Toroidal plasma rotation in the PLT tokamak with neutral-beam injection

Toroidal plasma rotation in the Princeton Large Torus, PLT, has been measured for various plasma and neutral beam injection conditions. Measurements of the plasma rotational velocities were made from Doppler shifts of appropriate spectral lines and include data from both hydrogen and deuterium beams and co- and counter-injection at several electron densities. Without injection, a small but consistent toroidal rotation exists in a direction opposite to the plasma current (counter-direction) in the plasma center but parallel to the current (co-direction) in the plasma periphery. Using these measured velocities and the plasma density and temperature gradients, radial electron fields can be determined from theory, giving E/sub r / approx. = 40 V/cm near the plasma center and E/sub r/ approx. = 10 V/cm near the plasma edge. Insertion of a local, 2.5 percent magnetic well produced no observable effect on the beam driven rotation. Modeling of the time evolution and radial distribution of the rotation allows one to deduce an effective viscosity of the order of (1 to 5) x 10/sup 4/ cm/sup 2//sec

Varieties of sawtooth behavior in TFTR plasmas

The side-viewing soft-x-ray camera on the Tokamak Fusion Test Reactor (TFTR) has made possible the observation of several different forms of sawtooth oscillation, which can be categorized according to their position in the plasma, sequence of occurrence, and patterns of associated MHD oscillation. Some insight into the plasma conditions involved can be gained by examining the waveforms in detail, along with electron temperature profiles from electron cyclotron emission measurements

Dielectronic satellite spectrum of helium-like iron (Fe XXV)

Dielectronic satellite spectra of Fe XXV near 1.8500 A have been observed from PLT (Princeton Large Torus) tokamak plasma discharges for electron temperatures in the range from 1.5 to 3 keV and an electron density of 2 x 10/sup 13/ cm/sup -3/. The electron temperature was independently determined from the electron cyclotron radiation emitted by the plasma. The quality of the spectra allows a detailed comparison with theoretical prediction, which is of importance in view of diagnostic applications

Satellite spectra for helium-like titanium. Part II

K/sup ..cap alpha../ x-ray spectra of helium-like titanium, Ti XXI, from Tokamak Fusion Test Reactor (TFTR) plasmas have been observed with a high resolution crystal spectrometer and have been used as a diagnostic of central plasma parameters. The data allow detailed comparison with recent theoretical predictions for the Ti XXI helium-like lines and the associated satellite spectrum in the wavelength range from 2.6000 to 2.6400 A. Improved values for the excitation rate coefficients of the Ti XXI resonance line, the intercombination lines and the forbidden line, and new theoretical results on the wavelengths and transition probabilities for beryllium-like satellites due to transitions of the type 1s/sup 2/ 2lnl' - 1s2p2l'' nl'' with n = 2-4 have been calculated

Replication and Virus-Induced Transcriptome of HAdV-5 in Normal Host Cells versus Cancer Cells - Differences of Relevance for Adenoviral Oncolysis

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by modulating tumor cell functions to better support viral replication

Fiber Mediated Receptor Masking in Non-Infected Bystander Cells Restricts Adenovirus Cell Killing Effect but Promotes Adenovirus Host Co-Existence

The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI), and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses

Gene therapy: the end of the rainbow?

The increased understanding of the molecular basis of oral cancer has led to expectations that correction of the genetic defects will lead to improved treatments. Nevertheless, the first clinical trials for gene therapy of oral cancer occurred 20 years ago, and routine treatment is still not available. The major difficulty is that genes are usually delivered by virus vectors whose effects are weak and temporary. Viruses that replicate would be better, and the field includes many approaches in that direction. If any of these are effective in patients, then gene therapy will become available in the next few years. Without significant advances, however, the treatment of oral cancer by gene therapy will remain as remote as the legendary pot of gold at the end of the rainbow