Influence of the Characteristics of the STM-tip on the Electroluminescence Spectra

We analyze the influence of the characteristics of the STM-tip (applied voltage, tip radius) on the electroluminescence spectra from an STM-tip-induced quantum dot taking into account the many-body effects. We find that positions of electroluminescence peaks, attributed to the electron-hole recombination in the quantum dot, are very sensitive to the shape and size of the confinement potential as determined by the tip radius and the applied voltage. A critical value of the tip radius is found, at which the luminescence peak positions as a function of the tip radius manifest a transition from decreasing behavior for smaller radii to increasing behavior for larger radii. We find that this critical value of the tip radius is related to the confinement in the lateral and normal direction.Comment: 15 pages, 5 figure

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

Highly ionized Fe X-ray lines at energies 7.7-8.6 keV

Fe XXV lines at 1.85 A (6.70 keV) and nearby Fe XXIV satellites have been widely used for determining the temperature of the hottest parts of solar flare and tokamak plasmas, though the spectral region is crowded and the lines are blended during flare impulsive stages. The aim of this work is to show that similarly excited Fe lines in the 7.7--8.6 keV (1.44--1.61 A) region have the same diagnostic capability with the advantage of not being so crowded. Spectra in the 7.7--8.6 keV range are synthesized using the CHIANTI spectral package for conditions (temperature, turbulent velocities) appropriate to solar flares. The calculated spectra show that the Fe lines in the 7.7--8.6 keV are well separated even when turbulent velocities are present, and Fe XXIV/Fe XXV line ratios should therefore provide valuable tools for diagnosing flares and tokamak plasmas. It is concluded that Fe lines in the 7.7--8.6 keV range are ideal for the measurement of flare temperature and for detecting the presence of low-energy nonthermal electrons present at flare impulsive stages. An indication of what type of instruments to observe this region is given.Comment: 6 pages, 7 figures. Accepted for publication in Astronomy and Astrophysic

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

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

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

Oxidation behavior of molybdenum silicides and their composites

A key materials issue associated with the future of high-temperature structural silicides is the resistance of these materials to oxidation at low temperatures. Oxidation tests were conducted on Mo-based silicides over a wide temperature range to evaluate the effects of alloy composition and temperature on the protective scaling characteristics and testing regime for the materials. The study included Mo{sub 5}Si{sub 3} alloys that contained several concentrations of B. In addition, oxidation characteristics of MoSi{sub 2}-Si{sub 3}N{sub 4} composites that contained 20--80 vol.% Si{sub 3}N{sub 4} were evaluated at 500--1,400 C

Directed Evolution Generates a Novel Oncolytic Virus for the Treatment of Colon Cancer

Background Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term “Directed Evolution” for creating highly potent oncolytic viruses. Methodology/Principal Findings Taking the “Directed Evolution” approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2–3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent. Conclusions/Significance Using the “Directed Evolution” methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies

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

Directed adenovirus evolution using engineered mutator viral polymerases

Adenoviruses (Ads) are the most frequently used viruses for oncolytic and gene therapy purposes. Most Ad-based vectors have been generated through rational design. Although this led to significant vector improvements, it is often hampered by an insufficient understanding of Ad’s intricate functions and interactions. Here, to evade this issue, we adopted a novel, mutator Ad polymerase-based, ‘accelerated-evolution’ approach that can serve as general method to generate or optimize adenoviral vectors. First, we site specifically substituted Ad polymerase residues located in either the nucleotide binding pocket or the exonuclease domain. This yielded several polymerase mutants that, while fully supportive of viral replication, increased Ad’s intrinsic mutation rate. Mutator activities of these mutants were revealed by performing deep sequencing on pools of replicated viruses. The strongest identified mutators carried replacements of residues implicated in ssDNA binding at the exonuclease active site. Next, we exploited these mutators to generate the genetic diversity required for directed Ad evolution. Using this new forward genetics approach, we isolated viral mutants with improved cytolytic activity. These mutants revealed a common mutation in a splice acceptor site preceding the gene for the adenovirus death protein (ADP). Accordingly, the isolated viruses showed high and untimely expression of ADP, correlating with a severe deregulation of E3 transcript splicing