A phase I study of the p-glycoprotein antagonist Tarquidar in combination with Vinorelbine.

P-glycoprotein (Pgp) antagonists have had unpredictable pharmacokinetic interactions requiring reductions of chemotherapy. We report a phase I study using tariquidar (XR9576), a potent Pgp antagonist, in combination with vinorelbine. EXPERIMENTAL DESIGN: Patients first received tariquidar alone to assess effects on the accumulation of (99m)Tc-sestamibi in tumor and normal organs and rhodamine efflux from CD56+ mononuclear cells. In the first cycle, vinorelbine pharmacokinetics was monitored after the day 1 and 8 doses without or with tariquidar. In subsequent cycles, vinorelbine was administered with tariquidar. Tariquidar pharmacokinetics was studied alone and with vinorelbine. RESULTS: Twenty-six patients were enrolled. Vinorelbine 20 mg/m(2) on day 1 and 8 was identified as the maximum tolerated dose (neutropenia). Nonhematologic grade 3/4 toxicities in 77 cycles included the following: abdominal pain (4 cycles), anorexia (2), constipation (2), fatigue (3), myalgia (2), pain (4) and dehydration, depression, diarrhea, ileus, nausea, and vomiting, (all once). A 150-mg dose of tariquidar: (1) reduced liver (99m)Tc-sestamibi clearance consistent with inhibition of liver Pgp; (2) increased (99m)Tc-sestamibi retention in a majority of tumor masses visible by (99m)Tc-sestamibi; and (3) blocked Pgp-mediated rhodamine efflux from CD56+ cells over the 48 hours examined. Tariquidar had no effects on vinorelbine pharmacokinetics. Vinorelbine had no effect on tariquidar pharmacokinetics. One patient with breast cancer had a minor response, and one with renal carcinoma had a partial remission. CONCLUSIONS: Tariquidar is a potent Pgp antagonist, without significant side effects and much less pharmacokinetic interaction than previous Pgp antagonists. Tariquidar offers the potential to increase drug exposure in drug-resistant cancers.

Large molecules in the envelope surrounding IRC+10216

A new chemical model of the circumstellar envelope surrounding the carbon-rich star IRC+10216 is developed that includes carbon-containing molecules with up to 23 carbon atoms. The model consists of 3851 reactions involving 407 gas-phase species. Sizeable abundances of a variety of large molecules - including carbon clusters, unsaturated hydrocarbons and cyanopolyynes - have been calculated. Negative molecular ions of chemical formulae C-n(-) and CnH- (7 less than or equal to n less than or equal to 23) exist in considerable abundance, with peak concentrations at distances from the central star somewhat greater than their neutral counterparts. The negative ions might be detected in radio emission, or even in the optical absorption of background field stars. The calculated radial distributions of the carbon-chain CnH radicals are looked at carefully and compared with interferometric observations.

Envelope-tracking-based Doherty power amplifier

From the instantaneous efficiency plot, it is observed that the conventional 2-stage Doherty power amplifier (DPA) with high upper power dynamic range (>12 dB) suffers from a substantial dip in the middle of the upper power regime, thus reducing the average efficiency. In this study, an envelope-tracking-based DPA is proposed in order to minimise this dip by adjusting the drain bias voltage of the auxiliary amplifier of the DPA proportional to the input power level.

A low-energy core-collapse supernova without a hydrogen envelope

The final fate of massive stars depends on many factors. Theory suggests that some with initial masses greater than 25 to 30 solar masses end up as Wolf-Rayet stars, which are deficient in hydrogen in their outer layers because of mass loss through strong stellar winds. The most massive of these stars have cores which may form a black hole and theory predicts that the resulting explosion of some of them produces ejecta of low kinetic energy, a faint optical luminosity and a small mass fraction of radioactive nickel. An alternative origin for low-energy supernovae is the collapse of the oxygen-neon core of a star of 7-9 solar masses. No weak, hydrogen-deficient, core-collapse supernovae have hitherto been seen. Here we report that SN 2008ha is a faint hydrogen-poor supernova. We propose that other similar events have been observed but have been misclassified as peculiar thermonuclear supernovae (sometimes labelled SN 2002cx-like events). This discovery could link these faint supernovae to some long-duration gamma-ray bursts, because extremely faint, hydrogen-stripped core-collapse supernovae have been proposed to produce such long gamma-ray bursts, the afterglows of which do not show evidence of associated supernovae.

Ion-acoustic waves in a two-electron-temperatute plasma: oblique modulation and envelope excitations

Theoretical and numerical studies are carried out for the nonlinear amplitude modulation of ion-acoustic waves propagating in an unmagnetized, collisionless, three-component plasma composed of inertial positive ions moving in a background of two thermalized electron populations. Perturbations oblique to the carrier wave propagation direction have been considered. The stability analysis, based on a nonlinear Schrodinger-type equation, shows that the wave may become unstable; the stability criteria depend on the angle theta between the modulation and propagation directions. Different types of localized excitations (envelope solitary waves) are shown to exist in qualitative agreement with satellite observations in the magnetosphere.

Finite ion temperature effects on oblique modulational stability and envelope excitations of dust-ion acoustic waves

Theoretical and numerical investigations are carried out for the amplitude modulation of dust-ion acoustic waves (DIAW) propagating in an unmagnetized weakly coupled collisionless fully ionized plasma consisting of isothermal electrons, warm ions and charged dust grains. Modulation oblique (by an angle theta) to the carrier wave propagation direction is considered. The stability analysis, based on a nonlinear Schrodinger-type equation (NLSE), exhibits a sensitivity of the instability region to the modulation angle theta, the dust concentration and the ion temperature. It is found that the ion temperature may strongly modify the wave's stability profile, in qualitative agreement with previous results, obtained for an electron-ion plasma. The effect of the ion temperature on the formation of DIAW envelope excitations (envelope solitons) is also discussed.

Electron-acoustic plasma waves: Oblique modulation and envelope solitons

Theoretical and numerical studies are presented of the amplitude modulation of electron-acoustic waves (EAWs) propagating in space plasmas whose constituents are inertial cold electrons, Boltzmann distributed hot electrons, and stationary ions. Perturbations oblique to the carrier EAW propagation direction have been considered. The stability analysis, based on a nonlinear Schrodinger equation, reveals that the EAW may become unstable; the stability criteria depend on the angle theta between the modulation and propagation directions. Different types of localized EA excitations are shown to exist.

Modulated wave packets and envelope solitary structures in complex plasmas

A theoretical study is presented of the nonlinear amplitude modulation of waves propagating in unmagnetized plasmas contaminated by charged dust particles. Distinct well-known dusty plasma modes are explicitly considered, namely, the dust-acoustic wave, the dust-ion acoustic wave, and transverse dust-lattice waves. Using a multiple-scale technique, a nonlinear Schrodinger-type equation is derived, describing the evolution of the wave amplitude. A stability analysis reveals the possibility for modulational instability to occur, possibly leading to the formation of different types of envelope-localized excitations (solitary waves), under conditions which depend on the wave dispersion laws and intrinsic dusty plasma parameters.

Nonlinear Lagrangian theory of envelope electrostatic plasma waves in a two-electron-temperature plasma

An analytical model based on Lagrangian variables is presented for the description of ion-acoustic waves propagating in an unmagnetized, collisionless, three-component plasma composed of inertial positive ions and two thermalized electron populations, characterized by different temperatures. The wave's amplitude is shown to be modulationally unstable. Different types of localized envelope electrostatic excitations are shown to exist, and their forms are analytically and numerically investigated in terms of the plasma dispersion and nonlinearity laws. These results are in qualitative agreement with satellite observations in the magnetosphere. (C) 2004 American Institute of Physics.

Envelope solitons associated with electromagnetic waves in a magnetized pair plasma

The amplitude modulation of magnetic field-aligned circularly polarized electromagnetic (CPEM) waves in a magnetized pair plasma is reexamined. The nonlinear frequency shifts include the effects of the radiation pressure driven density and compressional magnetic field perturbations as well as relativistic particle mass variations. The dynamics of the modulated CPEM wave packets is governed by a nonlinear Schrodinger equation, which has attractive and repulsive interaction potentials for fast and slow CPEM waves. The modulational stability of a constant amplitude CPEM wave is studied by deriving a nonlinear dispersion from the cubic Schrodinger equation. The fast (slow) CPEM mode is modulationally unstable (stable). Possible stationary amplitude solutions of the modulated fast (slow) CPEM mode can be represented in the form of bright and dark/gray envelope electromagnetic soliton structures. Localized envelope excitations can be associated with the microstructures in pulsar magnetospheres and in laboratory pair magnetoplasmas. (C) 2005 American Institute of Physics.

Exact theory for localized envelope modulated electrostatic wavepackets in space and dusty plasmas

Abundant evidence for the occurrence of modulated envelope plasma wave packets is provided by recent satellite missions. These excitations are characterized by a slowly varying localized envelope structure, embedding the fast carrier wave, which appears to be the result of strong modulation of the wave amplitude. This modulation may be due to parametric interactions between different modes or, simply, to the nonlinear (self-)interaction of the carrier wave. A generic exact theory is presented in this study, for the nonlinear self-modulation of known electrostatic plasma modes, by employing a collisionless fluid model. Both cold (zero-temperature) and warm fluid descriptions are discussed and the results are compared. The (moderately) nonlinear oscillation regime is investigated by applying a multiple scale technique. The calculation leads to a Nonlinear Schrodinger-type Equation (NLSE), which describes the evolution of the slowly varying wave amplitude in time and space. The NLSE admits localized envelope (solitary wave) solutions of bright(pulses) or dark- (holes, voids) type, whose characteristics (maximum amplitude, width) depend on intrinsic plasma parameters. Effects like amplitude perturbation obliqueness (with respect to the propagation direction), finite temperature and defect (dust) concentration are explicitly considered. Relevance with similar highly localized modulated wave structures observed during recent satellite missions is discussed.

Modulated electrostatic modes in pair plasmas: Modulational stability profile and envelope excitations

A pair plasma consisting of two types of ions, possessing equal masses and opposite charges, is considered. The nonlinear propagation of modulated electrostatic wave packets is studied by employing a two-fluid plasma model. Considering propagation parallel to the external magnetic field, two distinct electrostatic modes are obtained, namely a quasiacoustic lower moddfe and a Langmuir-like, as optic-type upper one, in agreement with experimental observations and theoretical predictions. Considering small yet weakly nonlinear deviations from equilibrium, and adopting a multiple-scale technique, the basic set of model equations is reduced to a nonlinear Schrodinger equation for the slowly varying electric field perturbation amplitude. The analysis reveals that the lower (acoustic) mode is stable and may propagate in the form of a dark-type envelope soliton (a void) modulating a carrier wave packet, while the upper linear mode is intrinsically unstable, and may favor the formation of bright-type envelope soliton (pulse) modulated wave packets. These results are relevant to recent observations of electrostatic waves in pair-ion (fullerene) plasmas, and also with respect to electron-positron plasma emission in pulsar magnetospheres. (c) 2006 American Institute of Physics.