldens and Daubechies. This theory provides the fundamental lifting methodology employed in the ISO/IEC JPEG-2000 still image coding standard, which the authors helped to develop. Lifting structures for polyphase-with-advance filter banks are depicted in Figure 1. In the analysis bank of Figure 1(a), the first lifting step updates x{sub 0} with a filtered version of x{sub 1} and the second step updates x{sub 1} with a filtered version of x{sub 0}; gain factors 1/K and K normalize the lowpass- and highpass-filtered output subbands. Each of these steps is inverted by the corresponding operations in the synthesis bank shown in Figure 1(b). Lifting steps correspond to upper- or lower-triangular matrices, S{sub i}(z), in a cascade-form decomposition of the polyphase analysis matrix, H{sub a}(z). Lifting structures can also be implemented reversibly (i.e., losslessly in fixed-precision arithmetic) by rounding the lifting updates to integer values. Our treatment of the polyphase-with-advance representation develops an extensive matrix algebra framework that goes far beyond the results of. Specifically, we focus on analyzing and implementing linear phase two-channel filter banks via linear phase lifting cascade schemes. Whole-sample symmetric (WS) and half-sample symmetric (HS) linear phase filter banks are characterized completely in terms of the polyphase-with-advance representation. The theory benefits significantly from a number of new group-theoretic structures arising in the polyphase-with-advance matrix algebra from the lifting factorization of linear phase filter banks.

  2. Advanced gastric cancer. The findings of delayed phase dynamic CT and radiologic-histopathologic correlation

    International Nuclear Information System (INIS)

    Monzawa, Shuichi; Omata, Kosaku; Nakazima, Hiroto; Yokosuka, Noriko; Ito, Atuko; Araki, Tsutomu

    2000-01-01

    The aim of this study was to describe delayed phase dynamic CT findings of advanced (T2-T4) gastric cancer and to correlate with histopathologic findings. Quadruple phase dynamic CT including delayed imaging taken five minutes after the start of injection of contrast material was performed in 43 patients with 45 advanced gastric cancer and 20 control subjects with no gastric lesions. On delayed phase CT scans, the attenuation of the gastric wall was equal to or lower than that of the liver parenchyma in the control subjects, therefore, the presence of higher attenuation in the gastric wall was considered to be abnormal and defined as delayed enhancement. Histopathologic findings in the tumors showing delayed enhancement were compared with those in the tumors without this feature. Delayed enhancement was seen in 26 (57%) of the 45 tumors. Eleven of 25 differentiated-type tumors and 15 of 20 undifferentiated-type tumors showed delayed enhancement (p<.05). Delayed enhancement was seen in one of five medullary type tumors, in 11 of 25 intermediate-type tumors, and in 14 of 15 scirrhous-type tumors (p<.005). Delayed enhancement was frequently seen in the tumors with abundant fibrous tissue stroma. Delayed phase dynamic CT may be useful for the characterization of advanced gastric cancer. (author)

  3. Josephson phase qubit circuit for the evaluation of advanced tunnel barrier materials

    Energy Technology Data Exchange (ETDEWEB)

    Kline, Jeffrey S; Oh, Seongshik; Pappas, David P [National Institute of Standards and Technology, Boulder, CO 80305 (United States); Wang Haohua; Martinis, John M [Department of Physics, University of California, Santa Barbara, CA 93106 (United States)], E-mail: klinej@nist.gov

    2009-01-15

    We have found that crystalline Josephson junctions have problems with the control of critical current density that decrease the circuit yield. We present a superconducting quantum bit circuit designed to accommodate a factor of five variation in critical current density from one fabrication run to the next. The new design enables the evaluation of advanced tunnel barrier materials for superconducting quantum bits. Using this circuit design, we compare the performance of Josephson phase qubits fabricated with MgO and Al{sub 2}O{sub 3} advanced crystalline tunnel barriers to AlO{sub x} amorphous tunnel barrier qubits.

  4. Combined fluorescence and phase contrast imaging at the Advanced Photon Source

    International Nuclear Information System (INIS)

    Hornberger, B.; Feser, M.; Jacobsen, C.; Vogt, S.; Legnini, D.; Paterson, D.; Rehak, P.; DeGeronimo, G.; Palmer, B.M.; Experimental Facilities Division; State Univ. of New York at Stony Brook Univ.; BNL; Univ. of Vermont

    2006-01-01

    X-ray fluorescence microprobes excel at detecting and quantifying trace metals in biological and environmental science samples, but typically do not detect low Z elements such as carbon and nitrogen. Therefore, it is hard to put the trace metals into context with their natural environment. We are implementing phase contrast capabilities with a segmented detector into several microprobes at the Advanced Photon Source (APS) to address this problem. Qualitative differential phase contrast images from a modified soft x-ray detector already provide very useful information for general users. We are also implementing a quantitative method to recover the absolute phase shift by Fourier filtering detector images. New detectors are under development which are optimized for the signal levels present at the APS. In this paper, we concentrate on fundamental signal to noise considerations comparing absorption and differential phase contrast

  5. Dual-polarization interference microscopy for advanced quantification of phase associated with the image field.

    Science.gov (United States)

    Bouchal, Petr; Chmelík, Radim; Bouchal, Zdeněk

    2018-02-01

    A new concept of dual-polarization spatial light interference microscopy (DPSLIM) is proposed and demonstrated experimentally. The method works with two orthogonally polarized modes in which signal and reference waves are combined to realize the polarization-sensitive phase-shifting, thus allowing advanced reconstruction of the phase associated with the image field. The image phase is reconstructed directly from four polarization encoded interference records by a single step processing. This is a progress compared with common methods, in which the phase of the image field is reconstructed using the optical path difference and the amplitudes of interfering waves, which are calculated in multiple-step processing of the records. The DPSLIM is implemented in a common-path configuration using a spatial light modulator, which is connected to a commercial microscope Nikon E200. The optical performance of the method is demonstrated in experiments using both polystyrene microspheres and live LW13K2 cells.

  6. Recent advances in synchrotron-based hard x-ray phase contrast imaging

    Science.gov (United States)

    Liu, Y.; Nelson, J.; Holzner, C.; Andrews, J. C.; Pianetta, P.

    2013-12-01

    Ever since the first demonstration of phase contrast imaging (PCI) in the 1930s by Frits Zernike, people have realized the significant advantage of phase contrast over conventional absorption-based imaging in terms of sensitivity to ‘transparent’ features within specimens. Thus, x-ray phase contrast imaging (XPCI) holds great potential in studies of soft biological tissues, typically containing low Z elements such as C, H, O and N. Particularly when synchrotron hard x-rays are employed, the favourable brightness, energy tunability, monochromatic characteristics and penetration depth have dramatically enhanced the quality and variety of XPCI methods, which permit detection of the phase shift associated with 3D geometry of relatively large samples in a non-destructive manner. In this paper, we review recent advances in several synchrotron-based hard x-ray XPCI methods. Challenges and key factors in methodological development are discussed, and biological and medical applications are presented.

  7. Recent advances in synchrotron-based hard x-ray phase contrast imaging

    International Nuclear Information System (INIS)

    Liu, Y; Nelson, J; Andrews, J C; Pianetta, P; Holzner, C

    2013-01-01

    Ever since the first demonstration of phase contrast imaging (PCI) in the 1930s by Frits Zernike, people have realized the significant advantage of phase contrast over conventional absorption-based imaging in terms of sensitivity to ‘transparent’ features within specimens. Thus, x-ray phase contrast imaging (XPCI) holds great potential in studies of soft biological tissues, typically containing low Z elements such as C, H, O and N. Particularly when synchrotron hard x-rays are employed, the favourable brightness, energy tunability, monochromatic characteristics and penetration depth have dramatically enhanced the quality and variety of XPCI methods, which permit detection of the phase shift associated with 3D geometry of relatively large samples in a non-destructive manner. In this paper, we review recent advances in several synchrotron-based hard x-ray XPCI methods. Challenges and key factors in methodological development are discussed, and biological and medical applications are presented. (paper)

  8. Combination of light and melatonin time cues for phase advancing the human circadian clock.

    Science.gov (United States)

    Burke, Tina M; Markwald, Rachel R; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; Wright, Kenneth P

    2013-11-01

    Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Sleep and chronobiology laboratory environment free of time cues. Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

  9. Laser-wakefield accelerators for medical phase contrast imaging: Monte Carlo simulations and experimental studies

    Science.gov (United States)

    Cipiccia, S.; Reboredo, D.; Vittoria, Fabio A.; Welsh, G. H.; Grant, P.; Grant, D. W.; Brunetti, E.; Wiggins, S. M.; Olivo, A.; Jaroszynski, D. A.

    2015-05-01

    X-ray phase contrast imaging (X-PCi) is a very promising method of dramatically enhancing the contrast of X-ray images of microscopic weakly absorbing objects and soft tissue, which may lead to significant advancement in medical imaging with high-resolution and low-dose. The interest in X-PCi is giving rise to a demand for effective simulation methods. Monte Carlo codes have been proved a valuable tool for studying X-PCi including coherent effects. The laser-plasma wakefield accelerators (LWFA) is a very compact particle accelerator that uses plasma as an accelerating medium. Accelerating gradient in excess of 1 GV/cm can be obtained, which makes them over a thousand times more compact than conventional accelerators. LWFA are also sources of brilliant betatron radiation, which are promising for applications including medical imaging. We present a study that explores the potential of LWFA-based betatron sources for medical X-PCi and investigate its resolution limit using numerical simulations based on the FLUKA Monte Carlo code, and present preliminary experimental results.

  10. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING: PHASE 3R

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-09-01

    The overall objective of the Advanced Turbine System (ATS) Phase 3 Cooperative Agreement between GE and the US Department of Energy (DOE) is the development of the GE 7H and 9H combined cycle power systems. The major effort will be expended on detail design. Validation of critical components and technologies will be performed, including: hot gas path component testing, sub-scale compressor testing, steam purity test trials, and rotational heat transfer confirmation testing. Processes will be developed to support the manufacture of the first system, which was to have been sited and operated in Phase 4 but will now be sited and operated commercially by GE. This change has resulted from DOE's request to GE for deletion of Phase 4 in favor of a restructured Phase 3 (as Phase 3R) to include full speed, no load (FSNL) testing of the 7H gas turbine. Technology enhancements that are not required for the first machine design but will be critical for future ATS advances in performance, reliability, and costs will be initiated. Long-term tests of materials to confirm design life predictions will continue. A schematic of the GE H machine is shown. This report summarizes work accomplished in 2Q99.

  11. Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

    Science.gov (United States)

    Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

    2017-12-01

    Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

  12. Prototype system for phase advance measurements of LHC small beam oscillations

    CERN Document Server

    Olexa, J; Brezovic, Z; Gasior, M

    2013-01-01

    Magnet lattice parameters of the Large Hadron Collider (LHC) are measured by exciting beam transverse oscillations that allow measuring their phase advance using the beam position measurement (BPM) system. However, the BPM system requires millimetre oscillation amplitudes, with which nominal high intensity beams would cause large particle loss, dangerous for the LHC superconducting magnets. Therefore, such measurements cannot be done often, as they require special low intensity beams with important set-up time. After its first long shut-down the LHC will be equipped with new collimators with embedded BPMs, for which a new front-end electronics has been developed. Its main processing channels based on compensated diode detectors are designed for beam orbit measurement with sub-micrometre resolution. It is planned to extend this system by adding dedicated channels optimised for phase advance measurement, allowing continuous LHC optics measurement with much smaller beam excitation. This subsystem will be based o...

  13. Advanced conceptual design report. Phase II. Liquid effluent treatment and disposal Project W-252

    International Nuclear Information System (INIS)

    1995-01-01

    This Advanced Conceptual Design Report (ACDR) provides a documented review and analysis of the Conceptual Design Report (CDR), WHC-SD-W252-CDR-001, June 30, 1993. The ACDR provides further design evaluation of the major design approaches and uncertainties identified in the original CDR. The ACDR will provide a firmer basis for the both the design approach and the associated planning for the performance of the Definitive Design phase of the project

  14. Advanced Dispersed Fringe Sensing Algorithm for Coarse Phasing Segmented Mirror Telescopes

    Science.gov (United States)

    Spechler, Joshua A.; Hoppe, Daniel J.; Sigrist, Norbert; Shi, Fang; Seo, Byoung-Joon; Bikkannavar, Siddarayappa A.

    2013-01-01

    Segment mirror phasing, a critical step of segment mirror alignment, requires the ability to sense and correct the relative pistons between segments from up to a few hundred microns to a fraction of wavelength in order to bring the mirror system to its full diffraction capability. When sampling the aperture of a telescope, using auto-collimating flats (ACFs) is more economical. The performance of a telescope with a segmented primary mirror strongly depends on how well those primary mirror segments can be phased. One such process to phase primary mirror segments in the axial piston direction is dispersed fringe sensing (DFS). DFS technology can be used to co-phase the ACFs. DFS is essentially a signal fitting and processing operation. It is an elegant method of coarse phasing segmented mirrors. DFS performance accuracy is dependent upon careful calibration of the system as well as other factors such as internal optical alignment, system wavefront errors, and detector quality. Novel improvements to the algorithm have led to substantial enhancements in DFS performance. The Advanced Dispersed Fringe Sensing (ADFS) Algorithm is designed to reduce the sensitivity to calibration errors by determining the optimal fringe extraction line. Applying an angular extraction line dithering procedure and combining this dithering process with an error function while minimizing the phase term of the fitted signal, defines in essence the ADFS algorithm.

  15. Kinetic description of self-field effects on laser and betatron emission in wiggler-pumped ion-channel free electron lasers

    International Nuclear Information System (INIS)

    Alimohamadi, M; Mehdian, H; Hasanbeigi, A

    2011-01-01

    The effects of self-fields on the free electron lasers (FELs) with a helical wiggler and ion-channel guiding are considered. The steady-state orbits for a single electron in this configuration are obtained. The rate of change of axial velocity with energy, the characteristic function Φ, is derived and studied numerically. A kinetic approach has been used to get the effects of self-field on the FEL and betatron gain formula in the low-gain-pre-pass limit. It is shown that betatron gain is smaller than FEL gain. We also found a gain decrement (enhancement), arising from diamagnetism (paramagnetism) generated by the self-magnetic field for group I (group II) orbits. It is interesting that the gain enhancement is found for the non-relativistic part of group II orbits. The FEL gain and betatron gain have also been investigated for different relativistic factors γ.

  16. Evaluation of advanced two-phase flow instrumentation in SCTF Core-1

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Sobajima, Makoto; Osakabe, Masahiro; Ohnuki, Akira; Abe, Yutaka; Sudo, Yukio; Adachi, Hiromichi

    1984-03-01

    In the Slab Core Test Facility (SCTF) Core-I, advanced two-phase flow instruments have been provided by the USNRC to measure the thermohydraulic behavior in the primary system including pressure vessel during the end of blowdown, refill and reflood phases of a postulated loss-of-coolant accident in a pressurized water reactor. The advanced instruments are turbine meters, drag disks, γ-densitometers, spool pieces, liquid level detectors (LLD), fluid distribution grids (FDG), impedance probes (flag, prong and string probes), film probes, and video optical probes. This report presents evaluated results of the data from these instruments. Some instruments are quantitatively evaluated by comparing with the data from the conventional instruments or the other advanced instruments. Main conclusions are as follows: (1) The spool pieces and the γ-densitometers work well and provide satisfactory results; (2) Some of the turbine meters, the impedance probes and the film probes give partially reasonable results, but still more improvements are required; (3) Most of the LLDs, the FDGs, the impedance probes, and the film probes do not work well due to a hard cable corrosion, and (4) The video optical probes give clear image of the flow pattern. (author)

  17. Advanced Envelope Research for Factory Built Housing, Phase 3 -- Whole-House Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E.; Mullens, M.; Rath, P.

    2014-04-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing new envelope technologies. This work is part of a multi-phase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall design with exterior continuous insulation (CI). Phase 3, completed in two stages, continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.

  18. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours.

    Science.gov (United States)

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-11-17

    This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.

  19. Phase loop bandwidth measurements on the advanced photon source 352 MHz rf systems

    International Nuclear Information System (INIS)

    Horan, D.; Nassiri, A.; Schwartz, C.

    1997-01-01

    Phase loop bandwidth tests were performed on the Advanced Photon Source storage ring 352-MHz rf systems. These measurements were made using the HP3563A Control Systems Analyzer, with the rf systems running at 30 kilowatts into each of the storage ring cavities, without stored beam. An electronic phase shifter was used to inject approximately 14 degrees of stimulated phase shift into the low-level rf system, which produced measureable response voltage in the feedback loops without upsetting normal rf system operation. With the PID (proportional-integral-differential) amplifier settings at the values used during accelerator operation, the measurement data revealed that the 3-dB response for the cavity sum and klystron power-phase loops is approximately 7 kHz and 45 kHz, respectively, with the cavities the primary bandwidth-limiting factor in the cavity-sum loop. Data were taken at various PID settings until the loops became unstable. Crosstalk between the two phase loops was measured

  20. Reflooding phase after loss of coolant of an advanced pressurized water reactor with high conversion ratio

    International Nuclear Information System (INIS)

    Schumann, S.

    1984-01-01

    The emergency core cooling behaviour of an advanced pressurized water reactor (APWR) during the reflooding phase of the LOCA with double-ended break is analysed and compared to a common pressurized water reactor (PWR). The code FLUT-BS, its models and correlations are explained in detail and have been verified by numerous PWR-reflood experiments with large parameter range. The influence of core-design on ECC-behaviour as well as the influences of initial and boundary values are examined. The results show the essential differences of ECC-behaviour between PWR and APWR. (orig.) [de

  1. Computed phase equilibria for burnable neutron absorbing materials for advanced pressurized heavy water reactors

    Energy Technology Data Exchange (ETDEWEB)

    Corcoran, E.C. [Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17000, St. Forces, Kingston, Ont., K7K 7B4 (Canada)], E-mail: emily.corcoran@rmc.ca; Lewis, B.J.; Thompson, W.T. [Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17000, St. Forces, Kingston, Ont., K7K 7B4 (Canada); Hood, J. [Atomic Energy of Canada Ltd., Sheridan Park, 2251 Speakman Drive, Mississauga, Ont., L5K 1B2 (Canada); Akbari, F.; He, Z. [Atomic Energy of Canada Ltd., Chalk River Laboratories, Chalk River, Ont., K0J 1J0 (Canada); Reid, P. [Atomic Energy of Canada Ltd., Sheridan Park, 2251 Speakman Drive, Mississauga, Ont., L5K 1B2 (Canada)

    2009-03-31

    Burnable neutron absorbing materials are expected to be an integral part of the new fuel design for the Advanced CANDU [CANDU is as a registered trademark of Atomic Energy of Canada Limited.] Reactor. The neutron absorbing material is composed of gadolinia and dysprosia dissolved in an inert cubic-fluorite yttria-stabilized zirconia matrix. A thermodynamic model based on Gibbs energy minimization has been created to provide estimated phase equilibria as a function of composition and temperature. This work includes some supporting experimental studies involving X-ray diffraction.

  2. Subsonic Ultra Green Aircraft Research Phase II: N+4 Advanced Concept Development

    Science.gov (United States)

    Bradley, Marty K.; Droney, Christopher K.

    2012-01-01

    This final report documents the work of the Boeing Subsonic Ultra Green Aircraft Research (SUGAR) team on Task 1 of the Phase II effort. The team consisted of Boeing Research and Technology, Boeing Commercial Airplanes, General Electric, and Georgia Tech. Using a quantitative workshop process, the following technologies, appropriate to aircraft operational in the N+4 2040 timeframe, were identified: Liquefied Natural Gas (LNG), Hydrogen, fuel cell hybrids, battery electric hybrids, Low Energy Nuclear (LENR), boundary layer ingestion propulsion (BLI), unducted fans and advanced propellers, and combinations. Technology development plans were developed.

  3. Treatment of reduced sulphur compounds and SO2 by Gas Phase Advanced Oxidation

    DEFF Research Database (Denmark)

    Meusinger, Carl; Bluhme, Anders Brostrøm; Ingemar, Jonas L.

    2017-01-01

    Reduced sulphur compounds (RSCs) emitted from pig farms are a major problem for agriculture, due to their health and environmental impacts and foul odour. This study investigates the removal of RSCs, including H2S, and their oxidation product SO2 using Gas Phase Advanced Oxidation (GPAO). GPAO...... is a novel air cleaning technique which utilises accelerated atmospheric chemistry to oxidise pollutants before removing their oxidation products as particles. Removal efficiencies of 24.5% and 3.9% were found for 461 ppb of H2S and 714 ppb of SO2 in a laboratory system (volumetric flow Q = 75 m3/h......). A numerical model of the reactor system was developed to explore the basic features of the system; its output was in fair agreement with the experiment. The model verified the role of OH radicals in initiating the oxidation chemistry. All sulphur removed from the gas phase was detected as particulate matter...

  4. Nondestructive Evaluation of Advanced Materials with X-ray Phase Mapping

    Science.gov (United States)

    Hu, Zhengwei

    2005-01-01

    X-ray radiation has been widely used for imaging applications since Rontgen first discovered X-rays over a century ago. Its large penetration depth makes it ideal for the nondestructive visualization of the internal structure and/or defects of materials unobtainable otherwise. Currently used nondestructive evaluation (NDE) tools, X-ray radiography and tomography, are absorption-based, and work well in heavy-element materials where density or composition variations due to internal structure or defects are high enough to produce appreciable absorption contrast. However, in many cases where materials are light-weight and/or composites that have similar mass absorption coefficients, the conventional absorption-based X-ray methods for NDE become less useful. Indeed, the light-weight and ultra-high-strength requirements for the most advanced materials used or developed for current flight mission and future space exploration pose a great challenge to the standard NDE tools in that the absorption contrast arising from the internal structure of these materials is often too weak to be resolved. In this presentation, a solution to the problem, the use of phase information of X-rays for phase contrast X-ray imaging, will be discussed, along with a comparison between the absorption-based and phase-contrast imaging methods. Latest results on phase contrast X-ray imaging of lightweight Space Shuttle foam in 2D and 3D will be presented, demonstrating new opportunities to solve the challenging issues encountered in advanced materials development and processing.

  5. Advanced Envelope Research for Factory Built Housing, Phase 3. Whole-House Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States); Mullens, M. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States); Rath, P. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States)

    2014-04-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. This work is part of a multiphase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall design with exterior continuous insulation (CI). This report describes Phase 3, which was completed in two stages and continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.

  6. Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service.

    Science.gov (United States)

    Parsons, Henrique A; Baracos, Vickie E; Dhillon, Navjot; Hong, David S; Kurzrock, Razelle

    2012-01-01

    Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. Most patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMIbody composition: 215 (71-358) (BMIcancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m², independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.

  7. Advanced Envelope Research for Factory Built Housing, Phase 3 -- Design Development and Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kessler, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mullens, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Rath, P. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-01-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet the thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.

  8. Advanced Envelope Research for Factory Built Housing, Phase 3. Design Development and Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [ARIES Collaborative, New York, NY (United States); Kessler, B. [ARIES Collaborative, New York, NY (United States); Mullens, M. [ARIES Collaborative, New York, NY (United States); Rath, P. [ARIES Collaborative, New York, NY (United States)

    2014-01-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet the thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.

  9. Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

    Science.gov (United States)

    Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

    2010-09-01

    This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

  10. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma

    NARCIS (Netherlands)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J. A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with

  11. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    NARCIS (Netherlands)

    Ribas, A.; Kefford, R.; Marshall, Martin; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A.

    2013-01-01

    PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients

  12. Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells; FINAL

    International Nuclear Information System (INIS)

    Christini, R.A.; Dawless, R.K.; Ray, S.P.; Weirauch, D.A. Jr.

    2001-01-01

    During Phase I of the present program, Alcoa developed a commercial cell concept that has been estimated to save 30% of the energy required for aluminum smelting. Phase ii involved the construction of a pilot facility and operation of two pilots. Phase iii of the Advanced Anodes and Cathodes Program was aimed at bench experiments to permit the resolution of certain questions to be followed by three pilot cells. All of the milestones related to materials, in particular metal purity, were attained with distinct improvements over work in previous phases of the program. NiO additions to the ceramic phase and Ag additions to the Cu metal phase of the cermet improved corrosion resistance sufficiently that the bench scale pencil anodes met the purity milestones. Some excellent metal purity results have been obtained with anodes of the following composition: Further improvements in anode material composition appear to be dependent on a better understanding of oxide solubilities in molten cryolite. For that reason, work was commissioned with an outside consultant to model the MeO - cryolite systems. That work has led to a better understanding of which oxides can be used to substitute into the NiO-Fe2O3 ceramic phase to stabilize the ferrites and reduce their solubility in molten cryolite. An extensive number of vertical plate bench electrolysis cells were run to try to find conditions where high current efficiencies could be attained. TiB2-G plates were very inconsistent and led to poor wetting and drainage. Pure TiB2 did produce good current efficiencies at small overlaps (shadowing) between the anodes and cathodes. This bench work with vertical plate anodes and cathodes reinforced the importance of good cathode wetting to attain high current efficiencies. Because of those conclusions, new wetting work was commissioned and became a major component of the research during the third year of Phase III. While significant progress was made in several areas, much work needs to be

  13. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Hoyer, Morten; Roed, Henrik; Sengelov, Lisa; Traberg, Anders; Ohlhuis, Lars; Pedersen, Jorgen; Nellemann, Hanne; Kiil Berthelsen, Anne; Eberholst, Frey; Engelholm, Svend Aage; Maase, Hans von der

    2005-01-01

    Background and purpose: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. Patients and methods: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. Results: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. Conclusions: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma

  14. A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Chi, K.-H.; Chang, Y.-C.; Guo, W.-Y.; Leung, M.-J.; Shiau, C.-Y.; Chen, S.-Y; Wang, L.-W.; Lai, Y.-L.; Hsu, M.-M.; Lian, S.-L.; Chang, C.-H.; Liu, T.-W.; Chin, Y.-H.; Yen, S.-H.; Perng, C.-H.; Chen, Kuang Y.

    2002-01-01

    Purpose: To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC. Methods and Materials: Between November 1994 and March 1999, 157 patients with Stage IV, M 0 (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35-40 fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m 2 cisplatin, 2,200 mg/m 2 5-fluorouracil, and 120 mg/m 2 leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis. Results: With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3). Conclusions: We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival

  15. Study of the Betatron and Compton X-ray sources produced in laser wakefield acceleration of electrons

    International Nuclear Information System (INIS)

    Ferri, Julien

    2016-01-01

    An ultra-short and ultra-intense laser pulse propagating in a low-density gas can accelerate in its wake a part of the electrons ionized from the gas to relativistic energies of a few hundreds of MeV over distances of a few millimeters only. During their acceleration, as a consequence of their transverse motion, these electrons emit strongly collimated X-rays in the forward direction, which are called betatron radiations. The characteristics of this source turn it into an interesting tool for high-resolution imagery.In this thesis, we explore three different axis to work on this source using simulations on the Particles-In-Cells codes CALDER and CALDER-Circ. We first study the creation of a betatron X-ray source with kilo-joule and pico-second laser pulses, for which duration and energy are then much higher than usual in this domain. In spite of the unusual laser parameters, we show that X-ray sources can still be generated, furthermore in two different regimes.In a second study, the generally observed discrepancies between experiments and simulations are investigated. We show that the use of realistic laser profiles instead of Gaussian ones in the simulations strongly degrades the performances of the laser-plasma accelerator and of the betatron source. Additionally, this leads to a better qualitative and quantitative agreement with the experiment. Finally, with the aim of improving the X-ray emission, we explore several techniques based on the manipulation of the plasma density profile used for acceleration. We find that both the use of a transverse gradient and of a density step increases the amplitude of the electrons transverse motions, and then increases the radiated energy. Alternatively, we show that this goal can also be achieved through the transition from a laser wakefield regime to a plasma wakefield regime induced by an increase of the density. The laser wakefield optimizes the electron acceleration whereas the plasma wakefield favours the X

  16. Gas-phase advanced oxidation as an integrated air pollution control technique

    Directory of Open Access Journals (Sweden)

    Getachew A. Adnew

    2016-03-01

    Full Text Available Gas-phase advanced oxidation (GPAO is an emerging air cleaning technology based on the natural self-cleaning processes that occur in the Earth’s atmosphere. The technology uses ozone, UV-C lamps and water vapor to generate gas-phase hydroxyl radicals that initiate oxidation of a wide range of pollutants. In this study four types of GPAO systems are presented: a laboratory scale prototype, a shipping container prototype, a modular prototype, and commercial scale GPAO installations. The GPAO systems treat volatile organic compounds, reduced sulfur compounds, amines, ozone, nitrogen oxides, particles and odor. While the method covers a wide range of pollutants, effective treatment becomes difficult when temperature is outside the range of 0 to 80 °C, for anoxic gas streams and for pollution loads exceeding ca. 1000 ppm. Air residence time in the system and the rate of reaction of a given pollutant with hydroxyl radicals determine the removal efficiency of GPAO. For gas phase compounds and odors including VOCs (e.g. C6H6 and C3H8 and reduced sulfur compounds (e.g. H2S and CH3SH, removal efficiencies exceed 80%. The method is energy efficient relative to many established technologies and is applicable to pollutants emitted from diverse sources including food processing, foundries, water treatment, biofuel generation, and petrochemical industries.

  17. Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma.

    Science.gov (United States)

    Atkins, Michael; Coutinho, Anna D; Nunna, Sasikiran; Gupte-Singh, Komal; Eaddy, Michael

    2018-02-01

    The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010-September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to -10.2%). The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but

  18. Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service.

    Directory of Open Access Journals (Sweden)

    Henrique A Parsons

    Full Text Available Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown.We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI; body composition was evaluated utilizing computerized tomography(CT images. A body mass index (BMI≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria.Most patients were overweight (n = 65, 63%; 53 patients were sarcopenic (51%, including 79% of patients with a BMI<25 kg/m² and 34% of those with BMI≥25 kg/m². Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval survival (days varied according to body composition: 215 (71-358 (BMI<25 kg/m²; sarcopenic, 271 (99-443 (BMI<25 kg/m²; non-sarcopenic, 484 (286-681 (BMI≥25 kg/m²; sarcopenic; 501 d (309-693 (BMI≥25 kg/m²; non-sarcopenic. Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index.Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m², independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.

  19. Nu shifts in betatron oscillations from uniform perturbations in the presence of non-linear magnetic guide fields

    International Nuclear Information System (INIS)

    Crebbin, K.C.

    1985-05-01

    Uniform magnetic field perturbations cause a closed orbit distortion in a circular accelerator. If the magnetic guide field is non-linear these perturbations can also cause a Nu shift in the betatron oscillations. Such a shift in radial Nu values has been observed in the Bevalac while studying the low energy resonant extraction system. In the Bevalac, the radial perturbation comes from the quadrants being magnetically about 0.8% longer than 90 0 . The normal effect of this type of perturbation is a radial closed orbit shift and orbit distortion. The Nu shift, associated with this type of perturbation in the presence of a non-linear guide field, is discussed in this paper. A method of handling the non-linear n values is discussed as well as the mechanism for the associated Nu shift. Computer calculations are compared to measurements. 2 refs., 4 figs

  20. Relative measurements of fast neutron contamination in 18-MV photon beams from two linear accelerators and a betatron

    International Nuclear Information System (INIS)

    Gur, D.; Bukovitz, A.G.; Rosen, J.C.; Holmes, B.G.

    1979-01-01

    Fast neutron contamination in photon beams in the 20 MV range have been reported in recent years. In order to determine if the variations were due mainly to differences in measurement procedures, or inherent in the design of the accelerators, three different 18-MV (BJR) photon beams were compared using identical analytical techniques. The units studied were a Philips SL/75-20 and a Siemens Mevatron-20 linear accelerators and a Schimadzu betatron. Gamma spectroscopy of an activated aluminum foil was the method used. By comparing the relative amounts of neutron contamination, errors associated with absolute measurements such as detector efficiency and differences in activation foils were eliminated. Fast neutron contaminations per rad of x rays in a ratio of 6.7:3.7:1 were found for the Philips, Schimadzu and Siemens accelerators, respectively

  1. Pump requirements for betatron-generated femtosecond X-ray laser at saturation from inner-shell transitions

    International Nuclear Information System (INIS)

    Ribiere, M.; Grunenwald, J.; Ribeiro, P.; Sebban, S.; Phuoc, K.Ta; Gautier, J.; Kozlova, M.; Zeitoun, P.; Rousse, A.; Jacquemot, S.; Cheron, B.G.

    2012-01-01

    We study pump requirements to produce femtosecond X-ray laser pulses at saturation from inner-shell transitions in the amplified spontaneous emission regime. Since laser-based betatron radiation is considered as the pumping source, we first study the impact of the driving laser power on its intensity. Then we investigate the amplification behavior of the K-a transition of nitrogen at 3.2 nm (395 eV) from radiative transfer calculations coupled with kinetics modeling of the ion population densities. We show that the saturation regime may be experimentally achieved by using PW-class laser-accelerated electron bunches. Finally, we show that this X-ray laser scheme can be extended to heavier atoms and we calculate pump requirements to reach saturation at 1.5 nm (849 eV) from the K-a transition of neon. (authors)

  2. Regolith Advanced Surface Systems Operations Robot (RASSOR) Phase 2 and Smart Autonomous Sand-Swimming Excavator

    Science.gov (United States)

    Sandy, Michael

    2015-01-01

    The Regolith Advanced Surface Systems Operations Robot (RASSOR) Phase 2 is an excavation robot for mining regolith on a planet like Mars. The robot is programmed using the Robotic Operating System (ROS) and it also uses a physical simulation program called Gazebo. This internship focused on various functions of the program in order to make it a more professional and efficient robot. During the internship another project called the Smart Autonomous Sand-Swimming Excavator was worked on. This is a robot that is designed to dig through sand and extract sample material. The intern worked on programming the Sand-Swimming robot, and designing the electrical system to power and control the robot.

  3. Application of advanced statistical methods in assessment of the late phase of a nuclear accident

    International Nuclear Information System (INIS)

    Hofman, R.

    2008-01-01

    The paper presents a new methodology for improving of estimates of radiological situation on terrain in the late phase of a nuclear accident. Methods of Bayesian filtering are applied to the problem. The estimates are based on combination of modeled and measured data provided by responsible authorities. Exploiting information on uncertainty of both the data sources, we are able to produce improved estimate of the true situation on terrain. We also attempt to account for model error, which is unknown and plays crucial role in accuracy of the estimates. The main contribution of this paper is application of an approach based on advanced statistical methods, which allows for estimating of model error covariance structure upon measurements. Model error is estimated on basis of measured-minus-observed residuals evaluated upon measured and modeled values. The methodology is demonstrated on a sample scenario with simulated measurements. (authors)

  4. Advanced conceptual design report solid waste retrieval facility, phase I, project W-113

    International Nuclear Information System (INIS)

    Smith, K.E.

    1994-01-01

    Project W-113 will provide the equipment and facilities necessary to retrieve suspect transuranic (TRU) waste from Trench 04 of the 218W-4C burial ground. As part of the retrieval process, waste drums will be assayed, overpacked, vented, head-gas sampled, and x-rayed prior to shipment to the Phase V storage facility in preparation for receipt at the Waste Receiving and Processing Facility (WRAP). Advanced Conceptual Design (ACD) studies focused on project items warranting further definition prior to Title I design and areas where the potential for cost savings existed. This ACD Report documents the studies performed during FY93 to optimize the equipment and facilities provided in relation to other SWOC facilities and to provide additional design information for Definitive Design

  5. Application of advanced statistical methods in assessment of the late phase of a nuclear accident

    International Nuclear Information System (INIS)

    Hofman, R.

    2009-01-01

    The paper presents a new methodology for improving of estimates of radiological situation on terrain in the late phase of a nuclear accident. Methods of Bayesian filtering are applied to the problem. The estimates are based on combination of modeled and measured data provided by responsible authorities. Exploiting information on uncertainty of both the data sources, we are able to produce improved estimate of the true situation on terrain. We also attempt to account for model error, which is unknown and plays crucial role in accuracy of the estimates. The main contribution of this paper is application of an approach based on advanced statistical methods, which allows for estimating of model error covariance structure upon measurements. Model error is estimated on basis of measured-minus-observed residuals evaluated upon measured and modeled values. The methodology is demonstrated on a sample scenario with simulated measurements. (authors)

  6. Diffusion, Thermal Properties and Chemical Compatibilities of Select MAX Phases with Materials For Advanced Nuclear Systems

    Energy Technology Data Exchange (ETDEWEB)

    Barsoum, Michel [Drexel Univ., Philadelphia, PA (United States); Bentzel, Grady [Drexel Univ., Philadelphia, PA (United States); Tallman, Darin J. [Drexel Univ., Philadelphia, PA (United States); Sindelar, Robert [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Garcia-Diaz, Brenda [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hoffman, Elizabeth [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-04-04

    The demands of Gen IV nuclear power plants for long service life under neutron irradiation at high temperature are severe. Advanced materials that would withstand high temperatures (up to 1000+ ºC) to high doses in a neutron field would be ideal for reactor internal structures and would add to the long service life and reliability of the reactors. The objective of this work is to investigate the chemical compatibility of select MAX with potential materials that are important for nuclear energy, as well as to measure the thermal transport properties as a function of neutron irradiation. The chemical counterparts chosen for this work are: pyrolytic carbon, SiC, U, Pd, FLiBe, Pb-Bi and Na, the latter 3 in the molten state. The thermal conductivities and heat capacities of non-irradiated MAX phases will be measured.

  7. Gas-phase advanced oxidation for effective, efficient in situ control of pollution

    DEFF Research Database (Denmark)

    Johnson, Matthew Stanley; Nilsson, Elna Johanna Kristina; Svensson, Erik Anders

    2014-01-01

    In this article, gas-phase advanced oxidation, a new method for pollution control building on the photo-oxidation and particle formation chemistry occurring in the atmosphere, is introduced and characterized. The process uses ozone and UV-C light to produce in situ radicals to oxidize pollution......, generating particles that are removed by a filter; ozone is removed using a MnO2 honeycomb catalyst. This combination of in situ processes removes a wide range of pollutants with a comparatively low specific energy input. Two proof-of-concept devices were built to test and optimize the process...... particulate mass. Secondary pollution including formaldehyde and ultrafine particles might be generated, depending on the composition of the primary pollution....

  8. Parkinsonian syndromes presenting with circadian rhythm sleep disorder- advanced sleep-phase type.

    Science.gov (United States)

    Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri

    2015-01-01

    Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.

  9. Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

    2018-01-01

    The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

    Science.gov (United States)

    Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

    2013-01-01

    BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

  11. Advanced Communication and Control for Distributed Energy Resource Integration: Phase 2 Scientific Report

    Energy Technology Data Exchange (ETDEWEB)

    BPL Global

    2008-09-30

    The objective of this research project is to demonstrate sensing, communication, information and control technologies to achieve a seamless integration of multivendor distributed energy resource (DER) units at aggregation levels that meet individual user requirements for facility operations (residential, commercial, industrial, manufacturing, etc.) and further serve as resource options for electric and natural gas utilities. The fully demonstrated DER aggregation system with embodiment of communication and control technologies will lead to real-time, interactive, customer-managed service networks to achieve greater customer value. Work on this Advanced Communication and Control Project (ACCP) consists of a two-phase approach for an integrated demonstration of communication and control technologies to achieve a seamless integration of DER units to reach progressive levels of aggregated power output. Phase I involved design and proof-of-design, and Phase II involves real-world demonstration of the Phase I design architecture. The scope of work for Phase II of this ACCP involves demonstrating the Phase I design architecture in large scale real-world settings while integrating with the operations of one or more electricity supplier feeder lines. The communication and control architectures for integrated demonstration shall encompass combinations of software and hardware components, including: sensors, data acquisition and communication systems, remote monitoring systems, metering (interval revenue, real-time), local and wide area networks, Web-based systems, smart controls, energy management/information systems with control and automation of building energy loads, and demand-response management with integration of real-time market pricing. For Phase II, BPL Global shall demonstrate the Phase I design for integrating and controlling the operation of more than 10 DER units, dispersed at various locations in one or more Independent System Operator (ISO) Control Areas, at

  12. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

    Science.gov (United States)

    Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

    2002-03-01

    To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being Phase II dose. The area under the concentration time curve increased in proportion to administered dose, and the clearance remained constant over the dose range studied. Correlation analysis demonstrated relationships between dose and area under the concentration with cycle 1 hematological parameters, including absolute neutrophil and leukocyte nadirs. Bizelesin administered every 4 weeks as an i.v. push is well tolerated with dose-limiting toxicity of neutropenia. The maximum-tolerated dose (and recommended Phase II dose) is 0.8 microg/m(2) administered once every 4 weeks.

  13. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).

    Science.gov (United States)

    Weiss, Glen J; Waypa, Jordan; Blaydorn, Lisa; Coats, Jessica; McGahey, Kayla; Sangal, Ashish; Niu, Jiaxin; Lynch, Cynthia A; Farley, John H; Khemka, Vivek

    2017-06-27

    Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy. Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity. Safety monitoring and response assessments were conducted. Forty-nine patients were enrolled and treated. The most common adverse events were transaminitis, cytopenias, rash, diarrhoea, fatigue, nausea and vomiting. Arm 2 was closed due to poor accrual. The recommended phase II dose (RP2D) was determined for Arms 1, 3a, 4, 5 and 6. There were eight partial responses across multiple tumour types. Standard dose P can be safely combined with G, G+NP, G+V, I and LD. Efficacy was observed in multiple tumour types and evaluation to determine if response and duration of response are more robust than what would be expected for chemotherapy or immunotherapy alone requires further validation.

  14. Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Blasing, T.J.; Brown, R.A.; Cada, G.F.; Easterly, C.; Feldman, D.L.; Hagan, C.W.; Harrington, R.M.; Johnson, R.O.; Ketelle, R.H.; Kroodsma, R.L.; McCold, L.N.; Reich, W.J.; Scofield, P.A.; Socolof, M.L.; Taleyarkhan, R.P.; Van Dyke, J.W.

    1992-02-01

    The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production of medical and industrial isotopes such as 252 Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2

  15. Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Blasing, T.J.; Brown, R.A.; Cada, G.F.; Easterly, C.; Feldman, D.L.; Hagan, C.W.; Harrington, R.M.; Johnson, R.O.; Ketelle, R.H.; Kroodsma, R.L.; McCold, L.N.; Reich, W.J.; Scofield, P.A.; Socolof, M.L.; Taleyarkhan, R.P.; Van Dyke, J.W.

    1992-02-01

    The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production of medical and industrial isotopes such as {sup 252}Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2.

  16. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT- CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, R.

    2013-02-26

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  17. The production of radioisotopes with a betatron using an internal bombarding technique; Production de radioisotopes par bombardement interne dans un betatron; Proizvodstvo radioizotopov s pomoshch'yu betatrona s ispol'zovaniem metoda vnutrennej bombardirovki; Obtencion de radioisotopos por bombardeo interno en el betatron

    Energy Technology Data Exchange (ETDEWEB)

    Morinaga, H [Department of Physics, Tohoku University, Sendai (Japan)

    1962-01-15

    A new technique for producing radioisotopes of high specific activity with a betatron has been developed and is being used successfully. Materials to be activated are placed inside the doughnut at the end of a blind cylinder inserted from outside; thus samples are bombarded under one atmosphere just behind the bremsstrahlung target where the radiation intensity is extremely high. The saturation activity of Cu{sup 62} produced on a small piece of copper exceeded 1 mc, and the highest specific activity obtainable was approximately 500 times that produced in a conventional arrangement. So far, this internal-target technique has been used only for nuclear spectroscopy work; eight new species of radioactive isotopes (Co{sup 63}, Ga{sup 75}, As{sup 81}, In{sup 121}, In{sup 123}, Tm{sup 173}, Tm{sup 175} and Ac{sup 231}) have been identified and several new isomers have been found. The feasibility of this bombarding technique opens neiv possibilities, since medical, industrial or research betatrons may now be used, for isotope production. Short-lived isotopes are often more convenient in various applications because of their fast decay and high-energy radiation, and they may be made readily without any special skill. (author) [French] On a mis au point et utilise avec succes line technique nouvelle pour la production de radioisotopes d'activite specifique elevee dans un betatron. Les matieres a activer sont placees a l'interieur d'un tube toroidal, a l'extremite d'un cylindre a ouverture unique introduit de l'exterieur; les echantillons se trouvent ainsi bombardes, sous une atmosphere, juste derriere la cible de rayonnement de freinage, a l'endroit ou l'intensite du rayonnement est extremement elevee. L'activite de saturation du {sup 62}Cu produite sur de petits morceaux de cuivre depassait 1 millicurie et l'activite specifique la plus elevee que l'on ait pu obtenir egalait environ 500 fois l'activite produite dans un dispositif classique. Jusqu'a present, cette technique

  18. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

    OpenAIRE

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Traisathit, Patrinee; Van Gestel, Dirk

    2015-01-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan w...

  19. Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

    Science.gov (United States)

    George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

    2017-05-01

    Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of

  20. Characterization and Suppression of the Electromagnetic Interference Induced Phase Shift in the JLab FEL Photo - Injector Advanced Drive Laser System

    Energy Technology Data Exchange (ETDEWEB)

    F. G. Wilson, D. Sexton, S. Zhang

    2011-09-01

    The drive laser for the photo-cathode gun used in the JLab Free Electron Laser (FEL) facility had been experiencing various phase shifts on the order of tens of degrees (>20{sup o} at 1497 MHz or >40ps) when changing the Advanced Drive Laser (ADL) [2][3][4] micro-pulse frequencies. These phase shifts introduced multiple complications when trying to setup the accelerator for operation, ultimately inhibiting the robustness and overall performance of the FEL. Through rigorous phase measurements and systematic characterizations, we determined that the phase shifts could be attributed to electromagnetic interference (EMI) coupling into the ADL phase control loop, and subsequently resolved the issue of phase shift to within tenths of a degree (<0.5{sup o} at 1497 MHz or <1ps). The diagnostic method developed and the knowledge gained through the entire process will prove to be invaluable for future designs of similar systems.

  1. Innovative grinding wheel design for cost-effective machining of advanced ceramics. Phase I, final report

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Ramanath, S.; Simpson, M.; Lilley, E.

    1996-02-01

    Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics. This program was a cooperative effort involving three Norton groups representing a superabrasive grinding wheel manufacturer, a diamond film manufacturing division and a ceramic research center. The program was divided into two technical tasks, Task 1, Analysis of Required Grinding Wheel Characteristics, and Task 2, Design and Prototype Development. In Task 1 we performed a parallel path approach with Superabrasive metal-bond development and the higher technical risk, CVD diamond wheel development. For the Superabrasive approach, Task 1 included bond wear and strength tests to engineer bond-wear characteristics. This task culminated in a small-wheel screening test plunge grinding sialon disks. In Task 2, an improved Superabrasive metal-bond specification for low-cost machining of ceramics in external cylindrical grinding mode was identified. The experimental wheel successfully ground three types of advanced ceramics without the need for wheel dressing. The spindle power consumed by this wheel during test grinding of NC-520 sialon is as much as to 30% lower compared to a standard resin bonded wheel with 100 diamond concentration. The wheel wear with this improved metal bond was an order of magnitude lower than the resin-bonded wheel, which would significantly reduce ceramic grinding costs through fewer wheel changes for retruing and replacements. Evaluation of ceramic specimens from both Tasks 1 and 2 tests for all three ceramic materials did not show evidence of unusual grinding damage. The novel CVD-diamond-wheel approach was incorporated in this program as part of Task 1. The important factors affecting the grinding performance of diamond wheels made by CVD coating preforms were determined.

  2. Advanced direct liquefaction concepts for PETC generic units. Final report, Phase I

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    The Advanced Concepts for Direct Coal Liquefaction program was initiated by the Department of Energy in 1991 to develop technologies that could significantly reduce the cost of producing liquid fuels by the direct liquefaction of coal. The advanced 2-stage liquefaction technology that was developed at Wilsonville over the past 10 years has contributed significantly toward decreasing the cost of producing liquids from coal to about $33/bbl. It remains, however, the objective of DOE to further reduce this cost to a level more competitive with petroleum based products. This project, among others, was initiated to investigate various alternative approaches to develop technologies that might ultimately lead to a 25 % reduction in cost of product. In this project a number of novel concepts were investigated, either individually or in a coupled configuration that had the potential to contribute toward meeting the DOE goal. The concepts included mature technologies or ones closely related to them, such as coal cleaning by oil agglomeration, fluid coking and distillate hydrotreating and dewaxing. Other approaches that were either embryonic or less developed were chemical pretreatment of coal to remove oxygen, and dispersed catalyst development for application in the 2-stage liquefaction process. This report presents the results of this project. It is arranged in four sections which were prepared by participating organizations responsible for that phase of the project. A summary of the overall project and the principal results are given in this section. First, however, an overview of the process economics and the process concepts that were developed during the course of this program is presented.

  3. Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer.

    Science.gov (United States)

    Choueiri, Toni K; Plimack, Elizabeth; Arkenau, Hendrik-Tobias; Jonasch, Eric; Heng, Daniel Y C; Powles, Thomas; Frigault, Melanie M; Clark, Edwin A; Handzel, Amir A; Gardner, Humphrey; Morgan, Shethah; Albiges, Laurence; Pal, Sumanta Kumar

    2017-09-10

    Purpose Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients. Results Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P < .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema. Conclusion These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.

  4. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    Energy Technology Data Exchange (ETDEWEB)

    Caravatta, Luciana [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Padula, Gilbert D.A. [Department of Radiation Oncology, Lacks Cancer Center Saint Mary' s Health Care, Grand Rapids, MI (United States); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Ferrandina, Gabriella [Department of Gynecologic Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Mignogna, Samantha; Tambaro, Rosa [Department of Palliative Therapies, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Rossi, Marco [Department of Anaesthesia, Intensive Care, and Pain Medicine, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Flocco, Mariano [' Madre Teresa di Calcutta' Hospice, Larino (Italy); Scapati, Andrea [Department of Radiation Oncology, ' San Francesco' Hospital, Nuoro (Italy); and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  5. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    International Nuclear Information System (INIS)

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea

    2012-01-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  6. Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Sangar, Vijay K.; McBain, Catherine A.; Lyons, Jeanette; Ramani, Vijay; Logue, John; Wylie, James; Clarke, Noel W.; Cowan, Richard A.

    2005-01-01

    Purpose: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m 2 in increments of 50 mg/m 2 per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. Results: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m 2 . Dose-limiting toxicity was observed at 150 mg/m 2 with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m 2 with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. Conclusion: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m 2 , with a maximal recommended dose of 100 mg/m 2 . This dose regimen has now entered Phase II clinical trials

  7. A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.

    Science.gov (United States)

    Schelman, William R; Traynor, Anne M; Holen, Kyle D; Kolesar, Jill M; Attia, Steven; Hoang, Tien; Eickhoff, Jens; Jiang, Zhisheng; Alberti, Dona; Marnocha, Rebecca; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H

    2013-12-01

    A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%), anorexia (30.4%) and constipation (26.1%). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.

  8. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC an...

  9. Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Choi, Hye Jin; Kim, Nam-Kyu; Keum, Ki Chang; Cheon, Seong Ha; Shin, Sang Jun; Baik, Seung Hyuk; Choen, Jae Hee; Rha, Sun Young; Roh, Jae Kyung; Jeung, Hei-Cheul; Chung, Hyun Cheol; Ahn, Joong Bae

    2008-01-01

    S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable

  10. Advanced fabrication method for the preparation of MOF thin films: Liquid-phase epitaxy approach meets spin coating method.

    KAUST Repository

    Chernikova, Valeriya; Shekhah, Osama; Eddaoudi, Mohamed

    2016-01-01

    Here we report a new and advanced method for the fabrication of highly oriented/polycrystalline metal-organic framework (MOF) thin films. Building on the attractive features of the liquid-phase epitaxy (LPE) approach, a facile spin coating method

  11. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Roger R.; Flach, Greg [Savannah River National Laboratory, Savannah River Site, Bldg 773-43A, Aiken, SC 29808 (United States); Freshley, Mark D.; Freedman, Vicky; Gorton, Ian [Pacific Northwest National Laboratory, MSIN K9-33, P.O. Box 999, Richland, WA 99352 (United States); Dixon, Paul; Moulton, J. David [Los Alamos National Laboratory, MS B284, P.O. Box 1663, Los Alamos, NM 87544 (United States); Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 50B-4230, Berkeley, CA 94720 (United States); Marble, Justin [Department of Energy, 19901 Germantown Road, Germantown, MD 20874-1290 (United States)

    2013-07-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  12. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    International Nuclear Information System (INIS)

    Seitz, Roger R.; Flach, Greg; Freshley, Mark D.; Freedman, Vicky; Gorton, Ian; Dixon, Paul; Moulton, J. David; Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan; Marble, Justin

    2013-01-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  13. Advanced Si solid phase crystallization for vertical channel in vertical NANDs

    Directory of Open Access Journals (Sweden)

    Sangsoo Lee

    2014-07-01

    Full Text Available The advanced solid phase crystallization (SPC method using the SiGe/Si bi-layer structure is proposed to obtain high-mobility poly-Si thin-film transistors in next generation vertical NAND (VNAND devices. During the SPC process, the top SiGe thin film acts as a selective nucleation layer to induce surface nucleation and equiaxial microstructure. Subsequently, this SiGe thin film microstructure is propagated to the underlying Si thin film by epitaxy-like growth. The initial nucleation at the SiGe surface was clearly observed by in situ transmission electron microscopy (TEM when heating up to 600 °C. The equiaxial microstructures of both SiGe nucleation and Si channel layers were shown in the crystallized bi-layer plan-view TEM measurements. Based on these experimental results, the large-grained and less-defective Si microstructure is expected to form near the channel region of each VNAND cell transistor, which may improve the electrical characteristics.

  14. Limitations of the Conventional Phase Advance Method for Constant Power Operation of the Brushless DC Motor

    International Nuclear Information System (INIS)

    Lawler, J.S.

    2001-01-01

    The brushless dc motor (BDCM) has high-power density and efficiency relative to other motor types. These properties make the BDCM well suited for applications in electric vehicles provided a method can be developed for driving the motor over the 4 to 6:1 constant power speed range (CPSR) required by such applications. The present state of the art for constant power operation of the BDCM is conventional phase advance (CPA)[1]. In this paper, we identify key limitations of CPA. It is shown that the CPA has effective control over the developed power but that the current magnitude is relatively insensitive to power output and is inversely proportional to motor inductance. If the motor inductance is low, then the rms current at rated power and high speed may be several times larger than the current rating. The inductance required to maintain rms current within rating is derived analytically and is found to be large relative to that of BDCM designs using high-strength rare earth magnets. Th us, the CPA requires a BDCM with a large equivalent inductance

  15. Application of an advanced cost model in the different design phases of an offshore wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Hendriks, H.B.; Lindenburg, C.; Kooijman, H.J.T.; Bulder, B.H. [ECN Wind, Petten (Netherlands); Bozelie, J.; Madsen, J.B. [NEG Micon Holland, Rhenen (Netherlands); Halfschepel, R. [Van Oord ACZ, Gorinchem (Netherlands); Molenaar, W. [Ballast Nedam, Amstelveen (Netherlands); Van den Berg, R. [LM Glasfiber Holland, Heerhugowaard (Netherlands); Zaaijer, M. [TU-Delft, Delft (Netherlands)

    2001-09-01

    The goal of the Dutch Offshore Wind Energy Converter (DOWEC) consortium is to develop concepts and technology in order to make large scale offshore wind energy economically feasible. The overall DOWEC development comprises of the design, the construction, and the prototype testing. Onshore testing of a 3 MW research and development prototype is scheduled for the end of 2002. The DOWEC Concept Study aims at the choice of the optimal wind turbine concept. The wind turbine will not be treated as an isolated system. Designs of different wind turbine concepts will be evaluated as an integral part of the complete large-scale offshore wind farm. All significant properties like the structural loads, the power performance, the system reliability, the costs of the electric infrastructure, maintenance costs and installation costs is determined for the optimised designs. A quantitative ranking is then based on the cost of energy generated. Furthermore qualitative criteria like development risk and market potential will be taken into consideration when finalising the choice of concept. An advanced cost model is being developed to facilitate the above evaluation on basis of estimated energy generating costs for each concept. The same methodology will also be used in the system and detail design phase. This paper describes the DOWEC project in general, focusing at the cost modelling aspects including some preliminary results. 4 refs.

  16. Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

    Science.gov (United States)

    Wang, Ling-Wei; Hsiao, Chin-Fu; Chen, William Tzu-Liang; Lee, Hao-Hsien; Lin, Tzu-Chen; Chen, Hung-Chang; Chen, Hong-Hwa; Chien, Chun-Ru; Lin, Tze-Yi; Liu, Tsang-Wu

    2014-05-01

    To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery. © 2013 Wiley Periodicals, Inc.

  17. The influence of coupled synchrotron-betatron resonances on the extracted beam of the stretcher ring ELSA

    International Nuclear Information System (INIS)

    Neckenig, M.

    1987-09-01

    For the correction of the chromaticity for horizontal and vertical direction each four sextupoles are installed in ELSA. At a working point near 14/3 their influence on the quantity of the stable region of the transverse phase space is essentially smaller than that of the extraction sextupoles. On the other hand the latter lie at positions of low dispersion so that their influence on the chromaticity is negligible; therefore chromaticity correction and choice of the stable phase-space region are not strongly mutually dependent which will be of advance for the later operation. In extraction with corrected chromaticity the electrons are extracted only because of their different position in the transverse phase space which leads to a timely alteration of the η coordinate and by this to a migration of the extracted beam. Consequences of this are the strongly against extraction without chromaticity correction increased emittance and the doubled momentum uncertainty of the beam. Of advance however is the high extraction efficiency of 80% and the small number of the electrons remaining in the ring (below 2%). (orig./HSI) [de

  18. Advanced Nanostructured Cathode for Ultra High Specific Energy Lithium Ion Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Integrate advanced nanotechnology with energy storage technology to develop advanced cathode materials for use in Li-ion batteries while maintaining a high level of...

  19. Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

    International Nuclear Information System (INIS)

    Allal, Abdelkarim S.; Bieri, Sabine; Bruendler, Marie-Anne; Soravia, Claudio; Gertsch, Philippe; Bernier, Jacques; Morel, Philippe; Roth, Arnaud D.

    2002-01-01

    Purpose: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. Methods and Materials: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. Results: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located ≤6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). Conclusion: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a

  20. Theses. Beam studies for the CERN antiproton decelerator and a new interpretation of the resonance theory for betatron motion

    Energy Technology Data Exchange (ETDEWEB)

    De Ninno, G

    1999-07-01

    The two parts of the thesis are a mission-oriented task devoted to solve some practical problems of the Antiproton Decelerator (AD) project at CERN, and a theoretical study leading to a new method for representing and compensating betatron resonances. The AD is a new machine (at the moment under commissioning at CERN) that will allow the collection and the deceleration of an antiproton beam from 3.5 GeV/c down to 100 MeV/c (the momentum favoured for the foreseen physics experiments). The need to employ the AD magnets over a wide range required a careful study of their characteristics. The presence of a solenoid inside the AD electron cooling device generates linear coupling between the transverse degrees of freedom of the single-particle motion. Coupling can lead to operational problems and therefore a compensation scheme had tobe designed. The long-standing problem has been solved of how to establish a relationship between the two standard methods for dealing with linear coupling: the matrix approach and the Hamiltonian approach. The bridge was built by including in the Hamiltonian approach in the high frequency part of the perturbative Hamiltonian due to coupling. The procedure was generalised to the nonlinear case and, a new method was proposed for dealing both with linear and nonlinear resonances. (author)

  1. Theses. Beam studies for the CERN antiproton decelerator and a new interpretation of the resonance theory for betatron motion

    International Nuclear Information System (INIS)

    De Ninno, G.

    1999-01-01

    The two parts of the thesis are a mission-oriented task devoted to solve some practical problems of the Antiproton Decelerator (AD) project at CERN, and a theoretical study leading to a new method for representing and compensating betatron resonances. The AD is a new machine (at the moment under commissioning at CERN) that will allow the collection and the deceleration of an antiproton beam from 3.5 GeV/c down to 100 MeV/c (the momentum favoured for the foreseen physics experiments). The need to employ the AD magnets over a wide range required a careful study of their characteristics. The presence of a solenoid inside the AD electron cooling device generates linear coupling between the transverse degrees of freedom of the single-particle motion. Coupling can lead to operational problems and therefore a compensation scheme had to be designed. The long-standing problem has been solved of how to establish a relationship between the two standard methods for dealing with linear coupling: the matrix approach and the Hamiltonian approach. The bridge was built by including in the Hamiltonian approach in the high frequency part of the perturbative Hamiltonian due to coupling. The procedure was generalised to the nonlinear case and, a new method was proposed for dealing both with linear and nonlinear resonances. (author)

  2. Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.

    Science.gov (United States)

    Criner, Gerard J; Pinto-Plata, Victor; Strange, Charlie; Dransfield, Mark; Gotfried, Mark; Leeds, William; McLennan, Geoffrey; Refaely, Yael; Tewari, Sanjiv; Krasna, Mark; Celli, Bartolome

    2009-05-01

    Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling. Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema. Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life. After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life. BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

  3. On-the-Fly Kinetic Monte Carlo Simulation of Aqueous Phase Advanced Oxidation Processes.

    Science.gov (United States)

    Guo, Xin; Minakata, Daisuke; Crittenden, John

    2015-08-04

    We have developed an on-the-fly kinetic Monte Carlo (KMC) model to predict the degradation mechanisms and fates of intermediates and byproducts that are produced during aqueous-phase advanced oxidation processes (AOPs). The on-the-fly KMC model is composed of a reaction pathway generator, a reaction rate constant estimator, a mechanistic reduction module, and a KMC solver. The novelty of this work is that we develop the pathway as we march forward in time rather than developing the pathway before we use the KMC method to solve the equations. As a result, we have fewer reactions to consider, and we have greater computational efficiency. We have verified this on-the-fly KMC model for the degradation of polyacrylamide (PAM) using UV light and titanium dioxide (i.e., UV/TiO2). Using the on-the-fly KMC model, we were able to predict the time-dependent profiles of the average molecular weight for PAM. The model provided detailed and quantitative insights into the time evolution of the molecular weight distribution and reaction mechanism. We also verified our on-the-fly KMC model for the destruction of (1) acetone, (2) trichloroethylene (TCE), and (3) polyethylene glycol (PEG) for the ultraviolet light and hydrogen peroxide AOP. We demonstrated that the on-the-fly KMC model can achieve the same accuracy as the computer-based first-principles KMC (CF-KMC) model, which has already been validated in our earlier work. The on-the-fly KMC is particularly suitable for molecules with large molecular weights (e.g., polymers) because the degradation mechanisms for large molecules can result in hundreds of thousands to even millions of reactions. The ordinary differential equations (ODEs) that describe the degradation pathways cannot be solved using traditional numerical methods, but the KMC can solve these equations.

  4. A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

    Science.gov (United States)

    Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

    1992-03-01

    A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

  5. Lightweight, Efficient Power Converters for Advanced Turboelectric Aircraft Propulsion Systems, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is investigating advanced turboelectric aircraft propulsion systems that utilize superconducting motors to drive a number of distributed turbofans. In an...

  6. Palliative Radiation Therapy for Advanced Head and Neck Carcinomas: A Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Fortin, Bernard, E-mail: bfortin.hmr@ssss.gouv.qc.ca [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Khaouam, Nader [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Filion, Edith; Nguyen-Tan, Phuc Felix [Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, Quebec (Canada); Bujold, Alexis [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Lambert, Louise [Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, Quebec (Canada)

    2016-06-01

    Purpose: Incurable head and neck cancer is hard to manage with usual palliative care. Radiation therapy (RT) in this setting is sometimes omitted because there is an apprehension that the side effects in the head and neck region might counterbalance the benefits. The objective of this phase 2 study was to evaluate whether highly conformal RT could improve the therapeutic ratio with this comprehensive Quality of Life (QOL) and toxicity evaluation. Methods and Materials: Patients from 2 academic centers, deemed unfit for radical treatment because of their poor medical condition or advanced cancer stage by an experienced tumor board, were offered 25 Gy in 5 daily intensity modulated RT fractions over 1 week to the symptomatic tumor volume. QOL was evaluated with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL and QLQ-H&N35 questionnaires, and toxicities with the Common Terminology Criteria for Adverse Events version 4.0. Survival and time to tumor progression were calculated with the Kaplan-Meier method. Results: Thirty-two patients were recruited, of whom 66% had at least T4, N3, or M1 disease. The QOL questionnaires completion rate was 86%. Eighty-eight percent of patients received the planned dose. The median overall survival and progression-free survival times were, respectively, 6.5 and 3.2 months. No grade 4 or 5 toxicity was seen. Only 13% of patients had any grade 3 toxicities, and 17% of patients reported no toxicity at all. The QOL was equal or improved, and head and neck symptoms remained equal to or lower than the baseline values for most patients at up to 6 months. Eighty-five percent of patients would have chosen to receive this RT regimen again when asked. Conclusions: This palliative RT regimen was highly tolerable and effective in preserving or improving self-reported QOL in most patients for up to 6 months, which corresponds to this population's median overall survival. Given the minimal side effects

  7. Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Eisenberg, Burton L.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

    1998-01-01

    in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I and II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p = .04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) ≥ 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p = 0.017). Conclusion: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p = 0.04). Older age (≥61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

  8. Benchmarking of thermalhydraulic loop models for lead-alloy-cooled advanced nuclear energy systems. Phase I: Isothermal forced convection case

    International Nuclear Information System (INIS)

    2012-06-01

    Under the auspices of the NEA Nuclear Science Committee (NSC), the Working Party on Scientific Issues of the Fuel Cycle (WPFC) has been established to co-ordinate scientific activities regarding various existing and advanced nuclear fuel cycles, including advanced reactor systems, associated chemistry and flowsheets, development and performance of fuel and materials and accelerators and spallation targets. The WPFC has different expert groups to cover a wide range of scientific issues in the field of nuclear fuel cycle. The Task Force on Lead-Alloy-Cooled Advanced Nuclear Energy Systems (LACANES) was created in 2006 to study thermal-hydraulic characteristics of heavy liquid metal coolant loop. The objectives of the task force are to (1) validate thermal-hydraulic loop models for application to LACANES design analysis in participating organisations, by benchmarking with a set of well-characterised lead-alloy coolant loop test data, (2) establish guidelines for quantifying thermal-hydraulic modelling parameters related to friction and heat transfer by lead-alloy coolant and (3) identify specific issues, either in modelling and/or in loop testing, which need to be addressed via possible future work. Nine participants from seven different institutes participated in the first phase of the benchmark. This report provides details of the benchmark specifications, method and code characteristics and results of the preliminary study: pressure loss coefficient and Phase-I. A comparison and analysis of the results will be performed together with Phase-II

  9. Advanced nonlinear theory: Long-term stability at the SSC

    International Nuclear Information System (INIS)

    Heifets, S.

    1987-01-01

    This paper discussed the long-term stability of the particle beams in the Superconducting Super Collider. In particular the dynamics of a single particle beam is considered in depth. The topics of this paper include: the Hamiltonian of this particle approach, perturbation theory, canonical transformations, interaction of the resonances, structure of the phase space, synchro-Betatron oscillations, modulation diffusion and noise-resonance interaction. 36 refs

  10. High-quality electron beam generation and bright betatron radiation from a cascaded laser wakefield accelerator (Conference Presentation)

    Science.gov (United States)

    Liu, Jiansheng; Wang, Wentao; Li, Wentao; Qi, Rong; Zhang, Zhijun; Yu, Changhai; Wang, Cheng; Liu, Jiaqi; Qing, Zhiyong; Ming, Fang; Xu, Yi; Leng, Yuxin; Li, Ruxin; Xu, Zhizhan

    2017-05-01

    betatron radiation via manipulating the e-beam transverse oscillation in the wakefield. Very brilliant quasi-monochromatic betatron x-rays in tens of keV with significant enhancement both in photon yield and peak energy have been generated. Besides, by employing a self-synchronized all-optical Compton scattering scheme, in which the electron beam collided with the intense driving laser pulse via the reflection of a plasma mirror, we produced tunable quasi-monochromatic MeV γ-rays ( 33% full-width at half-maximum) with a peak brilliance of 3.1×1022 photons s-1 mm-2 mrad-2 0.1% BW at 1 MeV, which is one order of magnitude higher than ever reported value in MeV regime to the best of our knowledge. 1. J. S. Liu, et al., Phys. Rev. Lett. 107, 035001 (2011). 2. X. Wang, et al., Nat. Commun. 4, 1988 (2013). 3. W. P. Leemans, et al., Phys. Rev. Lett. 113, 245002 (2014) 4. W. T. Wang et al., Phys. Rev. Lett. 117, 124801 (2016). 5. Z. J. Zhang et al., Phys. Plasmas 23, 053106 (2016). 6. C. H. Yu et al., Sci. Rep. 6, 29518 (2016).

  11. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING PHASE 3 RESTRUCTURED (3R)

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2000-03-17

    This scope document defines the work scope for accomplishing the design of the GE MS7001H and MS9001H (7H and 9H) combined-cycle power systems under the original ATS Phase 3 DOE Cooperative Agreement No. DE-FC21-95MC31176, and incorporates changes in scope required to convert Phase 3 to the ''restructured'' Phase 3R as defined in Amendment A012 to the Cooperative Agreement.

  12. σ and η Phase formation in advanced polycrystalline Ni-base superalloys

    Energy Technology Data Exchange (ETDEWEB)

    Antonov, Stoichko, E-mail: santonov@hawk.iit.edu [Illinois Institute of Technology, 10 W. 32nd Street, Chicago, IL 60616 (United States); Huo, Jiajie; Feng, Qiang [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Isheim, Dieter; Seidman, David N. [Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208 (United States); Northwestern University Center for Atom Probe Tomography (NUCAPT), 2220 Campus Drive, Evanston, IL 60208 (United States); Helmink, Randolph C.; Sun, Eugene [Rolls-Royce Corporation, 450 S. Meridian Street, Indianapolis, IN 46225 (United States); Tin, Sammy [Illinois Institute of Technology, 10 W. 32nd Street, Chicago, IL 60616 (United States)

    2017-02-27

    In polycrystalline Ni-base superalloys, grain boundary precipitation of secondary phases can be significant due to the effects they pose on the mechanical properties. As new alloying concepts for polycrystalline Ni-base superalloys are being developed to extend their temperature capability, the effect of increasing levels of Nb alloying additions on long term phase stability and the formation of topologically close packed (TCP) phases needs to be studied. Elevated levels of Nb can result in increased matrix supersaturation and promote the precipitation of secondary phases. Long term thermal exposures on two experimental powder processed Ni-base superalloys containing various levels of Nb were completed to assess the stability and precipitation of TCP phases. It was found that additions of Nb promoted the precipitation of η-Ni{sub 6}AlNb along the grain boundaries in powder processed, polycrystalline Ni-base superalloys, while reduced Nb levels favored the precipitation of blocky Cr and Mo – rich σ phase precipitates along the grain boundary. Evaluation of the thermodynamic stability of these two phases in both alloys using Thermo-calc showed that while σ phase predictions are fairly accurate, predictions of the η phase are limited.

  13. Advanced Durable Flexible Ultra Low Outgassing Thermal Control Coatings for NASA Science Missions, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This Phase I program proposes to synthesize novel nanoengineered ultra low out gassing elastomers and formulate high temperature capable flexible thermal control...

  14. Biotemplated Nano-Structured Materials for Advanced Li-ion Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA has identified a critical need for pioneering advances in battery technology to give high performance, low-weight, durable and long-life power sources for...

  15. Deep UV Semiconductor Sources for Advanced Planetary Science Instruments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal addresses the need for miniature, narrow-linewidth, deep UV optical sources that operate at very low ambient temperatures for use in advanced in situ...

  16. Advanced Cathode Material For High Energy Density Lithium-Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced cathode materials having high red-ox potential and high specific capacity offer great promise to the development of high energy density lithium-based...

  17. Advanced Optical Metrology for XRAY Replication Mandrels and Mirrors, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced x-ray observatories such as IXO and GenX will require thousands of thin shell mirror segments produced by replication using convex mandrels. Quality and...

  18. Space Station Validation of Advanced Radiation-Shielding Polymeric Materials, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In Subtopic X11.01, NASA has identified the need to develop advanced radiation-shielding materials and systems to protect humans from the hazards of space radiation...

  19. Advanced Air Evaporation System with Reusable Wicks for Water Recovery, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A microgravity-compatible Advanced Air Evaporation System (AAES) is proposed for recovering nearly 100% of water from highly contaminated wastewater without concern...

  20. Nucleosynthesis in advanced phases of stellar evolution: comparison between theory and observation

    International Nuclear Information System (INIS)

    Pacheco, J.A.F.

    1990-01-01

    The contamination of stellar atmospheres in advanced stages of evolution is studied, comparing observable data with theoretical expectations. The observable contaminations in some specific stars are presented. (M.C.K.)

  1. High Efficiency Advanced Lightweight Fuel Cell (HEAL-FC), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Infinity's High Efficiency Advanced Lightweight Fuel Cell (HEAL FC) is an improved version of its current fuel cell technology developed for space applications. The...

  2. Advanced Solid-State Joining Processes for 2219 Aluminum Alloys, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Thermal Stir Welding (TSW) advances the more conventional Friction Stir Welding (C-FSW) process by separating the primary process variables of metal stirring and...

  3. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal and management (APWR) system for incorporation into Polymer...

  4. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal (APWR) system for Polymer Electrolyte Membrane (PEM)...

  5. Integrated Advanced Monopropellant CMC Thruster / Thermal Stand-Off Assembly, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — High performance non-toxic monopropellants offer significant benefits relative to the current state-of-the-art. The benefits of these advanced monopropellants (AMP)...

  6. Development of Advanced Anti-Reflection Coatings for High Performance Solar Energy Applications, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — MicroLink Devices will increase the efficiency of multi-junction solar cells by designing and demonstrating advanced anti-reflection coatings (ARCs) that will...

  7. Development of Advanced Anti-Reflection Coatings for High Performance Solar Energy Applications, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — MicroLink and its subcontractor Magnolia Solar will develop and demonstrate advanced anti-reflection coating (ARC) designs that will provide a better broadband and...

  8. Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

    Science.gov (United States)

    2018-01-02

    Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma

  9. Metal Advanced Manufacturing Bot-Assisted Assembly (MAMBA) Process, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Tethers Unlimited, Inc. (TUI) proposes to develop the Metal Advanced Manufacturing Bot-Assisted Assembly (MAMBA) Process, a robotically managed metal press and...

  10. Life prediction methodology for ceramic components of advanced heat engines. Phase 1: Volume 1, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cuccio, J.C.; Brehm, P.; Fang, H.T. [Allied-Signal Aerospace Co., Phoenix, AZ (United States). Garrett Engine Div.] [and others

    1995-03-01

    Emphasis of this program is to develop and demonstrate ceramics life prediction methods, including fast fracture, stress rupture, creep, oxidation, and nondestructive evaluation. Significant advancements were made in these methods and their predictive capabilities successfully demonstrated.

  11. Non-Intrusive, Distributed Gas Sensing Technology for Advanced Spacesuits, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advances in spacesuits are required to support the ISS and future human exploration. Spacesuit development and ground-based testing tasks require sensing and...

  12. Aluminum-centered tetrahedron-octahedron transition in advancing Al-Sb-Te phase change properties.

    Science.gov (United States)

    Xia, Mengjiao; Ding, Keyuan; Rao, Feng; Li, Xianbin; Wu, Liangcai; Song, Zhitang

    2015-02-24

    Group IIIA elements, Al, Ga, or In, etc., doped Sb-Te materials have proven good phase change properties, especially the superior data retention ability over popular Ge2Sb2Te5, while their phase transition mechanisms are rarely investigated. In this paper, aiming at the phase transition of Al-Sb-Te materials, we reveal a dominant rule of local structure changes around the Al atoms based on ab initio simulations and nuclear magnetic resonance evidences. By comparing the local chemical environments around Al atoms in respective amorphous and crystalline Al-Sb-Te phases, we believe that Al-centered motifs undergo reversible tetrahedron-octahedron reconfigurations in phase transition process. Such Al-centered local structure rearrangements significantly enhance thermal stability of amorphous phase compared to that of undoped Sb-Te materials, and facilitate a low-energy amorphization due to the weak links among Al-centered and Sb-centered octahedrons. Our studies may provide a useful reference to further understand the underlying physics and optimize performances of all IIIA metal doped Sb-Te phase change materials, prompting the development of NOR/NAND Flash-like phase change memory technology.

  13. Animal-vehicle crash mitigation using advanced technology : phase II, system effectiveness and system acceptance.

    Science.gov (United States)

    2009-03-01

    This project was initiated in the fall of 1999. The results through the fall of 2005 (Phase I) have been documented in detail in an earlier report. The accomplishments of Phase I included the following: the identification of existing animal detection...

  14. Fundamental Studies on Phase Transformations and Mechanical Properties of Fusion Welds in Advanced Naval Steels

    Science.gov (United States)

    2017-07-31

    naval and structural applications. However, prior to this research project, a fundamental understanding of the phase transformation behavior under the...prior to this research project, a fundamental understanding of the phase transformation behavior under the high heating and cooling rates associated...HAZ mechanical properties. Such a treatment is expensive, time consuming , and cannot be practically applied to large structures. However, the absence

  15. Two-phase flow measurements with advanced instrumented spool pieces and local conductivity probes

    International Nuclear Information System (INIS)

    Turnage, K.G.; Davis, C.E.

    1979-01-01

    A series of two-phase, air-water and steam-water tests performed with instrumented spool pieces and with conductivity probes obtained from Atomic Energy of Canada, Ltd. is described. The behavior of the three-beam densitometer, turbine meter, and drag flowmeter is discussed in terms of two-phase models. Application of some two-phase mass flow models to the recorded spool piece data is made and preliminary results are shown. Velocity and void fraction information derived from the conductivity probes is presented and compared to velocities and void fractions obtained using the spool piece instrumentation

  16. Phase I dose escalating trial of hyperfractinated pre-operative chemoradiation for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle M.; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

    1997-01-01

    ). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p 2 04). This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

  17. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase II project...

  18. Composite advanced polymers for low moisture and oxygen permeability, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase I program addresses NASA?s need for long duration shelf stable food by developing a high oxygen/moisture barrier...

  19. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase I project...

  20. Advanced Nongray Radiation Module in the LOCI Framework for Combustion CFD, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Radiative heat fluxes are important in the design of launch vehicles for Project Constellation. In this Phase II STTR, CFDRC and its partner Mississippi State...

  1. Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

    Science.gov (United States)

    Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

    2017-11-28

    Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

  2. An advanced ultrasonic technique for slow and void fraction measurements of two-phase flow

    International Nuclear Information System (INIS)

    Faccini, J.L.H.; Su, J.; Harvel, G.D.; Chang, J.S.

    2004-01-01

    In this paper, we present a hybrid type counterpropagating transmission ultrasonic technique (CPTU) for flow and time averaging ultrasonic transmission intensity void fraction measurements (TATIU) of air-water two-phase flow, which is tested in the new two-phase flow test section mounted recently onto an existing single phase flow rig. The circular pipe test section is made of 51.2 mm stainless steel, followed by a transparent extruded acrylic pipe aimed at flow visualization. The two-phase flow rig operates in several flow regimes: bubbly, smooth stratified, wavy stratified and slug flow. The observed flow patterns are compared with previous experimental and numerical flow regime map for horizontal two phase flows. These flow patterns will be identified by time averaging transmission intensity ultrasonic techniques which have been developed to meet this particular application. A counterpropagating transmission ultrasonic flowmeter is used to measure the flow rate of liquid phase. A pulse-echo TATIU ultrasonic technique used to measure the void fraction of the horizontal test section is presented. We can draw the following conclusions: 1) the ultrasonic system was able to characterize the 2 flow patterns simulated (stratified and plug flow); 2) the results obtained for water volumetric fraction require more experimental work to determine exactly the technique uncertainties but, a priori, they are consistent with earlier work; and 3) the experimental uncertainties can be reduced by improving the data acquisition system, changing the acquisition time interval from seconds to milliseconds

  3. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, E; Sørensen, J B

    2010-01-01

    Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participa...

  4. Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study

    DEFF Research Database (Denmark)

    Urup, Thomas; Pawlak, W Z; Petersen, P M

    2013-01-01

    Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin...... combined with docetaxel as first-line treatment of advanced ACC....

  5. Utility advanced turbine systems (ATS) technology readiness testing -- Phase 3. Annual report, October 1, 1996--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The overall objective of the Advanced Turbine System (ATS) Phase 3 Cooperative Agreement between GE and the US Department of Energy (DOE) is the development of the GE 7H and 9H combined cycle power systems. The major effort will be expended on detail design. Validation of critical components and technologies will be performed including: hot gas path component testing, sub-scale compressor testing, steam purity test trials, and rotational heat transfer confirmation testing. Processes will be developed to support the manufacture of the first system. Technology enhancements that are not required for the first machine design but will be critical for future ATS advances in performance, reliability, and costs will be initiated. Long-term tests of materials to confirm design life predictions will continue. A schematic of the GE H machine is shown.

  6. Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

    Science.gov (United States)

    Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

    2016-01-01

    Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible

  7. Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial.

    Science.gov (United States)

    Pavlakis, Nick; Sjoquist, Katrin M; Martin, Andrew J; Tsobanis, Eric; Yip, Sonia; Kang, Yoon-Koo; Bang, Yung-Jue; Alcindor, Thierry; O'Callaghan, Christopher J; Burnell, Margot J; Tebbutt, Niall C; Rha, Sun Young; Lee, Jeeyun; Cho, Jae-Yong; Lipton, Lara R; Wong, Mark; Strickland, Andrew; Kim, Jin Won; Zalcberg, John R; Simes, John; Goldstein, David

    2016-08-10

    We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma. We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014. A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported. In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned. © 2016 by American Society of Clinical Oncology.

  8. Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

    Science.gov (United States)

    Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

    2015-02-01

    The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

  9. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    Science.gov (United States)

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  10. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

    Science.gov (United States)

    Wells, Samuel A; Robinson, Bruce G; Gagel, Robert F; Dralle, Henning; Fagin, James A; Santoro, Massimo; Baudin, Eric; Elisei, Rossella; Jarzab, Barbara; Vasselli, James R; Read, Jessica; Langmuir, Peter; Ryan, Anderson J; Schlumberger, Martin J

    2012-01-10

    There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

  11. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer

    DEFF Research Database (Denmark)

    Cerbone, L; Sternberg, C N; Sengeløv, L

    2016-01-01

    BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim...... × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles. CONCLUSIONS: Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1...

  12. AISI/DOE Advanced Process Control Program Vol. 5 of 6: Phase Measurement of Galvanneal

    Energy Technology Data Exchange (ETDEWEB)

    Cristopher Burnett; Ronald Guel; James R. Philips; L. Lowry; Beverly Tai

    1999-05-31

    Augmentation of the internal software of a commercial X-ray fluorescence gauge is shown to enable the instrument to extend its continuous on-line real-time measurements of a galvanneal coating's total elemental content to encompass similar measurements of the relative thickness of the coating's three principal metallurgical phases. The mathematical structure of this software augmentation is derived from the theory of neural networks. The performance of the augmented gauge is validated by comparing the gauge implied real-time phase distribution with the phase distribution independently measured off-line on between the gauge and laboratory measurements and to suggest preferred approaches to be followed in future application of the augmented gauge.

  13. A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

    2016-08-17

    This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

  14. Advanced supersonic propulsion study, phases 3 and 4. [variable cycle engines

    Science.gov (United States)

    Allan, R. D.; Joy, W.

    1977-01-01

    An evaluation of various advanced propulsion concepts for supersonic cruise aircraft resulted in the identification of the double-bypass variable cycle engine as the most promising concept. This engine design utilizes special variable geometry components and an annular exhaust nozzle to provide high take-off thrust and low jet noise. The engine also provides good performance at both supersonic cruise and subsonic cruise. Emission characteristics are excellent. The advanced technology double-bypass variable cycle engine offers an improvement in aircraft range performance relative to earlier supersonic jet engine designs and yet at a lower level of engine noise. Research and technology programs required in certain design areas for this engine concept to realize its potential benefits include refined parametric analysis of selected variable cycle engines, screening of additional unconventional concepts, and engine preliminary design studies. Required critical technology programs are summarized.

  15. DE-FOA-EE0005502 Advanced Percussive Drilling Technology for Geothermal Exploration and Development Phase II Report.

    Energy Technology Data Exchange (ETDEWEB)

    Su, Jiann-Cherng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Raymond, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Prasad, Somuri V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfer, Dale R. [Atlas-Copco Secoroc, LLC, Fagersta (Sweden)

    2017-05-01

    Percussive hammers are a promising advance in drilling technology for geothermal since they rely upon rock reduction mechanisms that are well-suited for use in the hard, brittle rock characteristic of geothermal formations. The project research approach and work plan includes a critical path to development of a high-temperature (HT) percussive hammer using a two- phase approach. The work completed in Phase I of the project demonstrated the viability of percussive hammers and that solutions to technical challenges in design, material technology, and performance are likely to be resolved. Work completed in Phase II focused on testing the findings from Phase I and evaluating performance of the materials and designs at high- operating temperatures. A high-operating temperature (HOT) drilling facility was designed, built, and used to test the performance of the DTH under extreme conditions. Results from the testing indicate that a high-temperature capable hammer can be developed and is a viable alternative for user in the driller's toolbox.

  16. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    Energy Technology Data Exchange (ETDEWEB)

    Trip, Anouk K. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Poppema, Boelo J. [Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Siemerink, Ester [Department of Internal Medicine, Ziekenhuisgroep Twente, Hengelo (Netherlands); Beukema, Jannet C. [Department of Radiation Oncology, University Medical Centre Groningen (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Plukker, John T.M. [Department of Surgical Oncology, University Medical Centre Groningen (Netherlands); Richel, Dick J. [Department of Medical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Hulshof, Maarten C.C.M. [Department of Radiation Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Sandick, Johanna W. van [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Cats, Annemieke [Department of Gastroenterology and Hepatology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jansen, Edwin P.M. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Hospers, Geke A.P., E-mail: g.a.p.hospers@umcg.nl [Department of Medical Oncology, University Medical Centre Groningen (Netherlands)

    2014-08-15

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.

  17. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    International Nuclear Information System (INIS)

    Trip, Anouk K.; Poppema, Boelo J.; Berge Henegouwen, Mark I. van; Siemerink, Ester; Beukema, Jannet C.; Verheij, Marcel; Plukker, John T.M.; Richel, Dick J.; Hulshof, Maarten C.C.M.; Sandick, Johanna W. van; Cats, Annemieke; Jansen, Edwin P.M.; Hospers, Geke A.P.

    2014-01-01

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates

  18. Advanced Coating Technology for Enhanced Performance of Microchannel Plates for UV Detectors, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In this NASA SBIR Phase I proposal we propose to apply a highly conformal coating of ZnO and AlN or a double layer of GaN to the surface and internal pore walls of...

  19. Recent Advances in Atmospheric Vapor-Phase Deposition of Transparent and Conductive Zinc Oxide

    NARCIS (Netherlands)

    Illiberi, A.; Poodt, P.; Roozeboom, F.

    2014-01-01

    The industrial need for high-throughput and low-cost ZnO deposition processes has triggered the development of atmospheric vapor-phase deposition techniques which can be easily applied to continuous, in-line manufacturing. While atmospheric CVD is a mature technology, new processes for the growth of

  20. Advanced high speed X-ray CT scanner for measurement and visualization of multi-phase flow

    International Nuclear Information System (INIS)

    Hori, Keiichi; Fujimoto, Tetsuro; Kawanishi, Kohei; Nishikawa, Hideo

    1998-01-01

    The development of an ultra-fast X-ray computed tomography (CT) scanner has been performed. The object of interest is in a transient or unsettled state, which makes the conventional CT scanner inappropriate. A concept of electrical switching of electron beam of X-ray generation unit is adopted to reduce the scanning time instead of a mechanical motion adopted by a conventional CT scanner. The mechanical motion is a major obstacle to improve the scanning speed. A prototype system with a scanning time of 3.6 milliseconds was developed at first. And, the feasibility was confirmed to measure the dynamic events of two-phase flow. However, faster scanning speed is generally required for the practical use in the thermalhydraulics research field. Therefore, the development of advanced type has been performed. This advanced type can operate under the scanning time of 0.5 milliseconds and is applicable for the measurement of the multi-phase flow with velocity up to 4-5 m/s. (author)

  1. The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters as measured by radiotelemetry in rats

    International Nuclear Information System (INIS)

    Molcan, L; Vesela, A; Zeman, M; Teplan, M

    2013-01-01

    Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian–ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian–ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases. (paper)

  2. Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

    International Nuclear Information System (INIS)

    Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

  3. Study of Second Phase Particles and Fe content in Zr Alloys Using the Advanced Photon Source at Argonne

    Energy Technology Data Exchange (ETDEWEB)

    Arthur T. Motta

    2001-11-07

    We have conducted a study of second phase particles and matrix alloying element concentrations in zirconium alloys using synchrotron radiation from the Advanced Photon Source (APS) at Argonne National Laboratory. The high flux of synchrotron radiation delivered at the 2BM beamline compared to conventional x-ray generators, enables the detection of very small precipitate volume fractions. We detected the standard C14 hcp Zr(Cr,Fe)2 precipitates, (the stable second phase in Zircaloy-4) in the bulk material at a cumulative annealing parameter as low as 10-20 h, and we followed the kinetics of precipitation and growth as a function of the cumulative annealing parameter (CAP) in the range 10-22 (quench) to 10-16 h. In addition, the unique combination of spatial resolution and elemental sensitivity of the 2ID-D/E microbeam line at the Advanced Photon Source at Argonne (APS) allows study of the alloying element concentrations at ppm levels in an area as small as 0.2 mm. We used x-ray fluorescence induced by this sub-micron x-ray beam to determine the concentration of these alloying elements in the matrix as a function of alloy type and thermal history. We discuss these results and the potential of synchrotron radiation-based techniques for studying zirconium alloys.

  4. Study of Second Phase Particles and Fe content in Zr Alloys Using the Advanced Photon Source at Argonne

    International Nuclear Information System (INIS)

    Motta, Arthur T.

    2001-01-01

    We have conducted a study of second phase particles and matrix alloying element concentrations in zirconium alloys using synchrotron radiation from the Advanced Photon Source (APS) at Argonne National Laboratory. The high flux of synchrotron radiation delivered at the 2BM beamline compared to conventional x-ray generators, enables the detection of very small precipitate volume fractions. We detected the standard C14 hcp Zr(Cr,Fe)2 precipitates, (the stable second phase in Zircaloy-4) in the bulk material at a cumulative annealing parameter as low as 10-20 h, and we followed the kinetics of precipitation and growth as a function of the cumulative annealing parameter (CAP) in the range 10-22 (quench) to 10-16 h. In addition, the unique combination of spatial resolution and elemental sensitivity of the 2ID-D/E microbeam line at the Advanced Photon Source at Argonne (APS) allows study of the alloying element concentrations at ppm levels in an area as small as 0.2 mm. We used x-ray fluorescence induced by this sub-micron x-ray beam to determine the concentration of these alloying elements in the matrix as a function of alloy type and thermal history. We discuss these results and the potential of synchrotron radiation-based techniques for studying zirconium alloys

  5. Advanced Turbine Systems (ATS). Phase 1: System scoping and feasibility studies

    Science.gov (United States)

    White, D. J.

    1993-04-01

    As part of this involvement, Solar intends to design and commercialize a unique gas turbine system that promises high cycle efficiencies and low exhaust emissions. This engine of approximately 12-MW will be targeted for the dispersed power markets both urban and rural. Goals of 50% thermal efficiency and 8 parts-per-million by volume (ppmv) nitrogen oxide emissions were established. Reliability, availability, and maintainability (RAM) will continue to be the most important factors in the competitive marketplace. The other major goal adopted was one of reducing the cost of power produced by 10%. This reduction is based on the cost of power (COP) associated with today's engines that lie in the same horsepower range as that targeted in this study. An advanced cycle based on an approximation of the Ericsson Cycle was adopted after careful studies of a number of different cycles. This advanced intercooled, recuperated engine when fired at 2450 F will be capable of meeting the 50% efficiency goal if the cooling air requirements do not exceed 7% of the total air flow rate. This latter qualification will probably dictate the use of ceramic parts for both the nozzle guide vanes and the turbine blades. Cooling of these parts will probably be required and the 7% cooling flow allowance is thought to be adequate for such materials. Analyses of the cost of power and RAM goals show that the installed cost of this advanced engine can be approximately 50% above today's costs. This cost is based on $4.00 per million Btu fuel and a COP reduction of 10% while maintaining the same RAM as today's engines.

  6. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    Science.gov (United States)

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  7. Nanoencapsulation of phase change materials for advanced thermal energy storage systems

    Science.gov (United States)

    Shchukina, E. M.; Graham, M.; Zheng, Z.

    2018-01-01

    Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, which can be used at times of peak demand; and to reduce overall energy demand through passive thermal regulation. 198.3 million tons of oil equivalent were used in the EU in 2013 for heating. However, bulk PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits such as protection of the PCM from the external environment and increased specific surface area to improve heat transfer. This review highlights techniques for the encapsulation of both organic and inorganic PCMs, paying particular attention to nanoencapsulation (capsules with sizes energy release/uptake. PMID:29658558

  8. Nanoencapsulation of phase change materials for advanced thermal energy storage systems.

    Science.gov (United States)

    Shchukina, E M; Graham, M; Zheng, Z; Shchukin, D G

    2018-04-16

    Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, which can be used at times of peak demand; and to reduce overall energy demand through passive thermal regulation. 198.3 million tons of oil equivalent were used in the EU in 2013 for heating. However, bulk PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits such as protection of the PCM from the external environment and increased specific surface area to improve heat transfer. This review highlights techniques for the encapsulation of both organic and inorganic PCMs, paying particular attention to nanoencapsulation (capsules with sizes energy release/uptake.

  9. Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus. Nine Japanese institutions trial

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kaoru [Iwate Medical Univ., Morioka (Japan). School of Medicine; Iizuka, Toshifumi; Ando, Nobutoshi; Ide, Hiroko

    1996-10-01

    A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1{sub (LYM)}), were enrolled in the study for treatment with cisplatin (70 mg/m{sup 2}) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m{sup 2}) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer. (author)

  10. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study

    Science.gov (United States)

    Strumberg, D; Scheulen, M E; Schultheis, B; Richly, H; Frost, A; Büchert, M; Christensen, O; Jeffers, M; Heinig, R; Boix, O; Mross, K

    2012-01-01

    Background: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). Methods: Patients received oral regorafenib 60–220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. Results: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0–7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7–280 days). The most common treatment-related toxicities included hand–foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66–161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. Conclusion: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population. PMID:22568966

  11. Advanced phase change materials and systems for solar passive heating and cooling of residential buildings

    Energy Technology Data Exchange (ETDEWEB)

    Salyer, I.O.; Sircar, A.K.; Dantiki, S.

    1988-01-01

    During the last three years under the sponsorship of the DOE Solar Passive Division, the University of Dayton Research Institute (UDRI) has investigated four phase change material (PCM) systems for utility in thermal energy storage for solar passive heating and cooling applications. From this research on the basis of cost, performance, containment, and environmental acceptability, we have selected as our current and most promising series of candidate phase change materials, C-15 to C-24 linear crystalline alkyl hydrocarbons. The major part of the research during this contract period was directed toward the following three objectives. Find, test, and develop low-cost effective phase change materials (PCM) that melt and freeze sharply in the comfort temperature range of 73--77{degree}F for use in solar passive heating and cooling of buildings. Define practical materials and processes for fire retarding plasterboard/PCM building products. Develop cost-effective methods for incorporating PCM into building construction materials (concrete, plasterboard, etc.) which will lead to the commercial manufacture and sale of PCM-containing products resulting in significant energy conservation.

  12. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

    Directory of Open Access Journals (Sweden)

    Ping Fang

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

  13. Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations

    NARCIS (Netherlands)

    Zimmer, Lisa; Barlesi, Fabrice; Martinez-Garcia, Maria; Dieras, Veronique; Schellens, Jan H M; Spano, Jean-Philippe; Middleton, Mark R; Calvo, Emiliano; Paz-Ares, Luiz; Larkin, James; Pacey, Simon; Venturi, Miro; Kraeber-Bodéré, Françoise; Tessier, Jean J L; Eberhardt, Wilfried Ernst Erich; Paques, Michel; Guarin, Ernesto; Meresse, Valerie; Soria, Jean-Charles

    2014-01-01

    PURPOSE: This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN: We undertook a multicenter phase I two-part study (dose escalation and cohort expansion).

  14. Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation

    NARCIS (Netherlands)

    Millot, F; Guilhot, J; Nelken, B; Leblanc, T; De Bont, ES; Bekassy, AN; Gadner, H; Sufliarska, S; Stary, J; Gschaidmeier, H; Guilhot, F; Suttorp, M

    A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In

  15. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  16. A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

    Science.gov (United States)

    Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

    2010-07-01

    Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

  17. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Patrinee, Traisathit; Gestel, Dirk Van

    2015-01-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose-volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm 3 (30.5%) and 5.4 cm 3 (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6-5.9 Gy, P < 0.001 and 2.1-9.9 Gy, P < 0.001, respectively). The D mean of the contralateral parotid decreased in 70% of the patients (range, 0.2-4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC. (author)

  18. A phase Ib study of everolimus combined with metformin for patients with advanced cancer.

    Science.gov (United States)

    Molenaar, Remco J; van de Venne, Tim; Weterman, Mariëtte J; Mathot, Ron A; Klümpen, Heinz-Josef; Richel, Dick J; Wilmink, Johanna W

    2018-02-01

    Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. At the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 out of 5 patients experienced a DLT. After de-escalation to 5 mg everolimus qd and 500 mg metformin bid, considerable toxicity was still observed and patient enrollment was terminated. In pharmacokinetic analyses, metformin was eliminated slower when co-administered with everolimus than as single-agent. After 9 weeks of treatment, 3 patients were still on study and all had stable disease. Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides.

  19. Advanced supersonic propulsion study, phase 2. [propulsion system performance, design analysis and technology assessment

    Science.gov (United States)

    Howlett, R. A.

    1975-01-01

    A continuation of the NASA/P and WA study to evaluate various types of propulsion systems for advanced commercial supersonic transports has resulted in the identification of two very promising engine concepts. They are the Variable Stream Control Engine which provides independent temperature and velocity control for two coannular exhaust streams, and a derivative of this engine, a Variable Cycle Engine that employs a rear flow-inverter valve to vary the bypass ratio of the cycle. Both concepts are based on advanced engine technology and have the potential for significant improvements in jet noise, exhaust emissions and economic characteristics relative to current technology supersonic engines. Extensive research and technology programs are required in several critical areas that are unique to these supersonic Variable Cycle Engines to realize these potential improvements. Parametric cycle and integration studies of conventional and Variable Cycle Engines are reviewed, features of the two most promising engine concepts are described, and critical technology requirements and required programs are summarized.

  20. Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D.; Dinkel, Julien; Herfarth, Klaus K.; Schubert, Kai; Eichbaum, Michael H.; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-01-01

    Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  1. Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

    Science.gov (United States)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D; Dinkel, Julien; Herfarth, Klaus K; Schubert, Kai; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-04-01

    To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  2. HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Shi-Ming; Lu, Sheng-Nan; Chen, Ping-Tsung; Jeng, Long-Bin; Chen, Shinn-Cherng; Hu, Chi-Tan; Yang, Sien-Sing; Le Berre, Marie-Aude; Liu, Xuan; Mitchell, David Y; Prins, Klaas; Grevel, Joachim; Peña, Carol A E; Meinhardt, Gerold

    2017-03-01

    Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients. The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively. There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.

  3. Advanced numerical methods for three dimensional two-phase flow calculations

    Energy Technology Data Exchange (ETDEWEB)

    Toumi, I. [Laboratoire d`Etudes Thermiques des Reacteurs, Gif sur Yvette (France); Caruge, D. [Institut de Protection et de Surete Nucleaire, Fontenay aux Roses (France)

    1997-07-01

    This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe`s method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations.

  4. Advanced numerical methods for three dimensional two-phase flow calculations

    International Nuclear Information System (INIS)

    Toumi, I.; Caruge, D.

    1997-01-01

    This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe's method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations

  5. Effects of hard mask etch on final topography of advanced phase shift masks

    Science.gov (United States)

    Hortenbach, Olga; Rolff, Haiko; Lajn, Alexander; Baessler, Martin

    2017-07-01

    Continuous shrinking of the semiconductor device dimensions demands steady improvements of the lithographic resolution on wafer level. These requirements challenge the photomask industry to further improve the mask quality in all relevant printing characteristics. In this paper topography of the Phase Shift Masks (PSM) was investigated. Effects of hard mask etch on phase shift uniformity and mask absorber profile were studied. Design of experiments method (DoE) was used for the process optimization, whereas gas composition, bias power of the hard mask main etch and bias power of the over-etch were varied. In addition, influence of the over-etch time was examined at the end of the experiment. Absorber depth uniformity, sidewall angle (SWA), reactive ion etch lag (RIE lag) and through pitch (TP) dependence were analyzed. Measurements were performed by means of Atomic-force microscopy (AFM) using critical dimension (CD) mode with a boot-shaped tip. Scanning electron microscope (SEM) cross-section images were prepared to verify the profile quality. Finally CD analysis was performed to confirm the optimal etch conditions. Significant dependence of the absorber SWA on hard mask (HM) etch conditions was observed revealing an improvement potential for the mask absorber profile. It was found that hard mask etch can leave a depth footprint in the absorber layer. Thus, the etch depth uniformity of hard mask etch is crucial for achieving a uniform phase shift over the active mask area. The optimized hard mask etch process results in significantly improved mask topography without deterioration of tight CD specifications.

  6. Advanced Start of Combustion Sensor Phases I and II-A: Feasibility Demonstration, Design and Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Chad Smutzer

    2010-01-31

    Homogeneous Compressed Charge Ignition (HCCI) has elevated the need for Start of Combustion (SOC) sensors. HCCI engines have been the exciting focus of engine research recently, primarily because HCCI offers higher thermal efficiency than the conventional Spark Ignition (SI) engines and significantly lower NOx and soot emissions than conventional Compression Ignition (CI) engines, and could be fuel neutral. HCCI has the potential to unify all the internal combustion engine technology to achieve the high-efficiency, low-emission goal. However, these advantages do not come easy. It is well known that the problems encountered with HCCI combustion center on the difficulty of controlling the Start of Combustion. TIAX has an SOC sensor under development which has shown promise. In previous work, including a DOE-sponsored SBIR project, TIAX has developed an accelerometer-based method which was able to determine SOC within a few degrees crank angle for a range of operating conditions. A signal processing protocol allows reconstruction of the combustion pressure event signal imbedded in the background engine vibration recorded by the accelerometer. From this reconstructed pressure trace, an algorithm locates the SOC. This SOC sensor approach is nonintrusive, rugged, and is particularly robust when the pressure event is strong relative to background engine vibration (at medium to high engine load). Phase I of this project refined the previously developed technology with an engine-generic and robust algorithm. The objective of the Phase I research was to answer two fundamental questions: Can the accelerometer-based SOC sensor provide adequate SOC event capture to control an HCCI engine in a feedback loop? And, will the sensor system meet cost, durability, and software efficiency (speed) targets? Based upon the results, the answer to both questions was 'YES'. The objective of Phase II-A was to complete the parameter optimization of the SOC sensor prototype in order

  7. SPIRIT trial: A phase III pragmatic trial of an advance care planning intervention in ESRD.

    Science.gov (United States)

    Song, Mi-Kyung; Unruh, Mark L; Manatunga, Amita; Plantinga, Laura C; Lea, Janice; Jhamb, Manisha; Kshirsagar, Abhijit V; Ward, Sandra E

    2018-01-01

    Advance care planning (ACP) is a central tenet of dialysis care, but the vast majority of dialysis patients report never engaging in ACP discussions with their care providers. Over the last decade, we have developed and iteratively tested SPIRIT (Sharing Patient's Illness Representation to Increase Trust), a theory-based, patient- and family-centered advance care planning intervention. SPIRIT is a six-step, two-session, face-to-face intervention to promote cognitive and emotional preparation for end-of-life decision making for patients with ESRD and their surrogates. In these explanatory trials, SPIRIT was delivered by trained research nurses. Findings consistently revealed that patients and surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, and surrogates in SPIRIT reported significantly improved post-bereavement psychological outcomes after the patient's death compared to a no treatment comparison condition. As a critical next step, we are conducting an effectiveness-implementation study. This study is a multicenter, clinic-level cluster randomized pragmatic trial to evaluate the effectiveness of SPIRIT delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics, compared to usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, including sustainability. We will recruit 400 dyads of patients at high risk of death in the next year and their surrogates from 30 dialysis clinics in four states. This trial of SPIRIT will generate novel, meaningful insights about improving ACP in dialysis care. ClinicalTrials.govNCT03138564, registered 05/01/2017. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Advanced numerical methods for three dimensional two-phase flow calculations in PWR

    International Nuclear Information System (INIS)

    Toumi, I.; Gallo, D.; Royer, E.

    1997-01-01

    This paper is devoted to new numerical methods developed for three dimensional two-phase flow calculations. These methods are finite volume numerical methods. They are based on an extension of Roe's approximate Riemann solver to define convective fluxes versus mean cell quantities. To go forward in time, a linearized conservative implicit integrating step is used, together with a Newton iterative method. We also present here some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. This kind of numerical method, which is widely used for fluid dynamic calculations, is proved to be very efficient for the numerical solution to two-phase flow problems. This numerical method has been implemented for the three dimensional thermal-hydraulic code FLICA-4 which is mainly dedicated to core thermal-hydraulic transient and steady-state analysis. Hereafter, we will also find some results obtained for the EPR reactor running in a steady-state at 60% of nominal power with 3 pumps out of 4, and a thermal-hydraulic core analysis for a 1300 MW PWR at low flow steam-line-break conditions. (author)

  9. A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

    Science.gov (United States)

    Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T; Kummar, Shivaani; Hansen, Aaron R; Siu, Lillian L; Piekarz, Richard L; Sukari, Ammar W; Chao, Joseph; Pilat, Mary Jo; Smith, Daryn W; Casetta, Lindsay; Boerner, Scott A; Chen, Alice; Lenkiewicz, Elizabeth; Malasi, Smriti; LoRusso, Patricia M

    2017-05-16

    Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Thirty patients were enrolled. Median age of patients was 53 years (range 21-73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.

  10. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  12. An advanced three-phase physical, experimental and numerical method for tsunami induced boulder transport

    Science.gov (United States)

    Oetjen, Jan; Engel, Max; Prasad Pudasaini, Shiva; Schüttrumpf, Holger; Brückner, Helmut

    2017-04-01

    Coasts around the world are affected by high-energy wave events like storm surges or tsunamis depending on their regional climatological and geological settings. By focusing on tsunami impacts, we combine the abilities and experiences of different scientific fields aiming at improved insights of near- and onshore tsunami hydrodynamics. We investigate the transport of coarse clasts - so called boulders - due to tsunami impacts by a multi-methodology approach of numerical modelling, laboratory experiments, and sedimentary field records. Coupled numerical hydrodynamic and boulder transport models (BTM) are widely applied for analysing the impact characteristics of the transport by tsunami, such as wave height and flow velocity. Numerical models able to simulate past tsunami events and the corresponding boulder transport patterns with high accuracy and acceptable computational effort can be utilized as powerful forecasting models predicting the impact of a coast approaching tsunami. We have conducted small-scale physical experiments in the tilting flume with real shaped boulder models. Utilizing the structure from motion technique (Westoby et al., 2012) we reconstructed real boulders from a field study on the Island of Bonaire (Lesser Antilles, Caribbean Sea, Engel & May, 2012). The obtained three-dimensional boulder meshes are utilized for creating downscaled replica of the real boulder for physical experiments. The results of the irregular shaped boulder are compared to experiments with regular shaped boulder models to achieve a better insight about the shape related influence on transport patterns. The numerical model is based on the general two-phase mass flow model by Pudasaini (2012) enhanced for boulder transport simulations. The boulder is implemented using the immersed boundary technique (Peskin, 2002) and the direct forcing approach. In this method Cartesian grids (fluid and particle phase) and Lagrangian meshes (boulder) are combined. By applying the

  13. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    International Nuclear Information System (INIS)

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-01-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation

  14. Exploitation of Digital Filters to Advance the Single-Phase T/4 Delay PLL System

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

    2016-01-01

    will violate this design rule and it can become a major challenge for digital controllers. To deal with the above issue, this paper first exploits a virtual unit delay (z_v^-1) to emulate the viable sampling behavior in practical digital signal processors with a fixed sampling rate. This exploitation......With the development of digital signal processing technologies, control and monitoring of power electronics conversion systems have been evolving to become fully digital. As the basic element in the design and analysis phase of digital controllers or filters, a number of unit delays (z^-1) have...... been employed, e.g., in a cascaded structure. Practically, the number of unit delays is designed as an integer, which is related to the sampling frequency (e.g., 50 Hz). More common, the sampling frequency is fixed during operation for simplicity and design. Hence, any disturbance in the ac signal...

  15. Advances in simulating non-congruent phase transitions of hyperstoichiometric uranium dioxide fuel

    International Nuclear Information System (INIS)

    Welland, M.J.; Thompson, W.T.; Lewis, B.J.

    2007-01-01

    A model is being developed to simulate UO 2 at very high temperatures incorporating the effects of non-congruent phase transitions. In particular, the melting transformation and the possible 'Λ-transition' is being investigated to help support the design and analysis of experimental work being conducted as part of nuclear safety research. This work includes the interpretation of the behaviour of operating CANDU fuel under upset conditions, where centerline melting may potentially occur (particularly if the fuel is oxidized). The model presented here numerically solves a system of coupled nonlinear differential equations as derived from fundamental principles. The results of the model present here compare well against laser flash experiments in recently published literature. (author)

  16. Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial.

    Science.gov (United States)

    D'Agnolo, Hedwig M A; Kievit, Wietske; Takkenberg, R Bart; Riaño, Ioana; Bujanda, Luis; Neijenhuis, Myrte K; Brunenberg, Ellen J L; Beuers, Ulrich; Banales, Jesus M; Drenth, Joost P H

    2016-09-01

    Ursodeoxycholic acid (UDCA) inhibits proliferation of polycystic human cholangiocytes in vitro and hepatic cystogenesis in a rat model of polycystic liver disease (PLD) in vivo. Our aim was to test whether UDCA may beneficially affect liver volume in patients with advanced PLD. We conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500ml were randomly assigned to UDCA treatment (15-20mg/kg/day) for 24weeks, or to no treatment. Primary endpoint was proportional change in TLV. Secondary endpoints were change in symptoms and health-related quality of life. We performed a post-hoc analysis of the effect of UDCA on liver cyst volume (LCV). We included 34 patients and were able to assess primary endpoint in 32 patients, 16 with autosomal dominant polycystic kidney disease (ADPKD) and 16 with autosomal dominant polycystic liver disease (ADPLD). Proportional TLV increased by 4.6±7.7% (mean TLV increased from 6697ml to 6954ml) after 24weeks of UDCA treatment compared to 3.1±3.8% (mean TLV increased from 5512ml to 5724ml) in the control group (p=0.493). LCV was not different after 24weeks between controls and UDCA treated patients (p=0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p=0.049). UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKD patients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment. Current therapies for polycystic liver disease are invasive and have high recurrence risks. Our trial showed that the drug, ursodeoxycholic acid, was not able to reduce liver volume in patients with polycystic liver disease. However, a subgroup analysis in patients that have kidney cysts as well showed that liver cyst volume growth was reduced in patients who received ursodeoxycholic acid in comparison

  17. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING PHASE 3 RESTRUCTURED (3R); TOPICAL

    International Nuclear Information System (INIS)

    Unknown

    1999-01-01

    In the early 90's GE recognized the need to introduce new technology to follow on to the ''F'' technology the Company introduced in 1988. By working with industry and DOE, GE helped shape the ATS program goal of demonstrating a gas turbine, combined-cycle system using natural gas as the primary fuel that achieves the following targets: system efficiency exceeding 60% lower heating value basis; environmental superiority under full-load operating conditions without the use of post-combustion emissions controls, environmental superiority includes limiting NO(sub 2) to less than 10 parts per mission by volume (dry basis) at 15% oxygen; busbar energy costs that are 10% less than current state-of-the-art turbine systems meeting the same environmental requirements; fuel-flexible designs operating on natural gas but also capable of being adapted to operate on coal-based, distillate, or biomass fuels; reliability-availability-maintainability (RAM) that is equivalent to modern advanced power generation systems; and commercial systems that could enter the market in the year 2000

  18. A phase I study of concurrent chemoradiotherapy and cetuximab for locally advanced esophageal cancer

    DEFF Research Database (Denmark)

    Holländer, Cecilie; Baeksgaard, Lene; Sorensen, Morten

    2012-01-01

    AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of concurrent chemoradiotherapy and cetuximab in patients with non-resectable locally advanced esophageal cancer. PATIENTS AND METHODS: Escalating doses of oxaliplatin every second week and daily tegafur....../uracil were given concurrently with radiotherapy, 59.4 Gy in 33 fractions. Cetuximab was given on day 15 (400 mg/m(2)) and weekly (250 mg/m(2)) during radiotherapy. Fixed doses of oxaliplatin (130 mg/m(2)) and tegafur/uracil (300 mg/m(2)) were administered before, and after radiotherapy. RESULTS: Eleven...... patients were included in the study; two were excluded due to allergic reactions to cetuximab. In DL2 (tegafur/uracil 300 mg/m(2), oxaliplatin 30 mg/m(2)) two grade 3/4 fistula and one grade 3 neuropathy were observed. Six patients were enrolled in DL1 (tegafur/uracil 150 mg/m(2)/, oxaliplatin 30 mg/m(2...

  19. Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

    Science.gov (United States)

    Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

    1990-02-28

    Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

  20. Investigations of the reflood-phase after a loss-of-coolant-accident of an advanced pressurized water reactor (APWR)

    International Nuclear Information System (INIS)

    Schumann, S.; Oldekop, W.

    1983-01-01

    Differences between a high converting advanced pressurized-water reactor (APWR) and a conventional PWR, which are relevant to the reflood-phase after LOCA are presented. The used code and its verification by PWR-reflood experiments is explained. Comparative calculations for APWR and PWR with several conservative assumptions for example cold-leg-injection only, yield nearly the same maximum midplane-temperatures for the average-channel. For the APWR, however, the upper half of the rod shows higher temperatures. Quenchfront and core-water-level increase more slowly. The differences in the reflood-thermohydraulics are analysed in detail. A conservative hot-channel calculation shows maximum temperatures of about 920 0 C. Finally the influence of conservative assumptions is described and the necessity of experiments pointed out. (orig.)

  1. Gender differences on the job satisfaction in the phase of implementing advanced manufacturing technology in the Chinese manufacturing firms.

    Science.gov (United States)

    Yu, Na; Shen, Li Ming; Lewark, Siegfried

    2012-01-01

    This research gave an effort to study on gender differences in the job satisfaction for technological innovation at Chinese manufacturing firm. The exploratory study was conducted in four Chinese furniture manufacturing firms, which are all in the phases of introducing advanced manufacturing system. The results of statistical analysis show that general satisfaction of female employees to their jobs is significantly higher than male employees. In addition, supervisory satisfaction of female employees is significantly higher than male employees. The findings of the study reveal that activities are suggested to be carried out to increase the job satisfaction of male employees, especially improve communication and relationship between the managerial and the non-managerial levels in the innovation process. In addition, the higher job satisfaction of female employees could be considered a positive factor for the successful implementation of AMT in the technological innovation, although male employees are still dominated work force in the case study firms.

  2. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Wen, E-mail: sjfchiou@gmail.com [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Lin, Li-Ching [Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Kuo, Yu-Cheng [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Kuo, Chia-Chun [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Chiou, Jeng-Fong [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  3. Capecitabine, oxaliplatin and radiotherapy: Results of the phase II study in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Torres, M.

    2010-01-01

    Objectives: usufruct ing the benefits of preoperative adjuvant (biological, functional, surgical, etc.), a phase II essay whose purpose was to evaluate the response and toxicity activated preoperative concomitant radio chemotherapy in the oncological pathology. Material and Methods: Between 01.01.03 and 31.12.09 64 consecutive patients were treated with rectal cancer and histopathology for adenocarcinoma; none of them had been received previous oncological treatment and did not have a second simultaneous neoplasia. The age of the patients had a range between 38 and 69 years with a mean of 57.3 years; 60% belonged to male and according to ECOG performance status was 0≤2. All tumors were at a distance of 12cms ≤ anal margin and were staged as AJCC allowing recruiting 28 patients in stage II (T3, T4) and 36 patients in stage III (N1, N2). Staging was performed with clinical (general and proctologic examination), fibrocolonoscopy, systemic imaging and local (TAC, EER, MRI) and laboratory (CEA) total pelvic X 18 MV photons was irradiated by ICRU-50 in a normo fractionation with daily fractions of 1.8 Gy to a final dose of 45 Gy in 25 sessions using multiple fields (box technique) .The chemotherapy was administered Capecitabine 825mgr / m2 / day in 2 daily doses during the course of radiotherapy and oxaliplatin 50mgr / m2 on days 1, 8, 15, 22 and 29 of the same therapy. All patients underwent surgery between 4 and 8 weeks after completing the coincidence. Follow-up it was full and the response was weighted according to the degree of tumor regression (GRT) of Dworak and Toxicity was graded according to RTOG / EORTC. Results: As the TSO the following pathological responses were obtained: GRT 0 (remission Full), 16% GRT 1 and 2 (moderate and low remission), 55% and TSO 3 and 4 (weak or absent remission) 29%. Although there were no deaths therapy, toxicity was severe and frequent with 30% Grade 3 and 4 (skin, gastrointestinal, hematological, neuropathies and

  4. Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J.A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    Purpose In phase I/II trials, the cytotoxic T lymphocyte–associated antigen-4–blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma. PMID:23295794

  5. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-02-10

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

  6. Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

    Directory of Open Access Journals (Sweden)

    Savage Paul

    2002-05-01

    Full Text Available Abstract Background 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. Methods Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. Results The median age was 64 yrs (34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. Conclusions This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin are in progress and may prove encouraging.

  7. Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Cardin, Dana B; Goff, Laura; Li, Chung-I; Shyr, Yu; Winkler, Charles; DeVore, Russell; Schlabach, Larry; Holloway, Melanie; McClanahan, Pam; Meyer, Krista; Grigorieva, Julia; Berlin, Jordan; Chan, Emily

    2014-01-01

    This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32–0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat “Good” patients had superior PFS (HR = 0.18, 95% CI: 0.06–0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13–0.77, P = 0.008) compared to VeriStrat “Poor” patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies

  8. The scrounge-atron: a phased approach to the advanced hydrotest facility utilizing proton radiography

    International Nuclear Information System (INIS)

    Alford, O.J.; Barnes, P.D. Jr.; Chargin, A.K.; Dekin, W.D.; Hartouni, E.P.; Hockman, J.; Hockman, J.N.; Ladran, A.S.; Libkind, M.A.; Moore, T.L.; Ohnuma, S.; Pastrnak, J.W.; Pico, R.E.; Ruggiero, A.G.; Souza, R.J.; Stoner, J.M.; Wilson, J.H.

    1999-01-01

    The Department of Energy has initiated its Stockpile Stewardship and Management Program (SSMP) to provide a single, integrated technical program for maintaining the continued safety and reliability of the nation's nuclear weapons stockpile in the absence of nuclear testing. Consistent with the SSMP, the Advanced Hydrotest Facility (AHF) has been conceived to provide improved radiographic imaging with multiple axes and multiple time frames. The AHF would be used to better understand the evolution of nuclear weapon primary implosion shape under normal and accident scenarios. There are three fundamental technologies currently under consideration for use on the AHF. These include linear induction acceleration, inductive-adder pulsed-power technology (both technologies using high current electron beams to produce an intense X-ray beam) and high-energy proton accelerators to produce a proton beam. The Scrounge-atron (a proton synchrotron) was conceived to be a relatively low cost demonstration of the viability of the third technology using bursts of energetic protons, magnetic lenses, and particle detectors to produce the radiographic image. In order for the Scrounge-atron to provide information useful for the AHF technology decision, the accelerator would have to be built as quickly and as economically as possible. These conditions can be met by scrounging parts from decommissioned accelerators across the country, especially the Main Ring at Fermilab. The Scrounge-atron is designed to meet the baseline parameters for single axis proton radiography: a 20 GeV proton beam of ten pulses, 10 11 protons each, spaced 250 ns apart

  9. Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Fouchardiere, Christelle de la; Negrier, Sylvie; Labrosse, Hugues; Martel Lafay, Isabelle; Desseigne, Francoise; Meeus, Pierre; Tavan, David; Petit-Laurent, Fabien; Rivoire, Michel; Perol, David; Carrie, Christian

    2010-01-01

    Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m 2 per day and then escalated by increments of 2 mg/m 2 every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m 2 to 20 mg/m 2 per day). The maximum tolerated dose was determined to be 18 mg/m 2 per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m 2 per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.

  10. Phase Equilibrium and Austenite Decomposition in Advanced High-Strength Medium-Mn Bainitic Steels

    Directory of Open Access Journals (Sweden)

    Adam Grajcar

    2016-10-01

    Full Text Available The work addresses the phase equilibrium analysis and austenite decomposition of two Nb-microalloyed medium-Mn steels containing 3% and 5% Mn. The pseudobinary Fe-C diagrams of the steels were calculated using Thermo-Calc. Thermodynamic calculations of the volume fraction evolution of microstructural constituents vs. temperature were carried out. The study comprised the determination of the time-temperature-transformation (TTT diagrams and continuous cooling transformation (CCT diagrams of the investigated steels. The diagrams were used to determine continuous and isothermal cooling paths suitable for production of bainite-based steels. It was found that the various Mn content strongly influences the hardenability of the steels and hence the austenite decomposition during cooling. The knowledge of CCT diagrams and the analysis of experimental dilatometric curves enabled to produce bainite-austenite mixtures in the thermomechanical simulator. Light microscopy (LM, scanning electron microscopy (SEM, and transmission electron microscopy (TEM were used to assess the effect of heat treatment on morphological details of produced multiphase microstructures.

  11. Investigation of vertical slug flow with advanced two-phase flow instrumentation

    International Nuclear Information System (INIS)

    Mi, Y.; Ishii, M.; Tsoukalas, L.H.

    2001-01-01

    Extensive experiments of vertical slug flow were carried out with an electromagnetic flowmeter and an impedance void-meter in an air-water two-phase experimental loop. The basic principles of these instruments in vertical slug flow measurements are discussed. Time series of the liquid velocity and the impedance were separated into two parts corresponding to the Taylor bubble and the liquid slug. Characteristics of slug flow, such as the void fractions, probabilities and lengths of the Taylor bubble and liquid slug, slug unit velocity, area-averaged liquid velocity, and liquid film velocity of the Taylor bubble tail, etc., were obtained. For the first time, the area-averaged liquid velocity of slug flow was revealed by the electromagnetic flowmeter. It is realized that the void fraction of the liquid slug is determined by the turbulent intensity due to the relative liquid motion between the Taylor bubble tail region and its wake region. A correlation of the void fraction of the liquid slug is developed based on experimental results obtained from a test section with 50.8 mm i.d. The results of this study suggest a promising improvement in understanding of vertical slug flow

  12. High-speed, low-damage grinding of advanced ceramics Phase 1. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, J.A. [Eaton Corp., Willoughby Hills, OH (United States). Mfg. Technologies Center; Malkin, S. [Univ. of Massachusetts (United States)

    1995-03-01

    In manufacture of structural ceramic components, grinding costs can comprise up to 80% of the entire manufacturing cost. Most of these costs arise from the conventional multi-step grinding process with numerous grinding wheels and additional capital equipment, perishable dressing tools, and labor. In an attempt to reduce structural ceramic grinding costs, a feasibility investigation was undertaken to develop a single step, roughing-finishing process suitable for producing high-quality silicon nitride ceramic parts at high material removal rates at lower cost than traditional, multi-stage grinding. This feasibility study employed combined use of laboratory grinding tests, mathematical grinding models, and characterization of resultant material surface condition. More specifically, this Phase 1 final report provides a technical overview of High-Speed, Low-Damage (HSLD) ceramic grinding and the conditions necessary to achieve the small grain depths of cut necessary for low damage grinding while operating at relatively high material removal rates. Particular issues addressed include determining effects of wheel speed and material removal rate on resulting mode of material removal (ductile or brittle fracture), limiting grinding forces, calculation of approximate grinding zone temperatures developed during HSLD grinding, and developing the experimental systems necessary for determining HSLD grinding energy partition relationships. In addition, practical considerations for production utilization of the HSLD process are also discussed.

  13. ADVANCED DIAGNOSTIC TECHNIQUES FOR THREE-PHASE SLURRY BUBBLE COLUMN REACTORS(SBCR)

    Energy Technology Data Exchange (ETDEWEB)

    M.H. Al-Dahhan; L.S. Fan; M.P. Dudukovic

    2002-07-25

    This report summarizes the accomplishment made during the third year of this cooperative research effort between Washington University, Ohio State University and Air Products and Chemicals. Data processing of the performed Computer Automated Radioactive Particle Tracking (CARPT) experiments in 6 inch column using air-water-glass beads (150 {micro}m) system has been completed. Experimental investigation of time averaged three phases distribution in air-Therminol LT-glass beads (150 {micro}m) system in 6 inch column has been executed. Data processing and analysis of all the performed Computed Tomography (CT) experiments have been completed, using the newly proposed CT/Overall gas holdup methodology. The hydrodynamics of air-Norpar 15-glass beads (150 {micro}m) have been investigated in 2 inch slurry bubble column using Dynamic Gas Disengagement (DGD), Pressure Drop fluctuations, and Fiber Optic Probe. To improve the design and scale-up of bubble column reactors, a correlation for overall gas holdup has been proposed based on Artificial Neural Network and Dimensional Analysis.

  14. Advanced Laser-Based Techniques for Gas-Phase Diagnostics in Combustion and Aerospace Engineering.

    Science.gov (United States)

    Ehn, Andreas; Zhu, Jiajian; Li, Xuesong; Kiefer, Johannes

    2017-03-01

    Gaining information of species, temperature, and velocity distributions in turbulent combustion and high-speed reactive flows is challenging, particularly for conducting measurements without influencing the experimental object itself. The use of optical and spectroscopic techniques, and in particular laser-based diagnostics, has shown outstanding abilities for performing non-intrusive in situ diagnostics. The development of instrumentation, such as robust lasers with high pulse energy, ultra-short pulse duration, and high repetition rate along with digitized cameras exhibiting high sensitivity, large dynamic range, and frame rates on the order of MHz, has opened up for temporally and spatially resolved volumetric measurements of extreme dynamics and complexities. The aim of this article is to present selected important laser-based techniques for gas-phase diagnostics focusing on their applications in combustion and aerospace engineering. Applicable laser-based techniques for investigations of turbulent flows and combustion such as planar laser-induced fluorescence, Raman and Rayleigh scattering, coherent anti-Stokes Raman scattering, laser-induced grating scattering, particle image velocimetry, laser Doppler anemometry, and tomographic imaging are reviewed and described with some background physics. In addition, demands on instrumentation are further discussed to give insight in the possibilities that are offered by laser flow diagnostics.

  15. Advances on the time differential three-phase-lag heat conduction model and major open issues

    Science.gov (United States)

    D'Apice, Ciro; Zampoli, Vittorio

    2017-07-01

    The main purpose of this short contribution is to summarize the recent achievements concerning the so-called time differential three-phase-lag heat conduction model, contextually focusing attention on some of the numerous open problems associated with such an attractive theory. After having briefly recalled the origin of the model at issue, the restrictions upon the delay times and the constitutive tensors able to make it thermodynamically consistent are recalled. Under these hypotheses, the investigation of the well-posedness issue has already provided important results in terms of uniqueness and continuous dependence of the solutions (even related to the thermoelastic case), as well as in terms of existence of a domain of influence of the assigned data in connection with the thermoelastic model. Finally, some of the main problems currently object of investigation are recalled, including the very challenging issues about the different possible choices of Taylor series expansion orders for the constitutive equation, the interaction of the model with energy processes that take place on the nanoscale, with multi-porous materials and with biological systems.

  16. Advanced far infrared blocked impurity band detectors based on germanium liquid phase epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Christopher Sean [Univ. of California, Berkeley, CA (United States)

    1998-05-01

    This research has shown that epilayers with residual impurity concentrations of 5 x 1013 cm-3 can be grown by producing the purest Pb available in the world. These epilayers have extremely low minority acceptor concentrations, which is ideal for fabrication of IR absorbing layers. The Pb LPE growth of Ge also has the advantageous property of gettering Cu from the epilayer and the substrate. Epilayers have been grown with intentional Sb doping for IR absorption on lightly doped substrates. This research has proven that properly working Ge BIB detectors can be fabricated from the liquid phase as long as pure enough solvents are available. The detectors have responded at proper wavelengths when reversed biased even though the response did not quite reach minimum wavenumbers. Optimization of the Sb doping concentration should further decrease the photoionization energy of these detectors. Ge BIB detectors have been fabricated that respond to 60 cm-1 with low responsivity. Through reduction of the minority residual impurities, detector performance has reached responsivities of 1 A/W. These detectors have exhibited quantum efficiency and NEP values that rival conventional photoconductors and are expected to provide a much more sensitive tool for new scientific discoveries in a number of fields, including solid state studies, astronomy, and cosmology.

  17. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    International Nuclear Information System (INIS)

    Geara, Fady B; Shamseddine, Ali; Khalil, Ali; Abboud, Mirna; Charafeddine, Maya; Seoud, Muhieddine

    2010-01-01

    This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m 2 Cisplatin (group I; 16 patients) or 50 mg/m 2 paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months. Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix

  18. Phase II trial of cisplatin in advanced or recurrent cancer of the vagina: a Gynecologic Oncology Group Study.

    Science.gov (United States)

    Thigpen, J T; Blessing, J A; Homesley, H D; Berek, J S; Creasman, W T

    1986-01-01

    Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.

  19. First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Barry H. Smith

    2016-01-01

    Full Text Available Purpose Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival, which is the secondary objective. Methods Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075. Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. Results RMBs were well tolerated at both dose levels (mean 660.9 per implant. AEs were (Grade 1/2 with no treatment-related SAEs. Conclusion The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

  20. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas

    International Nuclear Information System (INIS)

    Medina, Jose Antonio; Rueda, Antonio; Sacchetti de Pasos, Antonio; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asuncion; Alba, Emilio

    2006-01-01

    Background and purpose: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. Material and methods: A total of 94 patients (median age, 58 years) with UICC stage III (n=19) and IV (n=75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m 2 weekly, for the first 4 weeks. Results: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Conclusions: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data

  1. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Blake, Mónika; Mata-Moya, María Dolores de la; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

    2014-01-01

    Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

  2. Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)

    International Nuclear Information System (INIS)

    Lindemann, Kristina; Nordstrøm, Britta; Malander, Susanne; Christensen, Rene D; Mirza, Mansoor R; Kristensen, Gunnar B; Aavall-Lundqvist, Elisabeth; Vergote, Ignace; Rosenberg, Per; Boman, Karin

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients. Trial identification number (Clinical Trials.gov): http://www.clinicaltrials.gov/NCT01965080. Nordic Society of Gynecological Oncology: NSGO–EC–0302. EudraCT number: 2004-001103-35

  3. Delayed radionecrosis of the cerebral hemispheres following betatron electron beam irradiation for scalp cancer. Pathological and clinical findings in one case

    International Nuclear Information System (INIS)

    Buge, A.; Escourolle, R.; Rancurel, G.; Gray, F.; Pertuiset, B.F.

    1979-01-01

    Three years following an irradiation by the Betatron's electron beam of an epithelioma in left parieto occipital area of the scalp in a female patient aged 77, early suffering from high blood pressure, a fatal pseudo-tumoral brain necrosis occurs presenting as a rapidly increasing from of Wernicke's aphasia. The necropsy shows intense radionecrosis lesions of the brain and the bone, free of any parenchymatous malignant proliferation note-wortly for the striking density of microvascular changes as previously described in radiation therapy. The case observed some years ago, allows to definite again the limits doses of the extracranial irradiations now estimated at 1760 rets. That is the 'Nominal Standard Dose' (NSD) measured by rets and taking into account the number of seances (N) and the duration of irradiation (T) which would be to take the place of 'the total dose' (D) (rads). These dosimetric criteria themselves must be adjusted to the age and the vascular features of each patient [fr

  4. Delayed radionecrosis of the cerebral hemispheres following betatron electron beam irradiation for scalp cancer. Pathological and clinical findings in one case

    Energy Technology Data Exchange (ETDEWEB)

    Buge, A; Escourolle, R; Rancurel, G; Gray, F; Pertuiset, B F [Clinique Neurologique de la Salpetriere, 75 - Paris (France)

    1979-01-01

    Three years following an irradiation by the Betatron's electron beam of an epithelioma in left parieto occipital area of the scalp in a female patient aged 77, early suffering from high blood pressure, a fatal pseudo-tumoral brain necrosis occurs presenting as a rapidly increasing from of Wernicke's aphasia. The necropsy shows intense radionecrosis lesions of the brain and the bone, free of any parenchymatous malignant proliferation note-wortly for the striking density of microvascular changes as previously described in radiation therapy. The case observed some years ago, allows to definite again the limits doses of the extracranial irradiations now estimated at 1760 rets. That is the 'Nominal Standard Dose' (NSD) measured by rets and taking into account the number of seances (N) and the duration of irradiation (T) which would be to take the place of 'the total dose' (D) (rads). These dosimetric criteria themselves must be adjusted to the age and the vascular features of each patient.

  5. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

    Science.gov (United States)

    Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

    2009-05-01

    To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

  6. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

    Science.gov (United States)

    Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

    2015-06-01

    Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

  7. Brain-wave measures of workload in advanced cockpits: The transition of technology from laboratory to cockpit simulator, phase 2

    Science.gov (United States)

    Horst, Richard L.; Mahaffey, David L.; Munson, Robert C.

    1989-01-01

    The present Phase 2 small business innovation research study was designed to address issues related to scalp-recorded event-related potential (ERP) indices of mental workload and to transition this technology from the laboratory to cockpit simulator environments for use as a systems engineering tool. The project involved five main tasks: (1) Two laboratory studies confirmed the generality of the ERP indices of workload obtained in the Phase 1 study and revealed two additional ERP components related to workload. (2) A task analysis' of flight scenarios and pilot tasks in the Advanced Concepts Flight Simulator (ACFS) defined cockpit events (i.e., displays, messages, alarms) that would be expected to elicit ERPs related to workload. (3) Software was developed to support ERP data analysis. An existing ARD-proprietary package of ERP data analysis routines was upgraded, new graphics routines were developed to enhance interactive data analysis, and routines were developed to compare alternative single-trial analysis techniques using simulated ERP data. (4) Working in conjunction with NASA Langley research scientists and simulator engineers, preparations were made for an ACFS validation study of ERP measures of workload. (5) A design specification was developed for a general purpose, computerized, workload assessment system that can function in simulators such as the ACFS.

  8. Development of the advanced phased array UT technique for accurate sizing of cracks in the nozzle welding

    International Nuclear Information System (INIS)

    Nishida, Jun-ichiro; Kawanami, Seiichi; Ideo, Mitsushi; Matsuura, Takayuki; Chigusa, Naoki; Hirano, Shinro; Sera, Takehiko

    2010-01-01

    Recently, preventive maintenance tasks for welding of safe-end nozzles of reactor vessels and steam generators of PWRs in Japan had been carried out sequentially. Before the maintenance tasks, inspection services were carried out and several crack indications were found by eddy current testing (ECT). These indications were found in the welding which made by 600 series nickel base alloy and evaluated as stress corrosion cracks which were oriented to the axial direction of the nozzle. Then investigations to evaluate the depth of cracks were carried out by ultrasonic testing (UT) from inner surface of the nozzles. However they were difficult to evaluate the depth of cracks due to the high attenuation of the ultrasonic propagation caused by large grain structure of welding. And also it was required high resolution near surface region for accurate sizing. Therefore development of advanced phased array UT techniques specialized for the sizing at this portion was carried out. This paper reports the development status and verification test results. Firstly simulations of the ultrasonic propagation in the welding were carried out to optimize beam profiles of phased array probes. Next prototype probes were manufactured and verification tests were conducted to evaluate the accuracy of depth sizing. It is shown that the developed techniques have high sizing accuracy for artificial stress corrosion cracks in the welding. (author)

  9. Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

    International Nuclear Information System (INIS)

    Anthoney, D Alan; Miwa, Masanori; Twelves, Christopher; Evans, TRJ; Naik, Jay; MacPherson, Iain RJ; Crawford, Donna; Hartley, John M; Hartley, Janet A; Saito, Tomohisa; Abe, Masaichi; Jones, Keith

    2012-01-01

    A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m 2 . MTD was 10 mg/m 2 ; DLTs at 12 (2/4 patients) and 10 mg/m 2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and C max from 1–10 mg/m 2 . Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. EU-CTR2006-001345-33

  10. Hot-working behavior of an advanced intermetallic multi-phase γ-TiAl based alloy

    Energy Technology Data Exchange (ETDEWEB)

    Schwaighofer, Emanuel, E-mail: emanuel.schwaighofer@unileoben.ac.at [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria); Clemens, Helmut [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria); Lindemann, Janny [Chair of Physical Metallurgy and Materials Technology, Brandenburg University of Technology, Konrad-Wachsmann-Allee 17, D-03046 Cottbus (Germany); GfE Fremat GmbH, Lessingstr. 41, D-09599 Freiberg (Germany); Stark, Andreas [Institute of Materials Research, Helmholtz-Zentrum Geesthacht, Max-Planck-Str. 1, D-21502 Geesthacht (Germany); Mayer, Svea [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria)

    2014-09-22

    New high-performance engine concepts for aerospace and automotive application enforce the development of lightweight intermetallic γ-TiAl based alloys with increased high-temperature capability above 750 °C. Besides an increased creep resistance, the alloy system must exhibit sufficient hot-workability. However, the majority of current high-creep resistant γ-TiAl based alloys suffer from poor workability, whereby grain refinement and microstructure control during hot-working are key factors to ensure a final microstructure with sufficient ductility and tolerance against brittle failure below the brittle-to-ductile transition temperature. Therefore, a new and advanced β-solidifying γ-TiAl based alloy, a so-called TNM alloy with a composition of Ti–43Al–4Nb–1Mo–0.1B (at%) and minor additions of C and Si, is investigated by means of uniaxial compressive hot-deformation tests performed with a Gleeble 3500 simulator within a temperature range of 1150–1300 °C and a strain rate regime of 0.005–0.5 s{sup −1} up to a true deformation of 0.9. The occurring mechanisms during hot-working were decoded by ensuing constitutive modeling of the flow curves by a novel phase field region-specific surface fitting approach via a hyperbolic-sine law as well as by evaluation through processing maps combined with microstructural post-analysis to determine a safe hot-working window of the refined TNM alloy. Complementary, in situ high energy X-ray diffraction experiments in combination with an adapted quenching and deformation dilatometer were conducted for a deeper insight about the deformation behavior of the alloy, i.e. phase fractions and texture evolution as well as temperature uncertainties arising during isothermal and non-isothermal compression. It was found that the presence of β-phase and the contribution of particle stimulated nucleation of ζ-Ti{sub 5}Si{sub 3} silicides and h-type carbides Ti{sub 2}AlC enhance the dynamic recrystallization behavior during

  11. Hot-working behavior of an advanced intermetallic multi-phase γ-TiAl based alloy

    International Nuclear Information System (INIS)

    Schwaighofer, Emanuel; Clemens, Helmut; Lindemann, Janny; Stark, Andreas; Mayer, Svea

    2014-01-01

    New high-performance engine concepts for aerospace and automotive application enforce the development of lightweight intermetallic γ-TiAl based alloys with increased high-temperature capability above 750 °C. Besides an increased creep resistance, the alloy system must exhibit sufficient hot-workability. However, the majority of current high-creep resistant γ-TiAl based alloys suffer from poor workability, whereby grain refinement and microstructure control during hot-working are key factors to ensure a final microstructure with sufficient ductility and tolerance against brittle failure below the brittle-to-ductile transition temperature. Therefore, a new and advanced β-solidifying γ-TiAl based alloy, a so-called TNM alloy with a composition of Ti–43Al–4Nb–1Mo–0.1B (at%) and minor additions of C and Si, is investigated by means of uniaxial compressive hot-deformation tests performed with a Gleeble 3500 simulator within a temperature range of 1150–1300 °C and a strain rate regime of 0.005–0.5 s −1 up to a true deformation of 0.9. The occurring mechanisms during hot-working were decoded by ensuing constitutive modeling of the flow curves by a novel phase field region-specific surface fitting approach via a hyperbolic-sine law as well as by evaluation through processing maps combined with microstructural post-analysis to determine a safe hot-working window of the refined TNM alloy. Complementary, in situ high energy X-ray diffraction experiments in combination with an adapted quenching and deformation dilatometer were conducted for a deeper insight about the deformation behavior of the alloy, i.e. phase fractions and texture evolution as well as temperature uncertainties arising during isothermal and non-isothermal compression. It was found that the presence of β-phase and the contribution of particle stimulated nucleation of ζ-Ti 5 Si 3 silicides and h-type carbides Ti 2 AlC enhance the dynamic recrystallization behavior during deformation within

  12. A review of modern advances in analyses and applications of single-phase natural circulation loop in nuclear thermal hydraulics

    International Nuclear Information System (INIS)

    Basu, Dipankar N.; Bhattacharyya, Souvik; Das, P.K.

    2014-01-01

    Highlights: • Comprehensive review of state-of-the-art on single-phase natural circulation loops. • Detailed discussion on growth in solar thermal system and nuclear thermal hydraulics. • Systematic development in scaling methodologies for fabrication of test facilities. • Importance of numerical modeling schemes for stability assessment using 1-D codes. • Appraisal of current trend of research and possible future directions. - Abstract: A comprehensive review of single-phase natural circulation loop (NCL) is presented here. Relevant literature reported since the later part of 1980s has been meticulously surveyed, with occasional obligatory reference to a few pioneering studies originating prior to that period, summarizing the key observations and the present trend of research. Development in the concept of buoyancy-induced flow is discussed, with introduction to flow initiation in an NCL due to instability. Detailed discussion on modern advancement in important application areas like solar thermal systems and nuclear thermal hydraulics are presented, with separate analysis for various reactor designs working on natural circulation. Identification of scaling criteria for designing lab-scale experimental facilities has gone through a series of modification. A systematic analysis of the same is presented, considering the state-of-the-art knowledge base. Different approaches have been followed for modeling single-phase NCLs, including simplified Lorenz system mostly for toroidal loops, 1-D computational modeling for both steady-state and stability characterization and 3-D commercial system codes to have a better flow visualization. Methodical review of the relevant studies is presented following a systematic approach, to assess the gradual progression in understanding of the practical system. Brief appraisal of current research interest is reported, including the use of nanofluids for fluid property augmentation, marine reactors subjected to rolling waves

  13. A review of modern advances in analyses and applications of single-phase natural circulation loop in nuclear thermal hydraulics

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Dipankar N., E-mail: dipankar.n.basu@gmail.com [Department of Mechanical Engineering, Indian Institute of Technology Guwahati, Guwahati 781039 (India); Bhattacharyya, Souvik; Das, P.K. [Department of Mechanical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302 (India)

    2014-12-15

    Highlights: • Comprehensive review of state-of-the-art on single-phase natural circulation loops. • Detailed discussion on growth in solar thermal system and nuclear thermal hydraulics. • Systematic development in scaling methodologies for fabrication of test facilities. • Importance of numerical modeling schemes for stability assessment using 1-D codes. • Appraisal of current trend of research and possible future directions. - Abstract: A comprehensive review of single-phase natural circulation loop (NCL) is presented here. Relevant literature reported since the later part of 1980s has been meticulously surveyed, with occasional obligatory reference to a few pioneering studies originating prior to that period, summarizing the key observations and the present trend of research. Development in the concept of buoyancy-induced flow is discussed, with introduction to flow initiation in an NCL due to instability. Detailed discussion on modern advancement in important application areas like solar thermal systems and nuclear thermal hydraulics are presented, with separate analysis for various reactor designs working on natural circulation. Identification of scaling criteria for designing lab-scale experimental facilities has gone through a series of modification. A systematic analysis of the same is presented, considering the state-of-the-art knowledge base. Different approaches have been followed for modeling single-phase NCLs, including simplified Lorenz system mostly for toroidal loops, 1-D computational modeling for both steady-state and stability characterization and 3-D commercial system codes to have a better flow visualization. Methodical review of the relevant studies is presented following a systematic approach, to assess the gradual progression in understanding of the practical system. Brief appraisal of current research interest is reported, including the use of nanofluids for fluid property augmentation, marine reactors subjected to rolling waves

  14. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

    Science.gov (United States)

    Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

    2017-08-01

    Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

  15. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.

    Science.gov (United States)

    Cheng, Ann-Lii; Kang, Yoon-Koo; Lin, Deng-Yn; Park, Joong-Won; Kudo, Masatoshi; Qin, Shukui; Chung, Hyun-Cheol; Song, Xiangqun; Xu, Jianming; Poggi, Guido; Omata, Masao; Pitman Lowenthal, Susan; Lanzalone, Silvana; Yang, Liqiang; Lechuga, Maria Jose; Raymond, Eric

    2013-11-10

    Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS). Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%). OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.

  16. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    Directory of Open Access Journals (Sweden)

    Guetz S

    2017-02-01

    Full Text Available Sylvia Guetz,1,* Amanda Tufman,2,* Joachim von Pawel,3 Achim Rittmeyer,4 Astrid Borgmeier,2 Pierre Ferré,5 Birgit Edlich,6 Rudolf Maria Huber2 1Ev. Diakonissenkrankenhaus Leipzig, Leipzig, 2University Hospital Munich and Thoracic Oncology Centre Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (DZL CPC-M, Munich, 3Asklepios Fachkliniken Muenchen-Gauting, Gauting, 4Lungenfachklinik Immenhausen, Immenhausen, Germany; 5Pierre Fabre Pharmaceuticals, Oncology Research and Development Center, Toulouse, France; 6Pierre Fabre Pharma GmbH, Freiburg, Germany *These authors contributed equally to this work Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo in advanced non-small-cell lung cancer (NSCLC. Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP, overall survival (OS and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs. Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21

  17. The facilitating role of chemotherapy in the palliative phase of cancer: qualitative interviews with advanced cancer patients.

    Directory of Open Access Journals (Sweden)

    Hilde M Buiting

    Full Text Available OBJECTIVE: To explore the extent to which patients have a directing role in decisions about chemotherapy in the palliative phase of cancer and (want to anticipate on the last stage of life. DESIGN: Qualitative interview study. METHODS: In depth-interviews with 15 patients with advanced colorectal or breast cancer at the medical oncology department in a Dutch teaching hospital; interviews were analysed following the principles of thematic content-analysis. RESULTS: All patients reported to know that the chemotherapy they received was with palliative intent. Most of them did not express the wish for information about (other treatment options and put great trust in their physicians' treatment advice. The more patients were aware of the severity of their disease, the more they seemed to 'live their life' in the present and enjoy things besides having cancer. Such living in the present seemed to be facilitated by the use of chemotherapy. Patients often considered the 'chemotherapy-free period' more stressful than periods when receiving chemotherapy despite their generally improved physical condition. Chemotherapy (regardless of side-effects seemed to shift patients' attention away from the approaching last stage of life. Interestingly, although patients often discussed advance care planning, they were reluctant to bring on end-of-life issues that bothered them at that specific moment. Expressing real interest in people 'as a person' was considered an important element of appropriate care. CONCLUSIONS: Fearing their approaching death, patients deliberately focus on living in the present. Active (chemotherapy treatment facilitates this focus, regardless of the perceived side-effects. However, if anxiety for what lies ahead is the underlying reason for treatment, efforts should be made in assisting patients to find other ways to cope with this fear. Simultaneously, such an approach may reduce the use of burdensome and sometimes costly treatment in the

  18. Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

    Science.gov (United States)

    Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

    2011-06-15

    Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

  19. Chemo-radiotherapy plus hyperthermia in locally advanced cervical cancer: preliminary results of an institutional phase II study

    International Nuclear Information System (INIS)

    Gabbani, M.; Marciai, N.; Maluta, S.; Griso, C.; Merlin, F.; Cassandrini, P.; Giudici, S.; Franchi, M.; Zanini, L.

    2005-01-01

    Full text: Radiotherapy given concurrently with a cisplatin-based regimen has shown a benefit in patients with locally advanced cervical cancer so becoming the new standard treatment according to EBM criteria. Addition of hyperthermia to radiotherapy has also been proved to yield an advantage in survival and local control in pts affected by recurrent and local advanced cervical cancer in the Dutch Phase III trial so that the Consensus Forum of Kadota (Osaha June 2004) included cervical cancer among tumors treatable with hyperthermia. In our institutional multidisciplinary team a pilot study has been designed in order to evaluate feasibility, outcome and toxicity of tri-modality treatment in pts with locally advanced cervical cancer in our daily practice. Since January 2003 to now eight patients affected by cervical cancer with stage IB2 through IVA N0-N+ pelvic or paraaortic were entered the study. Six patients were treated at initial diagnosis and two patients after chemotherapy which had achieved stable disease. Treatment regimen consisted in 5 courses of weekly chemotherapy (cisplatin 40 mg/mq) with concurrent external radiotherapy to a total dose of 64-66 Gy on CTV1 and 45 Gy on para-aortic nodes plus boost in pts with enlarged nodes identified by imaging. Five weekly sessions of hyperthermia were performed by using BSD 2000 system and sigma 60 applicator. No significant toxicity occurred and all of the patients completed tri-modality treatment in accordance with the study protocol. Seven pts experienced a complete clinical remission and one patient a partial remission as defined by clinical and imaging examinations. After four months from the end of the treatment a patient with Stage IIB bulky tumor plus one pelvic positive node who was in complete remission (Clinical examination, MRI and TAC-PET three months from the end of the treatment were negative for evidence of disease) developed a bleeding recto-vaginal fistula plus central pelvic necrosis for which an

  20. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

  1. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

  2. Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumours

    International Nuclear Information System (INIS)

    Vink, Stefan R.; Schellens, Jan H.M.; Beijnen, Jos H.; Sindermann, Herbert; Engel, Juergen; Dubbelman, Ria; Moppi, Gemi; Hillebrand, Michel J.X.; Bartelink, Harry; Verheij, Marcel

    2006-01-01

    Purpose: Perifosine is an orally applicable, membrane-targeted alkylphosphocholine analogue with antitumour activity and radiosensitising properties in preclinical models. The purpose of this phase I study was to determine the feasibility and tolerability of concurrent daily perifosine and radiation in patients with advanced cancer. Patients and methods: Starting dose of perifosine was 50 mg/day; dose escalation was in steps of 50 mg. Daily administration commenced 2 days before radiotherapy and was continued throughout the radiation treatment. At least three patients were entered at each dose level; at the 150 mg/day level 10 patients were included. Pharmacokinetic sampling was performed weekly pre-dosing. Twenty-one patients were entered. Tumour types included NSCLC (n = 17), prostate, oesophageal, colon and bladder cancer. Most patients (16/21) had received prior chemotherapy; none radiotherapy. Median number of daily perifosine administrations was 31 (range 24-53). Mean radiation dose (BED 1 ) was 59.8 Gy (range 50.7-87.5 Gy in 13-28 fractions). Results: Major drug-related toxicities according to CTC criteria were nausea in 57%, fatigue in 48%, vomiting in 38%, diarrhoea in 38% and anorexia in 19%. No bone marrow toxicity was observed. DLT (nausea/vomiting) was encountered in two of five patients at the 200 mg/day dose level. Dose-dependent steady-state plasma levels were reached after 1 week. Major radiotherapy-related acute toxicity consisted of dysphagia in 38% and pneumonitis in 29%. Conclusion: Perifosine can be safely combined with fractionated radiotherapy. A dosage of 150 mg/day, to be started at least 1 week prior to radiotherapy, is recommended for phase II evaluation

  3. Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

    Directory of Open Access Journals (Sweden)

    Takeshi Ishikawa

    Full Text Available BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT and that fibronectin CH296 (FN-CH296 together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835.

  4. Advanced functional materials in solid phase extraction for ICP-MS determination of trace elements and their species - A review.

    Science.gov (United States)

    He, Man; Huang, Lijin; Zhao, Bingshan; Chen, Beibei; Hu, Bin

    2017-06-22

    For the determination of trace elements and their species in various real samples by inductively coupled plasma mass spectrometry (ICP-MS), solid phase extraction (SPE) is a commonly used sample pretreatment technique to remove complex matrix, pre-concentrate target analytes and make the samples suitable for subsequent sample introduction and measurements. The sensitivity, selectivity/anti-interference ability, sample throughput and application potential of the methodology of SPE-ICP-MS are greatly dependent on SPE adsorbents. This article presents a general overview of the use of advanced functional materials (AFMs) in SPE for ICP-MS determination of trace elements and their species in the past decade. Herein the AFMs refer to the materials featuring with high adsorption capacity, good selectivity, fast adsorption/desorption dynamics and satisfying special requirements in real sample analysis, including nanometer-sized materials, porous materials, ion imprinting polymers, restricted access materials and magnetic materials. Carbon/silica/metal/metal oxide nanometer-sized adsorbents with high surface area and plenty of adsorption sites exhibit high adsorption capacity, and porous adsorbents would provide more adsorption sites and faster adsorption dynamics. The selectivity of the materials for target elements/species can be improved by using physical/chemical modification, ion imprinting and restricted accessed technique. Magnetic adsorbents in conventional batch operation offer unique magnetic response and high surface area-volume ratio which provide a very easy phase separation, greater extraction capacity and efficiency over conventional adsorbents, and chip-based magnetic SPE provides a versatile platform for special requirement (e.g. cell analysis). The performance of these adsorbents for the determination of trace elements and their species in different matrices by ICP-MS is discussed in detail, along with perspectives and possible challenges in the future

  5. Needs of people with advanced dementia in their final phase of life: A multi-perspective qualitative study in nursing homes.

    Science.gov (United States)

    Schmidt, Holger; Eisenmann, Yvonne; Golla, Heidrun; Voltz, Raymond; Perrar, Klaus Maria

    2018-03-01

    People with advanced dementia present an important target group for palliative care. They suffer a range of symptoms, and their verbal communication abilities are highly restricted. At present, little is known about their needs in the final phase of life. To identify the needs of people with advanced dementia in their final phase of life and to explore the aspects relevant to first recognize and then meet these needs. Multi-perspective qualitative study using grounded theory methodology conducting group discussions, individual interviews, and participant observation. The study encompassed nursing homes and involved health professionals, relatives, and residents with advanced dementia. Data were collected in six nursing homes. Nine group discussions and three individual interviews were conducted comprising 42 health professionals and 14 relatives. Participant observations aided in giving the perspective of 30 residents with advanced dementia. Data analysis generated a total of 25 physical, psychosocial, and spiritual needs divided into 10 categories. Physical needs were classified as follows: "food intake," "physical well-being," and "physical activity and recovery." Categories of psychosocial needs were classified as follows: "adaptation of stimuli," "communication," "personal attention," "participation," "familiarity and safety," as well as "self-determination." Spiritual needs addressed "religion." The results revealed a multitude of key aspects for recognizing and meeting these needs, stressing the importance of personhood. People with advanced dementia in their final phase of life have a multitude of individual and complex needs. This evidence contributes to narrowing the current research gap, offering an orientation framework for research and practice.

  6. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; von der Maase, Hans; Mead, Graham M

    2012-01-01

    The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival....

  7. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik V; Jensen, Lars Henrik; Sorensen, Morten

    2011-01-01

    (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). Methods. In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours...... and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC. Results. Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1...... and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median...

  8. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  9. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

    NARCIS (Netherlands)

    Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

    2015-01-01

    PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour

  10. A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Nielsen, D L; Sørensen, M

    2012-01-01

    BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid...

  11. A phase I monotherapy study of RG7212, a first-in-class monoclonal antibody targeting TWEAK signaling in patients with advanced cancers

    DEFF Research Database (Denmark)

    Lassen, Ulrik N; Meulendijks, Didier; Siu, Lilian L

    2015-01-01

    activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was conducted in patients with advanced solid tumors expressing Fn14. EXPERIMENTAL DESIGN: Dose escalations, over a 200- to 7,200-mg range, were performed with patients enrolled in weekly (QW), bi-weekly (Q2W), or every...

  12. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer

    DEFF Research Database (Denmark)

    Schlumberger, Martin J; Elisei, Rossella; Bastholt, Lars

    2009-01-01

    PURPOSE: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). PATIENTS A...

  13. Performance evaluation of a full-scale advanced phase isolation ditch process by using real-time control strategies

    International Nuclear Information System (INIS)

    Kim, Hyosoo; Kim, Yejin; Kim, Minsoo; Piao, Wenhua; Kim, Changwon; Gee, Jeasung

    2014-01-01

    This paper proposes real-time control strategies that can be applied in a full-scale advanced phase isolation ditch (APID) process. Real-time operation mode control (OMC) and aeration section control (ASC) strategies were developed to cope more stably with fluctuations in the influent loading and to increase the nitrification and denitrification reactions within the entire volume. The real-time OMC and ASC strategies were evaluated using mathematical models. When the NH 4 -N in the reactor was maintained at a high level, appropriate control actions, such as continuing the aeration state, stopping the influent inflow and increasing the aeration section, were applied in the APID process. In contrast, when the NO X -N in the reactor was maintained at a high level, the non-aeration state, influent inflow, and decreased aeration section were continued. It was concluded that stable operation in the APID process could be achieved by applying real-time OMC and ASC strategies developed in this study

  14. Performance evaluation of a full-scale advanced phase isolation ditch process by using real-time control strategies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyosoo; Kim, Yejin; Kim, Minsoo; Piao, Wenhua; Kim, Changwon [Pusan National University, Busan (Korea, Republic of); Gee, Jeasung [Taiwha Industrial Co. Ltd., Seoul (Korea, Republic of)

    2014-04-15

    This paper proposes real-time control strategies that can be applied in a full-scale advanced phase isolation ditch (APID) process. Real-time operation mode control (OMC) and aeration section control (ASC) strategies were developed to cope more stably with fluctuations in the influent loading and to increase the nitrification and denitrification reactions within the entire volume. The real-time OMC and ASC strategies were evaluated using mathematical models. When the NH{sub 4}-N in the reactor was maintained at a high level, appropriate control actions, such as continuing the aeration state, stopping the influent inflow and increasing the aeration section, were applied in the APID process. In contrast, when the NO{sub X}-N in the reactor was maintained at a high level, the non-aeration state, influent inflow, and decreased aeration section were continued. It was concluded that stable operation in the APID process could be achieved by applying real-time OMC and ASC strategies developed in this study.

  15. Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Morak, Marjolein J.M.; Richel, Dick J.; Eijck, Casper H.J. van; Nuyttens, Joost J.M.E.; Gaast, Ate van der; Vervenne, Walter L.; Padmos, Esther E.; Schaake, Eva E.; Busch, Olivier R.C.; Tienhoven, Geertjan van

    2011-01-01

    Background and purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. Material and methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 x 2.5 Gy radiotherapy combined with UFT 300 mg/m 2 per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

  16. Advanced fabrication method for the preparation of MOF thin films: Liquid-phase epitaxy approach meets spin coating method.

    KAUST Repository

    Chernikova, Valeriya

    2016-07-14

    Here we report a new and advanced method for the fabrication of highly oriented/polycrystalline metal-organic framework (MOF) thin films. Building on the attractive features of the liquid-phase epitaxy (LPE) approach, a facile spin coating method was implemented to generate MOF thin films in a high-throughput fashion. Advantageously, this approach offers a great prospective to cost-effectively construct thin-films with a significantly shortened preparation time and a lessened chemicals and solvents consumption, as compared to the conventional LPE-process. Certainly, this new spin-coating approach has been implemented successfully to construct various MOF thin films, ranging in thickness from a few micrometers down to the nanometer scale, spanning 2-D and 3-D benchmark MOF materials including Cu2(bdc)2•xH2O, Zn2(bdc)2•xH2O, HKUST-1 and ZIF-8. This method was appraised and proved effective on a variety of substrates comprising functionalized gold, silicon, glass, porous stainless steel and aluminum oxide. The facile, high-throughput and cost-effective nature of this approach, coupled with the successful thin film growth and substrate versatility, represents the next generation of methods for MOF thin film fabrication. Thereby paving the way for these unique MOF materials to address a wide range of challenges in the areas of sensing devices and membrane technology.

  17. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Christensen, M G; Friis, E

    1990-01-01

    In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the co......In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor...... of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide...... is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate....

  18. Concurrent chemoradiotherapy in locally advanced carcinoma of the uterine cervix: a phase I/II prospective study

    International Nuclear Information System (INIS)

    Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hye Sook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

    1998-01-01

    Prospective, single arm. Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The international Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4, 140-5, 040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m 2 /day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m 2 /dy intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of 1 of RT. The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and II+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a

  19. Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Cellier, Patrice; Burtin, Pascal; Campion, Loïc; Boisdron-Celle, Michèle; Morel, Alain; Berger, Virginie; Gamelin, Erick; Leduc, Bernard; Martin, Laurent; Vié, Brigitte; Chevelle, Christian; Vendrely, Véronique; Salemkour, Augustin; Carrie, Christian; Calais, Gilles

    2011-01-01

    Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment. This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/ 2 /day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate. Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66

  20. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  1. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.

    Science.gov (United States)

    Borad, Mitesh J; Reddy, Shantan G; Bahary, Nathan; Uronis, Hope E; Sigal, Darren; Cohn, Allen L; Schelman, William R; Stephenson, Joe; Chiorean, E Gabriela; Rosen, Peter J; Ulrich, Brian; Dragovich, Tomislav; Del Prete, Salvatore A; Rarick, Mark; Eng, Clarence; Kroll, Stew; Ryan, David P

    2015-05-01

    TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation. PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979). © 2014 by American Society of

  2. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Valente Nancy

    2005-02-01

    Full Text Available Abstract Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC-derived exosomes (DEX loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC. Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4 and IV (N = 9 NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8, flu like illness (N = 1, and peripheral arm pain (N = 1. The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors

  3. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Patrick J. Mansky

    2013-01-01

    Full Text Available Purpose. European Mistletoe (Viscum album L. extracts (mistletoe are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM and mistletoe in advanced solid cancers (ASC evaluated: (1 safety, toxicity, and maximum tolerated dose (MTD, (2 absolute neutrophil count (ANC recovery, (3 formation of mistletoe lectin antibodies (ML ab, (4 cytokine plasma concentrations, (5 clinical response, and (6 pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT were grade (G 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

  4. SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma.

    Science.gov (United States)

    Schuetze, Scott M; Wathen, J Kyle; Lucas, David R; Choy, Edwin; Samuels, Brian L; Staddon, Arthur P; Ganjoo, Kristen N; von Mehren, Margaret; Chow, Warren A; Loeb, David M; Tawbi, Hussein A; Rushing, Daniel A; Patel, Shreyaskumar R; Thomas, Dafydd G; Chugh, Rashmi; Reinke, Denise K; Baker, Laurence H

    2016-03-15

    Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity. © 2015 American Cancer Society.

  5. Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

    Science.gov (United States)

    Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

    1993-03-15

    To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

  6. Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Wolff, Robert A.; Das, Prajnan; Delclos, Marc E.; Chang, George J.; Hoff, Paulo M.; Eng, Cathy; Brown, Thomas D.; Crane, Christopher H.; Feig, Barry W.; Morris, Jeffrey; Vadhan-Raj, Saroj; Hamilton, Stanley R.; Lin, Edward H.

    2006-01-01

    Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m 2 orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative ≥T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age, 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor ≤5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC

  7. Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with advanced solid tumors.

    Science.gov (United States)

    Lam, Elaine T; Goel, Sanjay; Schaaf, Larry J; Cropp, Gillian F; Hannah, Alison L; Zhou, Yiqing; McCracken, Barbara; Haley, Brandi I; Johnson, Robert G; Mani, Sridhar; Villalona-Calero, Miguel A

    2012-02-01

    First-in-man study of KOS-1584, a second generation epothilone. Patients with advanced solid malignancies received KOS-1584 every 3 weeks until disease progression. Using a modified Fibonacci dose escalation scheme, one patient was enrolled at each dose level until the first instance of grade 2 toxicity. Thereafter, a standard 3 + 3 design was utilized. Sixty-six patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias, and encephalopathy were dose-limiting toxicities (DLTs) at doses ≥36 mg/m(2). At the recommended phase II dose (RP2D), the most common adverse effects were peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of distribution, and half-life of KOS-1584 were 11 ± 6.17 L/h/m(2), 327 ± 161 L/m(2), and 21.9 ± 8.75 h, respectively. The half-life for the seco-metabolite (KOS-1891) was 29.6 ± 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A dose-dependent increase in microtubulin bundle formation was observed at doses ≥27 mg/m(2). Two patients achieved partial responses and 24 patients had stable disease (SD). The RP2D of KOS-1584 is 36 mg/m(2). The lack of severe neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions; favorable pharmacokinetic profile; and early evidence of activity support further evaluation.

  8. Phase I biodistribution and pharmacokinetic study of Lewis Y targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers

    International Nuclear Information System (INIS)

    Herbertson, R. A.; Lee, F. T.; Hopkins, W.; Smyth, F. E.; Murone, C.; Tebbutt, N. C.; Micallef, N.; MacFarlane, D. J.; Bellen, J.; Sonnichsen, D. S.; Brechbiel, M. W.; Scott, A. M.; Lee, T. L.

    2009-01-01

    Full text:Background: The Lewis Y (Ley) antigen is a blood-group related antigen expressed in >70% of solid tumours. This study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 (humanized anti-Ley antibody conjugated with calichaemicin) in patients with advanced Ley expressing epithelial cancers. Methods: There were 2 dose cohorts, (1.0mg/m2 and 2.6mg/m2). Primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. The first cycle was labelled with 111In for biodistribution assessment, and subsequent cycles were administered 3 weekly to a maximum of 6 cycles. Tumour targeting was assessed using SPECT imaging, and pharmacokinetic analysis was based on gamma counting (111In-CMD-193) and ELISA (CMD-193 protein). Results: Nine patients were enrolled, and received 1-6 treatment cycles. Biodistribution imaging demonstrated initial blood pooling, followed by markedly increased hepatic uptake by day 2 (which persisted to day 8), and fast blood clearance. This pattern was seen for all patients, with no significant tumour uptake visualised in any patient. The overall T 1 /2 of 111In-CMD-193 complex formation in blood. One patient had partial metabolic response on 18F-FDG-PET. No radiologic responses were observed. Conclusions: CMD-193 demonstrates rapid blood clearance and increased hepatic uptake compared to prior studies of the original non-conjugated antibody. This trial highlights the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics in clinical development.

  9. Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.

    Science.gov (United States)

    Bines, J; Dienstmann, R; Obadia, R M; Branco, L G P; Quintella, D C; Castro, T M; Camacho, P G; Soares, F A; Costa, M E F

    2014-04-01

    As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR). Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. local trial number, related to the approval by the IRB: CEP 108/06.

  10. Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018-2020 Period Phase 2

    Science.gov (United States)

    Morgenstern, John; Buonanno, Michael; Yao, Jixian; Murugappan, Mugam; Paliath, Umesh; Cheung, Lawrence; Malcevic, Ivan; Ramakrishnan, Kishore; Pastouchenko, Nikolai; Wood, Trevor; hide

    2015-01-01

    Lockheed Martin Aeronautics Company (LM), working in conjunction with General Electric Global Research (GE GR) and Stanford University, executed a 19 month program responsive to the NASA sponsored "N+2 Supersonic Validation: Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018-2020 Period" contract. The key technical objective of this effort was to validate integrated airframe and propulsion technologies and design methodologies necessary to realize a supersonic vehicle capable of meeting the N+2 environmental and performance goals. The N+2 program is aligned with NASA's Supersonic Project and is focused on providing system level solutions capable of overcoming the efficiency, environmental, and performance barriers to practical supersonic flight. The N+2 environmental and performance goals are outlined in the technical paper, AIAA-2014-2138 (Ref. 1) along with the validated N+2 Phase 2 results. Our Phase 2 efforts built upon our Phase 1 studies (Ref. 2) and successfully demonstrated the ability to design and test realistic configurations capable of shaped sonic booms over the width of the sonic boom carpet. Developing a shaped boom configuration capable of meeting the N+2 shaped boom targets is a key goal for the N+2 program. During the LM Phase 1 effort, LM successfully designed and tested a shaped boom trijet configuration (1021) capable of achieving 85 PLdB under track (forward and aft shock) and up to 28 deg off-track at Mach 1.6. In Phase 2 we developed a refined configuration (1044-2) that extended the under 85 PLdB sonic boom level over the entire carpet of 52 deg off-track at a cruise Mach number of 1.7. Further, the loudness level of the configuration throughout operational conditions calculates to an average of 79 PLdB. These calculations rely on propagation employing Burger's (sBOOM) rounding methodology, and there are indications that the configuration average loudness would actually be 75 PLdB. We also added

  11. Study of Pu consumption in advanced light water reactors: Evaluation of GE advanced boiling water reactor plants - compilation of Phase 1B task reports

    International Nuclear Information System (INIS)

    1993-01-01

    This report contains an extensive evaluation of GE advanced boiling water reactor plants prepared for United State Department of Energy. The general areas covered in this report are: core and system performance; fuel cycle; infrastructure and deployment; and safety and environmental approval

  12. Study of Pu consumption in advanced light water reactors: Evaluation of GE advanced boiling water reactor plants - compilation of Phase 1B task reports

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-09-15

    This report contains an extensive evaluation of GE advanced boiling water reactor plants prepared for United State Department of Energy. The general areas covered in this report are: core and system performance; fuel cycle; infrastructure and deployment; and safety and environmental approval.

  13. High Watts per Kilogram - Advanced Integration and Heat Management solar array technology (HaWK-AIHM ), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Small satellite architectures have become a desirable low cost alternative to larger heritage spacecraft for advanced scientific missions. Unfortunately, the...

  14. Alternative Green Technology for Power Generation Using Waste-Heat Energy And Advanced Thermoelectric Materials, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is interested in advancing green technology research for achieving sustainable and environmentally friendly energy sources for both terrestrial and space...

  15. Alternative Green Technology for Power Generation Using Waste-Heat Energy And Advanced Thermoelectric Materials, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is interested in advancing green technology research for achieving sustainable and environmentally friendly energy sources. Thermo-electric power generation...

  16. Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

    International Nuclear Information System (INIS)

    Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A.; Gauler, T.; Bauer, S.; Antoch, G.; Schuette, J.

    2008-01-01

    Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq 111 In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR registered -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

  17. Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group

    DEFF Research Database (Denmark)

    Reichardt, P; Nielsen, Ole Steen; Bauer, S

    2007-01-01

    No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which...... was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent...... agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two...

  18. Combining Advanced Turbulent Mixing and Combustion Models with Advanced Multi-Phase CFD Code to Simulate Detonation and Post-Detonation Bio-Agent Mixing and Destruction

    Science.gov (United States)

    2017-10-01

    Prepared by: School of Aerospace Engineering, Georgia Institute of Technology 270 Ferst Dr Atlanta, GA 30332...METHOD- OLOGY 7 4.1 Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.1.1 Eulerian Gas Phase...from [3] and our simu- lation : our work is able to capture a non linear behaviour . . . . . . . . . . 59 5.44 Pressure profile from the blast wave

  19. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Dellas, Kathrin; Dunst, Jürgen; Höhler, Thomas; Reese, Thomas; Würschmidt, Florian; Engel, Erik; Rödel, Claus; Wagner, Wolfgang; Richter, Michael; Arnold, Dirk

    2013-01-01

    Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m 2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m 2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection

  20. Digital Signal Processing Applications and Implementation for Accelerators Digital Notch Filter with Programmable Delay and Betatron Phase Adjustment for the PS, SPS and LHC Transverse Dampers

    CERN Document Server

    Rossi, V

    2002-01-01

    In the framework of the LHC project and the modifications of the SPS as its injector, I present the concept of global digital signal processing applied to a particle accelerator, using Field Programmable Gate Array (FPGA) technology. The approach of global digital synthesis implements in numerical form the architecture of a system, from the start up of a project and the very beginning of the signal flow. It takes into account both the known parameters and the future evolution, whenever possible. Due to the increased performance requirements of today's projects, the CAE design methodology becomes more and more necessary to handle successfully the added complexity and speed of modern electronic circuits. Simulation is performed both for behavioural analysis, to ensure conformity to functional requirements, and for time signal analysis (speed requirements). The digital notch filter with programmable delay for the SPS Transverse Damper is now fully operational with fixed target and LHC-type beams circulating in t...

  1. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

    OpenAIRE

    Kelly, K; Infante, JR; Taylor, MH; Patel, MR; Wong, DJ; Iannotti, N; Mehnert, JM; Loos, AH; Koch, H; Speit, I; Gulley, JL

    2018-01-01

    © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patient...

  2. Next Generation Advanced Binder Chemistries for High Performance, Environmetally DurableThermal Control Material Systems., Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This innovative SBIR Phase I proposal will develop new binder systems through the systematic investigations to tailor required unique performance properties and...

  3. A non-linear canonical formalism for the coupled synchro-betatron motion of protons with arbitrary energy

    International Nuclear Information System (INIS)

    Barber, D.P.; Ripken, G.; Schmidt, F.

    1987-05-01

    We investigate the motion of protons of arbitrary energy (below and above transition energy) in a storage ring. The motion is described both in terms of the fully six-dimensional formalism with the canonical variables x, p x , z, p z , σ = s - v 0 . t, η = ΔE/E 0 = p σ and in terms of a dispersion formalism with new variables x, p x , z, p z , σ, p σ . Since the dispersion function is introduced into the equations of motion via a canonical transformation the symplectic structure of these equations is completely preserved. In this formulation it is then possible to define three uncoupled linear (unperturbed) oscillation modes which are described by phase ellipses. Perturbations manifest themselves as deviations from these ellipses. The equations of motion are solved within the framework of the fully six-dimensional formalism. (orig.)

  4. Grid-Free LES 3D Vortex Method for the Simulation of Tubulent Flows Over Advanced Lifting Surfaces, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Turbulent flows associated with advanced aerodynamic designs represent a considerable challenge for accurate prediction. For example, the flow past low-speed wings...

  5. Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement (ADVANCE) Technology Development for Resilient Flight Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SSCI proposes to develop and test a framework referred to as the ADVANCE (Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement), within which...

  6. Update of progress for Phase II of B&W`s advanced coal-fired low-emission boiler system

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, D.K. [Babcock & Wilcox, Barberton, OH (United States); Madden, D.A.; Rodgers, L.W. [Babcock & Wilcox, Alliance, OH (United States)] [and others

    1995-11-01

    Over the past five years, advances in emission control techniques at reduced costs and auxiliary power requirements coupled with significant improvements in steam turbine and cycle design have significantly altered the governing criteria by which advanced technologies have been compared. With these advances, it is clear that pulverized coal technology will continue to be competitive in both cost and performance with other advanced technologies such as Integrated Gasification Combined Cycle (IGCC) or first generation Pressurized Fluidized Bed Combustion (PFBC) technologies for at least the next decade. In the early 1990`s it appeared that if IGCC and PFBC could achieve costs comparable to conventional pulverized coal plants, their significantly reduced NO{sub x} and SO{sub 2} emissions would make them more attractive. A comparison of current emission control capabilities shows that all three technologies can already achieve similarly low emissions levels.

  7. ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2010-01-01

    Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited.......Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited....

  8. Engineering development of advanced coal-fired low-emissions boiler system. Phase II subsystem test design and plan - an addendum to the Phase II RD & T Plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    Shortly after the year 2000 it is expected that new generating plants will be needed to meet the growing demand for electricity and to replace the aging plants that are nearing the end of their useful service life. The plants of the future will need to be extremely clean, highly efficient and economical. Continuing concerns over acid rain, air toxics, global climate changes, ozone depletion and solid waste disposal are expected to further then regulations. In the late 1980`s it was commonly believed that coal-fired power plants of the future would incorporate either some form of Integrated Gasification Combined Cycle (IGCC) or first generation Pressurized Fluidized Bed Combustion (PFBS) technologies. However, recent advances In emission control techniques at reduced costs and auxiliary power requirements coupled with significant improvements In steam turbine and cycle design have clearly indicated that pulverized coal technology can continue to be competitive In both cost and performance. In recognition of the competitive potential for advanced pulverized coal-fired systems with other emerging advanced coal-fired technologies, DOE`s Pittsburgh Energy Technology Center (PETC) began a research and development initiative In late 1990 named, Combustion 2000, with the intention of preserving and expanding coal as a principal fuel In the Generation of electrical power. The project was designed for two stages of commercialization, the nearer-term Low Emission Boiler System (LEBS) program, and for the future, the High Performance Power System (HIPPS) program. B&W is participating In the LEBS program.

  9. Waste incineration models for operation optimization. Phase 1: Advanced measurement equipment for improved operation of waste fired plants; Affaldsforbraendingsmodeller til driftsoptimering. Fase 1: Avanceret maeleudstyr til forbedret drift af affaldsfyrede anlaeg

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-06-01

    This report describes results from the PSO projects ELTRA-5294 and ELTRA-5348: Waste incineration models for operation optimization. Phase 1, and Advanced measurement equipment for improved operation of waste fired plants. Phase 1. The two projects form the first step in a project course build on a long-term vision of a fully automatic system using a wide range of advanced measurement data, advanced dynamic models for prediction of operation and advanced regulation methods for optimization of the operation of waste incinerator plants. (BA)

  10. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

    Science.gov (United States)

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

    2015-06-01

    To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

  11. ModelLab: A Cloud-Based Platform to Support Advanced Geospatial Modeling of Earth Observation Data, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In order to promote and facilitate broader use of NASA and other Earth observation data sources, the Phase I research focused on development of a cloud-based...

  12. Advanced Data Mining and Deployment for Integrated Vehicle Health Management and the Space Vehicle Lifecycle, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In a successful Phase 1 project for NASA SBIR topic A1.05, "Data Mining for Integrated Vehicle Health Management," Michigan Aerospace Corporation (MAC) demonstrated...

  13. COUPLING STATE-OF-THE-SCIENCE SUBSURFACE SIMULATION WITH ADVANCED USER INTERFACE AND PARALLEL VISUALIZATION: SBIR Phase I Final Report

    International Nuclear Information System (INIS)

    Hardeman, B.; Swenson, D.; Finsterle, S.; Zhou, Q.

    2008-01-01

    This is a Phase I report on a project to significantly enhance existing subsurface simulation software using leadership-class computing resources, allowing researchers to solve problems with greater speed and accuracy. Subsurface computer simulation is used for monitoring the behavior of contaminants around nuclear waste disposal and storage areas, groundwater flow, environmental remediation, carbon sequestration, methane hydrate production, and geothermal energy reservoir analysis. The Phase I project was a collaborative effort between Thunderhead Engineering (project lead and developers of a commercial pre- and post-processor for the TOUGH2 simulator) and Lawrence Berkeley National Laboratory (developers of the TOUGH2 simulator for subsurface flow). The Phase I project successfully identified the technical approaches to be implemented in Phase II.

  14. SiC-SiC and C-SiC Honeycomb for Advanced Flight Structures, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project builds upon the work done in Phase I with the development of a C-SiC CMC honeycomb material that was successfully tested for mechanical...

  15. Advanced Petroleum-Based Fuels -- Diesel Emissions Control Project (APBF-DEC): Lubricants Project, Phase 2 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    2006-06-01

    This report summarizes the results of the second phase of a lubricants project, which investigated the impact of engine oil formulation on diesel vehicle emissions and the performance of a nitrogen oxide adsorber catalyst (NAC).

  16. SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

    Science.gov (United States)

    Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

    2015-01-01

    Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

  17. Korea advanced liquid metal reactor development - Development of measuring techniques of the sodium two-phase flow

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moo Hwan; Cha, Jae Eun [Pohang University of Science and Technology, Pohang (Korea)

    2000-04-01

    The technology which models and measures the behavior of bubble in liquid sodium is very important to insure the safety of the liquid metal reactor. In this research, we designed/ manufactured each part and loop of experimental facility for sodium two phase flow, and applied a few possible methods, measured characteristic of two phase flow such as bubbly flow. A air-water loop similar to sodium loop on each measuring condition was designed/manufactured. This air-water loop was utilized to acquire many informations which were necessary in designing the two phase flow of sodium and manufacturing experimental facility. Before the manufacture of a electromagnetic flow meter for sodium, the experiment using each electromagnetic flow mete was developed and the air-water loop was performed to understand flow characteristics. Experiments for observing the signal characteristics of flow were performed by flowing two phase mixture into the electromagnetic flow mete. From these experiments, the electromagnetic flow meter was designed and constructed by virtual electrode, its signal processing circuit and micro electro magnet. It was developed to be applicable to low conductivity fluid very successfully. By this experiment with the electromagnetic flow meter, we observed that the flow signal was very different according to void fraction in two phase flow and that probability density function which was made by statistical signal treatment is also different according to flow patterns. From this result, we confirmed that the electromagnetic flow meter could be used to understand the parameters of two phase flow of sodium. By this study, the experimental facility for two phase flow of sodium was constricted. Also the new electromagnetic flow meter was designed/manufactured, and experimental apparatus for two phase flow of air-water. Finally, this study will be a basic tool for measurement of two phase flow of sodium. As the fundamental technique for the applications of sodium at

  18. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Okano, Susumu; Yoshino, Takayuki; Fujii, Masato

    2013-01-01

    We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2-7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85-100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60-95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each). Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck. (author)

  19. Advances in phase space analysis of partial differential equations in honor of Ferruccio Colombini's 60th birthday

    CERN Document Server

    Bove, Antonio; Murthy, MK Venkatesha

    2009-01-01

    This collection of original articles and surveys addresses the recent advances in linear and nonlinear aspects of the theory of partial differential equations. The key topics include operators as "sums of squares" of real and complex vector fields, nonlinear evolution equations, local solvability, and hyperbolic questions.

  20. Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer : A phase II clinical trial

    NARCIS (Netherlands)

    Eisterer, Wolfgang; de Vries, Alexander; Öfner, Dietmar; Rabl, Hans; Koplmüller, Renate; Greil, Richard; Tschmelitsch, Jöerg; Schmid, Rainer; Kapp, Karin; Lukas, Peter; Sedlmayer, Felix; Höfler, Gerald; Gnant, Michael; Thaler, Josef; Widder, Joachim

    2014-01-01

    BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45

  1. Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

    Science.gov (United States)

    Legan, Sandra J.; Donoghue, Kathleen M.; Franklin, Kathleen M.; Duncan, Marilyn J.

    2009-01-01

    The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression. PMID:19297538

  2. Comparison of high-accuracy numerical simulations of black-hole binaries with stationary-phase post-Newtonian template waveforms for initial and advanced LIGO

    International Nuclear Information System (INIS)

    Boyle, Michael; Brown, Duncan A; Pekowsky, Larne

    2009-01-01

    We study the effectiveness of stationary-phase approximated post-Newtonian waveforms currently used by ground-based gravitational-wave detectors to search for the coalescence of binary black holes by comparing them to an accurate waveform obtained from numerical simulation of an equal-mass non-spinning binary black hole inspiral, merger and ringdown. We perform this study for the initial- and advanced-LIGO detectors. We find that overlaps between the templates and signal can be improved by integrating the match filter to higher frequencies than used currently. We propose simple analytic frequency cutoffs for both initial and advanced LIGO, which achieve nearly optimal matches, and can easily be extended to unequal-mass, spinning systems. We also find that templates that include terms in the phase evolution up to 3.5 post-Newtonian (pN) order are nearly always better, and rarely significantly worse, than 2.0 pN templates currently in use. For initial LIGO we recommend a strategy using templates that include a recently introduced pseudo-4.0 pN term in the low-mass (M ≤ 35 M o-dot ) region, and 3.5 pN templates allowing unphysical values of the symmetric reduced mass η above this. This strategy always achieves overlaps within 0.3% of the optimum, for the data used here. For advanced LIGO we recommend a strategy using 3.5 pN templates up to M = 12 M o-dot , 2.0 pN templates up to M = 21 M o-dot , pseudo-4.0 pN templates up to 65 M o-dot , and 3.5 pN templates with unphysical η for higher masses. This strategy always achieves overlaps within 0.7% of the optimum for advanced LIGO.

  3. Performance Evaluation of Advanced Retrofit Roof Technologies Using Field-Test Data Phase Three Final Report, Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Kaushik [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Childs, Phillip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Atchley, Jerald Allen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    This article presents some miscellaneous data from two low-slope and two steep-slope experimental roofs. The low-slope roofs were designed to compare the performance of various roof coatings exposed to natural weatherization. The steep-slope roofs contained different combinations of phase change material, rigid insulation, low emittance surface and above-sheathing ventilation, with standing-seam metal panels on top. The steep-slope roofs were constructed on a series of adjacent attics separated at the gables using thick foam insulation. This article describes phase three (3) of a study that began in 2009 to evaluate the energy benefits of a sustainable re-roofing technology utilizing standing-seam metal roofing panels combined with energy efficient features like above-sheathing-ventilation (ASV), phase change material (PCM) and rigid insulation board. The data from phases 1 and 2 have been previously published and reported [Kosny et al., 2011; Biswas et al., 2011; Biswas and Childs, 2012; Kosny et al., 2012]. Based on previous data analyses and discussions within the research group, additional test roofs were installed in May 2012, to test new configurations and further investigate different components of the dynamic insulation systems. Some experimental data from phase 3 testing from May 2012 to December 2013 and some EnergyPlus modeling results have been reported in volumes 1 and 3, respectively, of the final report [Biswas et al., 2014; Biswas and Bhandari, 2014].

  4. Results of the Workshop on Two-Phase Flow, Fluid Stability and Dynamics: Issues in Power, Propulsion, and Advanced Life Support Systems

    Science.gov (United States)

    McQuillen, John; Rame, Enrique; Kassemi, Mohammad; Singh, Bhim; Motil, Brian

    2003-01-01

    The Two-phase Flow, Fluid Stability and Dynamics Workshop was held on May 15, 2003 in Cleveland, Ohio to define a coherent scientific research plan and roadmap that addresses the multiphase fluid problems associated with NASA s technology development program. The workshop participants, from academia, industry and government, prioritized various multiphase issues and generated a research plan and roadmap to resolve them. This report presents a prioritization of the various multiphase flow and fluid stability phenomena related primarily to power, propulsion, fluid and thermal management and advanced life support; and a plan to address these issues in a logical and timely fashion using analysis, ground-based and space-flight experiments.

  5. Advanced heat pump for the recovery of volatile organic compounds. Phase 1, Conceptual design of an advanced Brayton cycle heat pump for the recovery of volatile organic compounds: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    Emissions of Volatile Organic Compounds (VOC) from stationary industrial and commercial sources represent a substantial portion of the total US VOC emissions. The ``Toxic-Release Inventory`` of The US Environmental Protection Agency estimates this to be at about 3 billion pounds per year (1987 estimates). The majority of these VOC emissions are from coating processes, cleaning processes, polymer production, fuel production and distribution, foam blowing,refrigerant production, and wood products production. The US Department of Energy`s (DOE) interest in the recovery of VOC stems from the energy embodied in the recovered solvents and the energy required to dispose of them in an environmentally acceptable manner. This Phase I report documents 3M`s work in close working relationship with its subcontractor Nuclear Consulting Services (Nucon) for the preliminary conceptual design of an advanced Brayton cycle heat pump for the recovery of VOC. Nucon designed Brayton cycle heat pump for the recovery of methyl ethyl ketone and toluene from coating operations at 3M Weatherford, OK, was used as a base line for the work under cooperative agreement between 3M and ODE. See appendix A and reference (4) by Kovach of Nucon. This cooperative agreement report evaluates and compares an advanced Brayton cycle heat pump for solvent recovery with other competing technologies for solvent recovery and reuse. This advanced Brayton cycle heat pump is simple (very few components), highly reliable (off the shelf components), energy efficient and economically priced.

  6. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  7. Flight service evaluation of an advanced composite empennage component on commercial transport aircraft. Phase 1: Engineering development

    Science.gov (United States)

    Ary, A.; Axtell, C.; Fogg, L.; Jackson, A.; James, A. M.; Mosesian, B.; Vanderwier, J.; Vanhamersveld, J.

    1976-01-01

    The empennage component selected for this program is the vertical fin box of the L-1011 aircraft. The box structure extends from the fuselage production joint to the tip rib and includes the front and rear spars. Various design options were evaluated to arrive at a configuration which would offer the highest potential for satisfying program objectives. The preferred configuration selected consists of a hat-stiffened cover with molded integrally stiffened spars, aluminum trussed composite ribs, and composite miniwich web ribs with integrally molded caps. Material screening tests were performed to select an advanced composite material system for the Advanced Composite Vertical Fin (ACFV) that would meet the program requirements from the standpoint of quality, reproducibility, and cost. Preliminary weight and cost analysis were made, targets established, and tracking plans developed. These include FAA certification, ancillary test program, quality control, and structural integrity control plans.

  8. An Advanced Computational Approach to System of Systems Analysis & Architecting Using Agent-Based Behavioral Model: Phase 2

    Science.gov (United States)

    2013-11-18

    for each valid interface between the systems. The factor is proportional to the count of feasible interfaces in the meta-architecture framework... proportional to the square root of the sector area being covered by each type of system, plus some time for transmitting data to, and double checking by, the...22] J.-H. Ahn, "An Archietcture Description method for Acknowledged System of Systems based on Federated Architeture ," in Advanced Science and

  9. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

    2007-01-01

    Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m 2 /day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m 2 /day, 3 at 70 mg/m 2 /day, and 10 at 80 mg/m 2 /day. Though 1 patient at the final dose level (80 mg/m 2 /day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m 2 /day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated

  10. Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma: Results of a Randomised Phase III Trial (METEOR

    Directory of Open Access Journals (Sweden)

    Toni Choueiri

    2015-11-01

    Full Text Available The METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma (RCC was reported by Prof Choueiri at the European Cancer Congress 2015. This presentation follows the publication in the New England Journal of Medicine of the METEOR trial back-to-back with the CheckMate 025 trial of nivolumab versus everolimus in the same patient setting. Excitingly, these trials demonstrated, for the first time, significant benefits over the standard of care for heavily pre-treated patients with advanced RCC. Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI aims to address the challenge of resistance to targeted therapy with TKIs. While the METEOR trial has not yet reached its final analysis of overall survival (OS, the clear progression-free survival (PFS benefit, acceptable safety profile, and similar tolerability to other TKIs shown by cabozantinib indicate that this represents a promising new treatment option for second-line or subsequent therapy for patients with advanced RCC.

  11. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P

    2008-01-01

    PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was comp...

  12. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

    NARCIS (Netherlands)

    E. van den Neste (Eric); J.-L. André (Jean-Luc); Gastinne, T. (Thomas); A. Stamatoullas (Aspasia); C. Haioun (Corinne); Belhabri, A. (Amine); O. Reman (Oumédaly); O. Casasnovas (O.); H. Ghesquieres; G.E.G. Verhoef (Gregor); Claessen, M.-J. (Marie-José); H.A. Poirel (Hélène A); M.-C. Copin; Dubois, R. (Romain); P. Vandenberghe (Peter); Stoian, I.-A. (Ioanna-Andrea); Cottereau, A.S. (Anne S.); Bailly, S. (Sarah); L. Knoops (Laurent); F. Morschhauser (Frank)

    2018-01-01

    textabstractJAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we

  13. Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer--Gynaecological Cancer Group)

    NARCIS (Netherlands)

    Witteveen, P. O.; van der Velden, J.; Vergote, I.; Guerra, C.; Scarabeli, C.; Coens, C.; Demonty, G.; Reed, N.

    2009-01-01

    No standard treatment options are available for patients with advanced, recurrent or metastatic vulvar carcinoma not amenable for locoregional treatment. In this phase II study, patients with advanced vulvar cancer received paclitaxel (Taxol) every 3 weeks for up to 10 cycles. Primary objective was

  14. TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

    Science.gov (United States)

    Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

    2012-09-01

    The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

  15. In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

    Science.gov (United States)

    Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

    2014-08-01

    The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI conditioning regimens for allo-SCT in advanced-phase CML.

  16. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m 2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m 2 /day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  17. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children' s Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  18. A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas.

    Science.gov (United States)

    Ansari, M; Omidvari, S; Mosalaei, A; Ahmadloo, N; Mosleh-Shirazi, M A; Mohammadianpanah, M

    2011-03-01

    The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles of induction chemotherapy with docetaxel (75 mg/m(2)), cisplatin (40 mg/m(2)) (days 1-2), and 5-FU (500 mg/m(2), days 1-3), repeated every 21 days. Following induction chemotherapy, all patients underwent concurrent chemoradiotherapy using weekly cisplatin (30 mg/m(2)) and a median total dose of 70 Gy was delivered. Clinical response rate and toxicity were the primary and secondary end-points of the study. There were 31 men and 15 women. All patients had non-metastatic stage IV (T2-3N2-3 or T4N0-3) of disease. Overall and complete response rates were 74% and 24% respectively. Advanced T4 classification was associated with poorer response rate (p value=0.042). The major (grade 3-4) treatment-related toxicities were myelosuppression (78%), anorexia (13%), diarrhea (7%), emesis (11%) and stomatitis/pharyngitis (24%). In comparison with the data of historical published trials of the PF regimen, the TPF regimen was more effective. However, the TPF regimen appears to be associated with a higher incidence of major toxicities. Therefore, our limited findings support the TPF regimen as an alternative chemotherapeutic regimen for advanced head and neck carcinomas.

  19. Phase II study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ou Dan; He Xiayun; Hu Chaosu; Ying Hongmei; Zhu Guopei

    2012-01-01

    Objective: To evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP) chemotherapy combined with intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: 71 patients (Stage III: 41, Stage IV A : 30) with locoregionally advanced NPC were entered this study. Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m 2 intravenously on d1-3 and gemcitabine 1000 mg/m 2 in 30 minutes intravenous infusion on days 1 and 8, every 3 weeks for 2 cycles. Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy. The prescription doses was 66.0-70.4 Gy to the gross tumor volume, 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume, 54 Gy to the low-risk clinical target volume. Results: The overall response rate to neoadjuvant chemotherapy was 91.2%, acute toxicity was mainly grade 1-2 myleosuppression. All patients completed IMRT. The median follow-up duration was 38 months. The 3-year nasopharyngeal local control, regional control, distant metastasis-free survival rate and overall survival rate were 93%, 99%, 91%, 90%, respectively. Severe late toxicities included grade 3 trismus in 1 patient, grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients, respectively. No grade 4 late toxicities were observed. Conclusions: The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated, convenient, effective, and warrants further studies of more proper cycles of GP regimen. (authors)

  20. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea.

    Science.gov (United States)

    Verstovsek, Srdan; Passamonti, Francesco; Rambaldi, Alessandro; Barosi, Giovanni; Rosen, Peter J; Rumi, Elisa; Gattoni, Elisabetta; Pieri, Lisa; Guglielmelli, Paola; Elena, Chiara; He, Shui; Contel, Nancy; Mookerjee, Bijoyesh; Sandor, Victor; Cazzola, Mario; Kantarjian, Hagop M; Barbui, Tiziano; Vannucchi, Alessandro M

    2014-02-15

    Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial. Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to cell and platelet counts, and reduction in PV-associated symptoms. Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification. Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

  1. PowerGuard{reg_sign} Advanced Manufacturing; PVMaT Phase 1 Final Technical Report: June 1, 1998 to September 30, 1999

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, M. C.; Dinwoodie, T. L.; O' Brian, C.; Botkin, J.; Ansley, J.

    2000-06-14

    During Phase 1 of PowerGuard{reg_sign} Advanced Manufacturing, PowerLight Corporation accomplished the following advancements: (1) Decreased system cost by 15%; (2) Increased PowerGuard tile production capacity from 5 MW/year to 8 MW/yr; (3) Established a manufacturing layout master plan for sequential integration of semi-automated and automated component workstations; (4) Defined semi-automation or automation of selected stages of the existing tile fabrication sequence, including PV module preparation, XPS processing, and coating; (5) Completed the advancement of several design improvements to the grid-tied inverter control board, including controller redesign, integrated data acquisition system (DAS), and communications for audit-worthy verification of PV system performance; (6) Conformed to NEPA, OSHA, and other federal and state regulations applicable to the proposed production process and mitigated potential for waste streams; (7) Initiated Underwriters Laboratories listings and international certifications on PowerGuard improvements; (8) Developed finance packages and integrated warranties; (9) Evaluated commercial demonstrations that incorporated the new design features and manufacturing process.

  2. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    Science.gov (United States)

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  3. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

    DEFF Research Database (Denmark)

    Burgdorf, S K; Fischer, A; Claesson, M H

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.......Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...

  4. Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

    Science.gov (United States)

    Chawla, Sant P; Cranmer, Lee D; Van Tine, Brian A; Reed, Damon R; Okuno, Scott H; Butrynski, James E; Adkins, Douglas R; Hendifar, Andrew E; Kroll, Stew; Ganjoo, Kristen N

    2014-10-10

    TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). © 2014 by American Society of Clinical Oncology.

  5. Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer.

    Science.gov (United States)

    Yoo, Changhoon; Ryu, Min-Hee; Na, Young-Soon; Ryoo, Baek-Yeol; Lee, Chae-Won; Maeng, Jeheon; Kim, Se-Yeon; Koo, Dong Hoe; Park, Inkeun; Kang, Yoon-Koo

    2014-04-01

    A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat was dosed at 300-400 mg once daily on Days 1-14, capecitabine at 800-1,000 mg/m(2) twice daily on Days 1-14, and cisplatin at 60-80 mg/m(2) on Day 1. To assess the pharmacodynamics of vorinostat, histone H3 acetylation was assessed in peripheral blood mononuclear cells before the study treatment and at Day 8 of cycle 1. In total, 30 patients with unresectable or metastatic gastric adenocarcinoma were included. Dose-limiting toxicities were thrombocytopenia, fatigue, stomatitis, and anorexia. The following doses were recommended for phase II trial: 400 mg of vorinostat once daily, 1,000 mg/m(2) of capecitabine twice daily, and 60 mg/m(2) of cisplatin. The most common grade 3-4 toxicities were neutropenia (47 %), anorexia (20 %), thrombocytopenia (17 %), and fatigue (13 %). In overall, response rate was 56 % (95 % confidence interval [CI]: 32-81). With a median follow-up of 14.1 months, the median progression-free survival and overall survival were 7.1 months (95 % CI: 3.8-10.3) and 18.0 months (95 % CI: 4.8-31.1), respectively. The change in H3 acetylation after treatment with vorinostat correlated significantly with the vorinostat dose (300 vs. 400 mg/day) and the baseline level of H3 acetylation before treatment. Three-weekly vorinostat-XP regimen is feasible and recommended for further development in advanced gastric cancer.

  6. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

    Science.gov (United States)

    Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

    2018-04-01

    In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.

    Science.gov (United States)

    Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; van Baren, Nicolas; Lucas, Sophie; Kvistborg, Pia; Thielemans, Kris; Neyns, Bart

    2016-04-20

    Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma. Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point. The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma. © 2016 by American Society of Clinical Oncology.

  8. An hour of bright white light in the early morning improves performance and advances sleep and circadian phase during the Antarctic winter.

    Science.gov (United States)

    Corbett, R W; Middleton, B; Arendt, J

    2012-09-13

    Previous work has demonstrated that exposure to an hour of bright light in the morning and the evening during the Polar winter has beneficial effects on circadian phase. This study investigated the effect of a single hour of bright white morning light on circadian phase, sleep, alertness and cognitive performance. Nine individuals (eight male, one female, median age 30 years), wintering at Halley Research Station (75°S), Antarctica from 7th May until 6th August 2007, were exposed to bright white light for a fortnight from 08:30 to 09:30 h, with two fortnight control periods on either side. This sequence was performed twice, before and following Midwinter. Light exposure, sleep and alertness were assessed daily by actigraphy, sleep diaries and subjective visual analogue scales. Circadian phase (assessed by urinary 6-sulphatoxymelatonin rhythm) and cognitive performance were evaluated at the end of each fortnight. During light exposure circadian phase was advanced from 4.97 ± 0.96 decimal hours (dh) (mean ± SD) to 4.08 ± 0.68 dh (p = 0.003). Wake-up time was shifted by a similar margin from 8.45 ± 1.83 dh to 7.59 ± 0.78 dh (p < 0.001). Sleep start time was also advanced (p = 0.047) but by a lesser amount, consequently, actual sleep time was slightly reduced. There was no change in objective or subjective measures of sleep quality or subjective measures of alertness. An improvement in cognitive performance was found with both the Single Letter Cancellation Test (p < 0.001) and the Digit Symbol Substitution Test (p = 0.026) with preserved circadian variation. These beneficial effects of a single short duration light treatment may have implications not only for the Antarctic but other remote environments where access to natural light and delayed circadian phase, is problematic. These results require validation in larger studies at varying locations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Advanced Control Strategies to Enable a More Wide-Scale Adoption of Single-Phase Photovoltaic Systems

    DEFF Research Database (Denmark)

    Yang, Yongheng

    , a thorough evaluation of those topologies in terms of e.g. efficiency, reliability, leakage current mitigation ability, and reactive power injection capability has been presented in Chapter 3, where a multidisciplinary assessment approach with characterized features of energy production estimation...... and lifetime prediction based on mission profiles (e.g. solar irradiance level and ambient temperature) has been proposed. Grid detection and synchronization techniques have also been discussed in Chapter 2, since they are of importance in the control of single-phase systems both in normal operation mode...

  10. A multicenter phase II trial of carboplatin and cetuximab for treatment of advanced nonsmall cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Bradford, Daniel S; Hensing, Thomas A; LaRocca, Renato V; Saleh, Mansoor; Evans, Tracey; Bakri, Kamal; Socinski, Mark A

    2010-02-01

    To investigate the activity of carboplatin and cetuximab in NSCLC. This was a single arm, multicenter phase II trial, and the primary objective was response rate. The overall response rate observed was 9% (95% confidence interval [CI], 3-19), the progression-free survival was 2.9 months (95% CI, 1.9-3.6), the median overall survival was 8.2 months (95% CI, 4.9-10.5), and 1-year survival rate was 33% (95% CI, 21-45). The combination of carboplatin and cetuximab demonstrated lower activity than double agent platinum-based therapy and does not warrant further development.

  11. Experimental facility with two-phase flow and with high concentration of non-condensable gases for research and development of emergency cooling system of advanced nuclear reactors

    International Nuclear Information System (INIS)

    Macedo, Luiz Alberto; Baptista Filho, Benedito Dias

    2006-01-01

    The development of emergency cooling passive systems of advanced nuclear reactors requires the research of some relative processes to natural circulation, in two-phase flow conditions involving condensation processes in the presence of non-condensable gases. This work describes the main characteristics of the experimental facility called Bancada de Circulacao Natural (BCN), designed for natural circulation experiments in a system with a hot source, electric heater, a cold source, heat exchanger, operating with two-phase flow and with high concentration of noncondensable gas, air. The operational tests, the data acquisition system and the first experimental results in natural circulation are presented. The experiments are transitory in natural circulation considering power steps. The distribution of temperatures and the behavior of the flow and of the pressure are analyzed. The experimental facility, the instrumentation and the data acquisition system demonstrated to be adapted for the purposes of research of emergency cooling passive systems, operating with two-phase flow and with high concentration of noncondensable gases. (author)

  12. A phase II study using vinorelbine and continuous 5-fluorouracil in patients with advanced head and neck cancer

    DEFF Research Database (Denmark)

    Larsen, Susanne; Serup-Hansen, Eva; Andersen, Lisbeth J

    2007-01-01

    Seventy patients with advanced head and neck cancer were treated with vinorelbine and continuous 5-FU administered in a central venous catheter. Over all response was 36% with 9% complete responses. The most common grade 3 and 4 toxicities were stomatitis (13), infection (5), pain related...... to vinorelbine infusion (4), skin toxicity (3). Thirty one patients had grade 3 or 4 leukopenia. Treatment was complicated by venous thrombosis in the central venous catheter in one case. A majority of patients experienced dose reduction of one or both drugs or treatment delays due to toxicity. Median time...... to progression was 4.7 months and overall median survival 6.6 months. We conclude that the regimen is feasible and tolerated with moderate toxicity. Response rates and time to progression are comparable to other studies with multi agent treatment...

  13. Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Chitapanarux, Imjai; Kamnerdsupaphon, Pimkhuan; Pukanhapan, Nantaka; Tharavichitkul, Ekkasit; Vongtama, Roy

    2013-01-01

    The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III-IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3-102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3 - 4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer. (author)

  14. A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer.

    Science.gov (United States)

    Jones, Robin L; Bendell, Johanna C; Smith, David C; Diefenbach, Konstanze; Lettieri, John; Boix, Oliver; Lockhart, A Craig; O'Bryant, Cindy; Moore, Kathleen N

    2015-10-01

    To characterize the cardiovascular safety profile of regorafenib in patients with advanced cancer. Patients received regorafenib 160 mg/day for 21 days followed by a 7-day break. The primary endpoint was the change from baseline in QTcF at the regorafenib t(max) (Day 21, Cycle 1 or 2) and changes in left ventricular ejection fraction (LVEF) from baseline on Cycle 2, Day 21. Secondary objectives were pharmacokinetics, safety, anti-tumor activity and effects on electrocardiogram intervals. QT intervals were corrected using the methods of Fridericia (QTcF) and Bazett (QTcB). LVEF was assessed by multigated acquisition scanning. Fifty-three patients were enrolled, and all received at least one dose of regorafenib 160 mg. Twenty-five patients received regorafenib for 21 days without dose reduction. The mean change from baseline in QTcF at t(max) was (-)2 ms (90 % CI -8, 3). No patient experienced a change from baseline in QTcF > 60 ms, and two had QTcF changes between 30 and 60 ms. No patient had a QTcF or QTcB > 480 ms. In 27 patients who received at least 80 mg of regorafenib, the mean change from baseline in LVEF% ± SD was 1.7 ± 7.8. In 14 patients without a dose reduction, the mean change from baseline in LVEF% was (-)0.1 ± 8.6 at Cycle 2, Day 21. Four patients experienced a LVEF decrease between 10 and 20 %. The effects of regorafenib on the QT/QTc interval and LVEF were modest and unlikely to be of clinical significance in the setting of advanced cancer therapy.

  15. Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma

    International Nuclear Information System (INIS)

    Delius, Stefan von; Lersch, Christian; Schulte-Frohlinde, Ewert; Mayr, Martina; Schmid, Roland M; Eckel, Florian

    2005-01-01

    Patients with advanced gallbladder and biliary tract carcinoma face a dismal prognosis, as no effective palliative chemotherapy exists. The antitumor effect of gemcitabine is schedule-dependent rather than dose-dependent. We evaluated the activity of a prolonged infusion of gemcitabine in advanced gallbladder and biliary tract carcinomas. Nineteen consecutive eligible patients were enrolled. All patients were required to have histologically confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours at a dose of 100 mg/m 2 on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. Tumor response was evaluated every second course by computed tomography (CT) scans. Eighteen patients were evaluable for response. A total of 89 cycles of therapy were administered. One partial response was observed (6%; 95% confidence interval (CI): 0–27%) and ten additional patients had stable disease for at least two months (disease control rate 61%; 95% CI: 36–83%). The therapy was well tolerated, with moderate myelosuppression as the main toxicity. The median time to tumor progression and median overall survival was 3.6 months (95% CI 2.6–4.6 months) and 7.5 months (95% CI 6.5–8.5 months), respectively. Weekly 24-hour gemcitabine at a dose of 100 mg/m 2 is well tolerated. There was a relatively high rate of disease control for a median duration of 5.3 months (range 2.8–18.8 months). However, the objective response rate of this regimen in gallbladder and biliary tract carcinomas was limited

  16. Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer.

    Science.gov (United States)

    Muro, Kei; Oh, Sang Cheul; Shimada, Yasuhiro; Lee, Keun-Wook; Yen, Chia-Jui; Chao, Yee; Cho, Jae Yong; Cheng, Rebecca; Carlesi, Roberto; Chandrawansa, Kumari; Orlando, Mauro; Ohtsu, Atsushi

    2016-03-01

    East Asia has higher gastric cancer incidence and mortality rates than other regions. We present a subgroup analysis of East Asians in the positive study RAINBOW. Patients with advanced gastric or gastroesophageal junction adenocarcinoma previously treated with platinum and fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Of 665 intention-to-treat patients, 223 were East Asian. Median overall survival was 12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus paclitaxel (hazard ratio: 0.986, 95% confidence interval: 0.727-1.337, P = 0.929). Median progression-free survival was 5.5 months for ramucirumab plus paclitaxel and 2.8 months for placebo plus paclitaxel (hazard ratio: 0.628, 95% confidence interval: 0.473-0.834, P = 0.001). Objective response rates were 34% for ramucirumab plus paclitaxel and 20% for placebo plus paclitaxel. Grade ≥ 3 neutropenia (60% vs 28%) and leukopenia (34% vs 13%) were higher for ramucirumab plus paclitaxel. The rate of febrile neutropenia was low (4% vs 4%). Special interest adverse events included any grade bleeding/hemorrhage (55% vs 25%), proteinuria (27% vs 7%), and hypertension (22% vs 2%). Ramucirumab plus paclitaxel significantly improves progression-free survival and response rate, with prolonged median overall survival and an acceptable safety profile in East Asians with advanced gastric cancer. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Phase II Study of Chemoradiotherapy With S-1 and Low-Dose Cisplatin for Inoperable Advanced Gastric Cancer

    International Nuclear Information System (INIS)

    Saikawa, Yoshiro; Kubota, Tetsuro; Kumagai, Koshi; Nakamura, Rieko; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki; Kitagawa, Yuko

    2008-01-01

    Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions

  18. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  19. Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

    Science.gov (United States)

    Estlin, E. J.; Lashford, L.; Ablett, S.; Price, L.; Gowing, R.; Gholkar, A.; Kohler, J.; Lewis, I. J.; Morland, B.; Pinkerton, C. R.; Stevens, M. C.; Mott, M.; Stevens, R.; Newell, D. R.; Walker, D.; Dicks-Mireaux, C.; McDowell, H.; Reidenberg, P.; Statkevich, P.; Marco, A.; Batra, V.; Dugan, M.; Pearson, A. D.

    1998-01-01

    A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted. Images Figure 5 p658-b Figure 6 p659-b PMID:9744506

  20. Advanced analytical method of nereistoxin using mixed-mode cationic exchange solid-phase extraction and GC/MS.

    Science.gov (United States)

    Park, Yujin; Choe, Sanggil; Lee, Heesang; Jo, Jiyeong; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Jung, Jee H

    2015-07-01

    Nereistoxin(NTX) was originated from a marine annelid worm Lumbriconereis heteropoda and its analogue pesticides including cartap, bensultap, thiocyclam and thiobensultap have been commonly used in agriculture, because of their low toxicity and high insecticidal activity. However, NTX has been reported about its inhibitory neuro toxicity in human and animal body, by blocking nicotinic acetylcholine receptor and it cause significant neuromuscular toxicity, resulting in respiratory failure. We developed a new method to determine NTX in biological fluid. The method involves mixed-mode cationic exchange based solid phase extraction and gas chromatography/mass spectrometry for final identification and quantitative analysis. The limit of detection and recovery were substantially better than those of other methods using liquid-liquid extraction or headspace solid phase microextraction. The good recoveries (97±14%) in blood samples were obtained and calibration curves over the range 0.05-20 mg/L have R2 values greater than 0.99. The developed method was applied to a fatal case of cartap intoxication of 74 years old woman who ingested cartap hydrochloride for suicide. Cartap and NTX were detected from postmortem specimens and the cause of the death was ruled to be nereistoxin intoxication. The concentrations of NTX were 2.58 mg/L, 3.36 mg/L and 1479.7 mg/L in heart, femoral blood and stomach liquid content, respectively. The heart blood/femoral blood ratio of NTX was 0.76. Copyright © 2015. Published by Elsevier Ireland Ltd.

  1. Advanced Recombinant Manganese Peroxidase for Biosynthesis of Lignin Bioproducts, Phase I Final Report, STTR Grant #: DE-SC0007503.

    Energy Technology Data Exchange (ETDEWEB)

    Beatty, Christopher; Kitner, Joshua; Lajoie, Curtis; McClain, Sean; Potochnik, Steve

    2012-12-13

    The core purpose of this Phase I STTR was to evaluate the feasibility of a new method of producing a recombinant version of manganese peroxidase (MnP) enzyme. MnP is a potentially valuable enzyme for producing high value lignin products and also for industrial de-coloring operations such as biobleaching of pulp and color removal from textile dye effluents. This lignin-modifying enzyme is produced in small amounts by the native host, a white rot fungus. Previous work by Oregon State University developed a secreted recombinant version of the enzyme in the yeast Pichia pastoris. Unfortunately, the expression is barely moderate and the enzyme is heavily glycosylated, which inhibits purification. In this work, the gene for the enzyme is given a tag which targets production of the enzyme to the peroxisome. This is a promising approach since this location is also where heme and hydrogen peroxide are sequestered, which are both necessary cofactors for MnP. More than ten recombinant strains were constructed, verified, and expressed in the Pichia system. Constitutive (GAP) and methanol-induced promoters (AOX) were tried for peroxisomal targeted, cytosolic, and secreted versions of MnP. Only the secreted strains showed activity. The amount of expression was not significantly changed. The degree of glycosylation was lessened using the AOX (methanol) promotoer, but the resulting enzyme was still not able to be purified using immobilized metal affinity chromatography. Additional work beyond the scope of the defined Phase I project was undertaken to construct, verify, and express Pichia strains that mutated the MnP glycosylation sites to inhibit this process. These strains did not show significant activity. The cause is not known, but it is possible that these sites are important to the structure of the enzyme. Also beyond the scope proposed for our Phase I STTR, the team collaborated with AbSci, a startup with a new E. coli based expression system focused on the production of

  2. Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

    Science.gov (United States)

    West, Howard L; Moon, James; Wozniak, Antoinette J; Mack, Philip; Hirsch, Fred R; Bury, Martin J; Kwong, Myron; Nguyen, Dorothy D; Moore, Dennis F; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R

    2018-01-01

    Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Johnson, Faye M.; Garden, Adam S.; Palmer, J. Lynn; Shin, Dong M.; Morrison, William; Papadimitrakopoulou, Vassiliki; Khuri, Fadlo; Clayman, Gary; Goepfert, Helmuth; Ang, K. Kian; Hong, Waun K.; Glisson, Bonnie S.

    2005-01-01

    Purpose: Local recurrence is the most common site of failure for locally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant cisplatin/5-fluorouracil (PF) and definitive radiation at our center. Based on this, we studied the addition of chemotherapy during the boost phase of radiation after neoadjuvant PF for advanced T-stage (T3-T4) NPC. This strategy was based on theoretical radiosensitization with chemotherapy during accelerated repopulation of the tumor with relatively radioresistant clonogens. Methods and Materials: Three cycles of neoadjuvant PF was followed by conventionally fractionated radiation with additional PF during the boost portion of the radiation course. An initial Phase I study was done to establish the maximum tolerated dose of concurrent PF. Results: Forty-four patients were enrolled. Six patients in Phase I defined the MTD for concurrent PF as: cisplatin 10 mg/m 2 /day and PF 320 mg/m 2 /day, on Days 1-5 during Weeks 6 and 7 of radiation therapy based on dose-limiting toxicities of mucositis, neutropenia, and thrombocytopenia. Forty-one patients were treated with concurrent therapy per protocol: complete, partial, and minor responses were seen in 23, 16, and 2 patients, respectively. Progression-free and overall survival rates at 5 years were 55% (95% CI, 41-75%) and 66% (95% CI, 52-85%), respectively. Seven of 11 tumor-related deaths were due to local recurrence. Nine of 10 patients with local recurrence had T4-stage disease at presentation. Local control of T4 disease was achieved in 74% of patients overall, and in 25% (1/4) with World Health Organization (WHO) type 1, 76% (16/21) with WHO type 2, and 90% (9/10) with WHO type 3 histology. Common toxicities included mucositis, dermatitis, fatigue, vomiting, and weight loss. Conclusions: This regimen was feasible and associated with promising overall survival. Local recurrence remains the major reason for treatment failure in advanced T-stage NPC, especially WHO types 1 and 2

  4. Advanced temperature measurement system for the US glass industry melt tanks and delivery system. Phase 1 [final] report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    Improved temperature measurement in the melting and delivery systems of the glass making process will aid in energy conservation. The ``Needs Analysis`` survey found the greatest problem was the inability to identify in situ decalibration (drift). Phase I objectives are: a more rugged reliable sensor; high quality inner protective sheath; improved data transmission hardened to the melt tank environs; a system that reduces or eliminates drift; and an improved outer protection sheath. Results show that 4 of the 5 problem areas have been resolved; with the help of the Univ. of Missouri-Rolla`s materials group, the fifth may be solvable. The major identified problem, the inability to identify in-situ drift has been solved.

  5. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Ying G

    2013-01-01

    Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

  6. A phase I/II study of gemcitabine-concurrent proton radiotherapy for locally advanced pancreatic cancer without distant metastasis

    International Nuclear Information System (INIS)

    Terashima, Kazuki; Demizu, Yusuke; Hashimoto, Naoki; Jin, Dongcun; Mima, Masayuki; Fujii, Osamu; Niwa, Yasue; Takatori, Kento; Kitajima, Naoto; Sirakawa, Sachiyo; Yonson, Ku; Hishikawa, Yoshio; Abe, Mitsuyuki; Sasaki, Ryohei; Sugimura, Kazuro; Murakami, Masao

    2012-01-01

    Purpose: We conducted the study to assess the feasibility and efficacy of gemcitabine-concurrent proton radiotherapy (GPT) for locally advanced pancreatic cancer (LAPC). Materials and methods: Of all 50 patients who participated in the study, 5 patients with gastrointestinal (GI)-adjacent LAPC were enrolled in P-1 (50 Gy equivalent [GyE] in 25 fractions) and 5 patients with non-GI-adjacent LAPC in P-2 (70.2 GyE in 26 fractions), and 40 patients with LAPC regardless of GI-adjacency in P-3 (67.5 GyE in 25 fractions using the field-within-a-field technique). In every protocol, gemcitabine (800 mg/m 2 /week for 3 weeks) was administered concurrently. Every patient received adjuvant chemotherapy including gemcitabine after GPT within the tolerable limit. Results: The median follow-up period was 12.5 months. The scheduled GPT was feasible for all except 6 patients (12%) due to acute hematologic or GI toxicities. Grade 3 or greater late gastric ulcer and hemorrhage were seen in 5 patients (10%) in P-2 and P-3. The one-year freedom from local-progression, progression-free, and overall survival rates were 81.7%, 64.3%, and 76.8%, respectively. Conclusion: GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging.

  7. Thermal hydraulic-Mechanic Integrated Simulation for Advanced Cladding Thermal Shock Fracture Analysis during Reflood Phase in LBLOCA

    Energy Technology Data Exchange (ETDEWEB)

    Son, Seong Min; Lee, You Ho; Cho, Jae Wan; Lee, Jeong Ik [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    This study suggested thermal hydraulic-mechanical integrated stress based methodology for analyzing the behavior of ATF type claddings by SiC-Duplex cladding LBLOCA simulation. Also, this paper showed that this methodology could predict real experimental result well. That concept for enhanced safety of LWR called Advanced Accident-Tolerance Fuel Cladding (ATF cladding, ATF) is researched actively. However, current nuclear fuel cladding design criteria for zircaloy cannot be apply to ATF directly because those criteria are mainly based on limiting their oxidation. So, the new methodology for ATF design criteria is necessary. In this study, stress based analysis methodology for ATF cladding design criteria is suggested. By simulating LBLOCA scenario of SiC cladding which is the one of the most promising candidate of ATF. Also we'll confirm our result briefly through comparing some facts from other experiments. This result is validating now. Some of results show good performance with 1-D failure analysis code for SiC fuel cladding that already developed and validated by Lee et al,. It will present in meeting. Furthermore, this simulation presented the possibility of understanding the behavior of cladding deeper. If designer can predict the dangerous region and the time precisely, it may be helpful for designing nuclear fuel cladding geometry and set safety criteria.

  8. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    Directory of Open Access Journals (Sweden)

    Eichbaum Michael H

    2011-01-01

    Full Text Available Abstract Background The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. Methods/design The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border, heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Discussion Intensity-modulated WAR provides

  9. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Debus, Juergen; Kieser, Meinhard; Sterzing, Florian; Krause, Sonja; Lindel, Katja; Harms, Wolfgang; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof

    2011-01-01

    The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Intensity-modulated WAR provides a new promising option in the consolidation treatment of

  10. Mockup tests of void fraction in moderator cell and two-phase thermosiphon loop of cold neutron source in China Advanced Research Reactor

    International Nuclear Information System (INIS)

    Du Shejiao; Bi Qincheng; Chen Tingkuan; Feng Quanke; Li Xiaoming

    2004-01-01

    Full-scale mockup tests were carried out using freon-113 as a working fluid to verify the design of China Advanced Research Reactor (CARR) Cold neutron Source (CNS), which is a two-phase hydrogen thermosiphon loop consisting of an annular cylindrical moderator cell, two separated hydrogen transfer tubes and a condenser. The circulation characteristics, liquid level and void fraction in the moderator cell against the variation of the heat load were studied. The density ratio and the volumetric evaporating rate of the mockup test are kept the same as those of CARR CNS. The test results show that the mockup loop can establish stable circulation and has a self-regulating characteristic. Within the moderator cell, the inner shell contains only vapor and the outer shell contains the mixture of vapor-liquid with void fraction in a certain range. (authors)

  11. A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

    2016-11-01

    This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher

  12. Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide

    International Nuclear Information System (INIS)

    Chawla, Sant P; Staddon, Arthur; Hendifar, Andrew; Messam, Conrad A; Patwardhan, Rita; Kamel, Yasser Mostafa

    2013-01-01

    The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy. Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD). Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No dose-limiting toxicities were reported. Due to slow recruitment, the study was closed prior to identifying an OBD. The most common hematologic adverse events (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, constipation, and nausea (47% each). Eleven of 12 patients who received eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 (cycle without eltrombopag). Although data are limited, safety data were consistent with the known toxicities of AI combination chemotherapy or the side effect profile of eltrombopag seen in other studies. Available data suggest a potential pre- and post-chemotherapy dosing scheme for eltrombopag when administered with AI chemotherapy, and support further investigation of eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia

  13. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    Energy Technology Data Exchange (ETDEWEB)

    Swisher, Stephen G., E-mail: sswisher@mdanderson.org [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn A. [Headquarters, Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko U. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Wu, Tsung T. [Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Konski, Andre A. [Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Willett, Christopher G. [Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  14. Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

    Science.gov (United States)

    Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

    2018-05-01

    Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

  15. Phase mixing of transverse oscillations in the linear and nonlinear regimes for IFR relativistic electron beam propagation

    International Nuclear Information System (INIS)

    Shokair, I.R.

    1991-01-01

    Phase mixing of transverse oscillations changes the nature of the ion hose instability from an absolute to a convective instability. The stronger the phase mixing, the faster an electron beam reaches equilibrium with the guiding ion channel. This is important for long distance propagation of relativistic electron beams where it is desired that transverse oscillations phase mix within a few betatron wavelengths of injection and subsequently an equilibrium is reached with no further beam emittance growth. In the linear regime phase mixing is well understood and results in asymptotic decay of transverse oscillations as 1/Z 2 for a Gaussian beam and channel system, Z being the axial distance measured in betatron wavelengths. In the nonlinear regime (which is likely mode of propagation for long pulse beams) results of the spread mass model indicate that phase mixing is considerably weaker than in the regime. In this paper we consider this problem of phase mixing in the nonlinear regime. Results of the spread mass model will be shown along with a simple analysis of phase mixing for multiple oscillator models. Particle simulations also indicate that phase mixing is weaker in nonlinear regime than in the linear regime. These results will also be shown. 3 refs., 4 figs

  16. [Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

    Science.gov (United States)

    Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

    2015-09-01

    To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in

  17. Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

    Science.gov (United States)

    Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

    2010-07-01

    Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

  18. Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Ho; Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Yangsoon; Kim, Jihun [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jeong Eun; Kim, Kyu-pyo; Kim, Sun Young [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Jin-hong; Kim, Jong Hoon [Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, In Ja; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon [Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-10-01

    Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluated in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.

  19. Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Maurel, Joan; Martin-Richard, Marta; Conill, Carlos; Sanchez, Marcelo; Petriz, Lourdes; Gines, Angels; Miquel, Rosa; Gallego, Rosa; Cajal, Rosana; Ayuso, Carmen; Navarro, Salvador; Marmol, Maribel; Nadal, Cristina; Auge, Josep Maria; Fernandez-Cruz, Laureano; Gascon, Pere

    2006-01-01

    Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm 3 of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m 2 /day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC

  20. Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

    International Nuclear Information System (INIS)

    Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seok Ah; Lee, Keun Seok; Yun, Tak; Jeong, Seung-Yong; Choi, Hyo Seong; Lim, Seok-Byung; Chang, Hee Jin; Jung, Kyung Hae

    2011-01-01

    Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m 2 1 week before radiotherapy, and then cetuximab 250 mg/m 2 /week, irinotecan 40 mg/m 2 /week for 5 consecutive weeks and capecitabine 1,650 mg/m 2 /day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

  1. The US Advanced Liquid Metal Reactor and the Fast Flux Test Facility Phase IIA passive safety tests

    International Nuclear Information System (INIS)

    Shen, P.K.; Harris, R.A.; Campbell, L.R.; Dautel, W.A.; Dubberley, A.E.; Gluekler, E.L.

    1992-07-01

    This report discusses the safety approach of the Advanced Liquid Metal reactor program, sponsored by the US Department of Energy, which relies upon passive reactor responses to off-normal condition to limit power and temperature excursions to levels that allow safety margins. Gas expansion modules (GEM) have included in the design to provide negative reactivity to enhance these margins in the extremely unlikely event that pumping power is lost and the highly reliable scram system fails to operate. The feasibility and beneficial features of these devices were first demonstrated in the core of the Fast Flux Test Facility (FFTF) in 1986. Preapplication safety evaluations by the US Nuclear Regulatory Commission have identified areas that must be addressed if these devices are to be relied on. One of these areas is the response of the reactor when it is critical and the pumps are turned on, resulting in positive reactivity being added to the core. Tests to examine such transients have been performed as part of the continuing FFTF program to confirm the passive safety characteristics of liquid metal reactors (LMR). The primary tests consisted of starting the main coolant pumps, which forced sodium coolant into the GEMS, decreasing neutron leakage and adding positive reactivity. The resulting transients were shown to be benign and easily mitigated by the reactivity feedbacks inherent in the FFTF and all LMRs. Steady-state auxiliary tests of the GEM and feedback reactivity worths accurately predicted the transient results. The auxiliary GEM worth tests also demonstrated that the worth can be determined at a subcritical state, which allows for a verification of the GEM's availability prior to ascending to power

  2. Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chiorean, E. Gabriela, E-mail: gchiorea@uw.edu [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Department of Medicine, University of Washington, Seattle, Washington (United States); Schneider, Bryan P. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Akisik, Fatih M. [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Perkins, Susan M. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); Anderson, Stephen [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Johnson, Cynthia S. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); DeWitt, John [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Deluca, Jill [Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Bu, Guixue [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Shahda, Safi; Loehrer, Patrick J. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Sandrasegaran, Kumar [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Cardenes, Higinia R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States)

    2014-06-01

    Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

  3. Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Gu, Lin [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Dunphy, Frank R.; Ready, Neal E. [Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States)

    2015-12-01

    Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

  4. Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma.

    Science.gov (United States)

    Konner, Jason; Grisham, Rachel N; Park, Jae; O'Connor, Owen A; Cropp, Gillian; Johnson, Robert; Hannah, Alison L; Hensley, Martee L; Sabbatini, Paul; Mironov, Svetlana; Miranov, Svetlana; Danishefsky, Samuel; Hyman, David; Spriggs, David R; Dupont, Jakob; Aghajanian, Carol

    2012-12-01

    To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2). Thirty-two patients were enrolled, and twenty-nine completed ≥1 cycle of therapy. Dose limiting toxicity [DLT] was observed at 120 mg/m(2). PK data were linear from 16 to 100 mg/m(2), with proportional increases in mean C(max) and AUC(tot) as a function of dose. Full PK analysis (mean ± SD) at 100 mg/m(2) revealed the following: half-life (t (½)) = 9.1 ± 2.2 h; volume of distribution (V(z)) = 119 ± 41 L/m(2); clearance (CL) = 9.3 ± 3.2 L/h/m(2). MTBF (n = 9) was seen in 40% of PBMCs within 1 h and in 15% of PBMC at 24-hours post infusion at 100 mg/m(2). Tumor shrinkage (n = 2, lymphoma), stable disease >3 months (n = 5, renal, prostate, oropharynx, cholangiocarcinoma, and Hodgkin lymphoma), and tumor marker reductions (n = 1, colorectal cancer/CEA) were observed. KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m(2) weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862.

  5. Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

    2014-01-01

    Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m 2 intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m 2 intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K trans in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival

  6. Probing Phase Transformations and Microstructural Evolutions at the Small Scales: Synchrotron X-ray Microdiffraction for Advanced Applications in [Phase 3 Memory,] 3D IC (Integrated Circuits) and Solar PV (Photovoltaic) Devices

    Energy Technology Data Exchange (ETDEWEB)

    Radchenko, I. [Singapore Univ. of Technology and Design (SUTD) (Singapore); Tippabhotla, S. K. [Singapore Univ. of Technology and Design (SUTD) (Singapore); Tamura, N. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Budiman, A. S. [Singapore Univ. of Technology and Design (SUTD) (Singapore)

    2016-10-21

    Synchrotron x-ray microdiffraction (μXRD) allows characterization of a crystalline material in small, localized volumes. Phase composition, crystal orientation and strain can all be probed in few-second time scales. Crystalline changes over a large areas can be also probed in a reasonable amount of time with submicron spatial resolution. However, despite all the listed capabilities, μXRD is mostly used to study pure materials but its application in actual device characterization is rather limited. This article will explore the recent developments of the μXRD technique illustrated with its advanced applications in microelectronic devices and solar photovoltaic systems. Application of μXRD in microelectronics will be illustrated by studying stress and microstructure evolution in Cu TSV (through silicon via) during and after annealing. Here, the approach allowing study of the microstructural evolution in the solder joint of crystalline Si solar cells due to thermal cycling will be also demonstrated.

  7. An inflammation based score can optimize the selection of patients with advanced cancer considered for early phase clinical trials.

    Directory of Open Access Journals (Sweden)

    David J Pinato

    Full Text Available Adequate organ function and good performance status (PS are common eligibility criteria for phase I trials. As inflammation is pathogenic and prognostic in cancer we investigated the prognostic performance of inflammation-based indices including the neutrophil (NLR and platelet to lymphocyte ratio (PLR.We studied inflammatory scores in 118 unselected referrals. NLR normalization was recalculated at disease reassessment. Each variable was assessed for progression-free (PFS and overall survival (OS on uni- and multivariate analyses and tested for 90 days survival (90DS prediction using receiving operator curves (ROC.We included 118 patients with median OS 4.4 months, 23% PS>1. LDH≥450 and NLR≥5 were multivariate predictors of OS (p<0.001. NLR normalization predicted for longer OS (p<0.001 and PFS (p<0.05. PS and NLR ranked as most accurate predictors of both 90DS with area under ROC values of 0.66 and 0.64, and OS with c-score of 0.69 and 0.60. The combination of NLR+PS increased prognostic accuracy to 0.72. The NLR was externally validated in a cohort of 126 subjects.We identified the NLR as a validated and objective index to improve patient selection for experimental therapies, with its normalization following treatment predicting for a survival benefit of 7 months. Prospective validation of the NLR is warranted.

  8. Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

    Science.gov (United States)

    Michael, M; Chander, S; McKendrick, J; MacKay, J R; Steel, M; Hicks, R; Heriot, A; Leong, T; Cooray, P; Jefford, M; Zalcberg, J; Bressel, M; McClure, B; Ngan, S Y

    2014-11-11

    Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

  9. Advances in liquid phase soft-x-ray photoemission spectroscopy: A new experimental setup at BESSY II

    Science.gov (United States)

    Seidel, Robert; Pohl, Marvin N.; Ali, Hebatallah; Winter, Bernd; Aziz, Emad F.

    2017-07-01

    A state-of-the-art experimental setup for soft X-ray photo- and Auger-electron spectroscopy from liquid phase has been built for operation at the synchrotron-light facility BESSY II, Berlin. The experimental station is named SOL3, which is derived from solid, solution, and solar, and refers to the aim of studying solid-liquid interfaces, optionally irradiated by photons in the solar spectrum. SOL3 is equipped with a high-transmission hemispherical electron analyzer for detecting electrons emitted from small molecular aggregates, nanoparticles, or biochemical molecules and their components in (aqueous) solutions, either in vacuum or in an ambient pressure environment. In addition to conventional energy-resolved electron detection, SOL3 enables detection of electron angular distributions by the combination of a ±11° acceptance angle of the electron analyzer and a rotation of the analyzer in the polarization plane of the incoming synchrotron-light beam. The present manuscript describes the technical features of SOL3, and we also report the very first measurements of soft-X-ray photoemission spectra from a liquid microjet of neat liquid water and of TiO2-nanoparticle aqueous solution obtained with this new setup, highlighting the necessity for state-of-the-art electron detection.

  10. Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma

    International Nuclear Information System (INIS)

    Mayr, Martina; Becker, Karen; Schulte, Nadine; Belle, Sebastian; Hofheinz, Ralf; Krause, Annekatrin; Schmid, Roland M; Röcken, Christoph; Ebert, Matthias P

    2012-01-01

    Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. This phase I study evaluated dose limiting toxicity (DLT) of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m 2 d1 q 3w)/ capecitabine (1250 mg/m 2 bid d1-14 q 21) or cisplatin (50 mg/m 2 d1 q 2w)/ 5-fluoruracil (2 g/m 2 d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510

  11. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma.

    Science.gov (United States)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F; George, Saby; Hammers, Hans J; Srinivas, Sandhya; Tykodi, Scott S; Sosman, Jeffrey A; Procopio, Giuseppe; Plimack, Elizabeth R; Castellano, Daniel; Gurney, Howard; Donskov, Frede; Peltola, Katriina; Wagstaff, John; Gauler, Thomas C; Ueda, Takeshi; Zhao, Huanyu; Waxman, Ian M; Motzer, Robert J

    2017-12-01

    The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  12. Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trail

    International Nuclear Information System (INIS)

    Meng, Xue; Wang, Jianhua; Sun, Xindong; Wang, Lvhua; Ye, Ming; Feng, Pingbo; Zhu, Guangying; Lu, You; Han, Chun; Zhu, Shuchai; Liao, Zhongxing; Yu, Jinming

    2013-01-01

    Background and purpose: This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). Material and methods: Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400 mg/m 2 loading dose on day 1; and on day 1 of the 2nd–7th weeks: cetuximab 250 mg/m 2 , paclitaxel 45 mg/m 2 , and cisplatin 20 mg/m 2 , concurrent with 59.4 Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status. Results: Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples. Conclusions: Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate

  13. Analytical and experimental evaluation of joining silicon carbide to silicon carbide and silicon nitride to silicon nitride for advanced heat engine applications Phase 2. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Sundberg, G.J.; Vartabedian, A.M.; Wade, J.A.; White, C.S. [Norton Co., Northboro, MA (United States). Advanced Ceramics Div.

    1994-10-01

    The purpose of joining, Phase 2 was to develop joining technologies for HIP`ed Si{sub 3}N{sub 4} with 4wt% Y{sub 2}O{sub 3} (NCX-5101) and for a siliconized SiC (NT230) for various geometries including: butt joins, curved joins and shaft to disk joins. In addition, more extensive mechanical characterization of silicon nitride joins to enhance the predictive capabilities of the analytical/numerical models for structural components in advanced heat engines was provided. Mechanical evaluation were performed by: flexure strength at 22 C and 1,370 C, stress rupture at 1,370 C, high temperature creep, 22 C tensile testing and spin tests. While the silicon nitride joins were produced with sufficient integrity for many applications, the lower join strength would limit its use in the more severe structural applications. Thus, the silicon carbide join quality was deemed unsatisfactory to advance to more complex, curved geometries. The silicon carbide joining methods covered within this contract, although not entirely successful, have emphasized the need to focus future efforts upon ways to obtain a homogeneous, well sintered parent/join interface prior to siliconization. In conclusion, the improved definition of the silicon carbide joining problem obtained by efforts during this contract have provided avenues for future work that could successfully obtain heat engine quality joins.

  14. The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies

    Directory of Open Access Journals (Sweden)

    Patrizia Popoli

    2011-01-01

    Full Text Available Advanced therapy medicinal products (ATMP can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP for production, good laboratory practice (GLP for non clinical safety studies and good clinical practice (GCP for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

  15. The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies.

    Science.gov (United States)

    Popoli, Patrizia; Cometa, Maria Francesca; Fabi, Fulvia; Meneguz, Annarita

    2011-01-01

    Advanced therapy medicinal products (ATMP) can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP) for production, good laboratory practice (GLP) for non clinical safety studies and good clinical practice (GCP) for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues) is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

  16. Preoperative Chemoradiation With Irinotecan and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: Long-Term Results of a Phase II Study

    International Nuclear Information System (INIS)

    Hong, Yong Sang; Kim, Dae Yong; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Jeong, Jun Yong; Sohn, Dae Kyung; Kim, Dae-Hyun; Chang, Hee Jin; Park, Jae-Gahb; Jung, Kyung Hae

    2011-01-01

    Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m 2 of irinotecan per week for 5 consecutive weeks and 1,650 mg/m 2 of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.

  17. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

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    Greten, Tim F; Bruix, Jordi; Forner, Alejandro; Korangy, Firouzeh; N'Kontchou, Gisele; Barget, Nathalie; Ayuso, Carmen; Ormandy, Lars A; Manns, Michael P; Beaugrand, Michel

    2010-01-01

    The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. 40 patients with advanced HCC were treated with 300 mg/m 2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4 + CD25 + Foxp3 + regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. NCT00444782

  18. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

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    Ayuso Carmen

    2010-05-01

    Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

  19. A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

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    Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.; Bergsland, Emily K.; Dito, Elizabeth R.N.; Schillinger, Brian R.N.; Tempero, Margaret A.

    2007-01-01

    Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m 2 at 10 mg/m 2 /min) plus cisplatin 20 mg/m 2 on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m 2 orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation

  20. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

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    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Oh, Jae Hwan [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Jong Hoon; Jang, Hong Seok [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jun-Gi [Department of Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Myung Ah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Gwang-Ju (Korea, Republic of)

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.