The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.

Overview and initial results of the very long baseline interferometry space observatory programme

High angular resolution images of extragalactic radio sources are being made with the Highly Advanced Laboratory for Communications and Astronomy (HALCA) satellite and ground-based radio telescopes as part of the Very Long Baseline Interferometry (VLBI) Space Observatory Programme (VSOP). VSOP observations at 1.6 and 5 gigahertz of the milli-arc-second-scale structure of radio quasars enable the quasar core size and the corresponding brightness temperature to be determined, and they enable the motions of jet components that are close to the core to be studied. Here, VSOP images of the gamma-ray source 1156+295, the quasar 1548+056, the ultraluminous quasar 0014+813, and the superluminal quasar 0212+735 are presented and discussed.

Subparsec-scale structure and evolution of Centaurus A (NGC5128).

We present a series of 8.4-GHz very-long-baseline radio interferometry images of the nucleus of Centaurus A (NGC5128) made with a Southern Hemisphere array, representing a 3.3-year monitoring effort. The nuclear radio jet is approximately 50 milliarcseconds in extent, or at the 3.5-megaparsec distance of NGC5128, approximately 1 parsec in length. Subluminal motion is seen and structural changes are observed on time scales shorter than 4 months. High-resolution observations at 4.8 and 8.4 GHz made in November 1992 reveal a complex morphology and allow us to unambiguously identify the self-absorbed core located at the southwestern end of the jet.

Effect of a platinum chemotherapy drug on intracellular elements during the cell cycle, using X-ray microanalysis.

Intracellular elemental concentrations were measured in the cytoplasm, nucleus and nucleolus of cultured Chinese hamster ovary (CHO) cells, using energy dispersive electron probe X-ray microanalysis and transmission electron microscopy. Synchronous CHO cell populations were analyzed at different times during the growth cycle. The elements K, P, Mg and Zn were all more concentrated in the nucleus and nucleolus than in the cytoplasm, while no specific subcellular compartmentalization was evident for the elements Na, Cl, Ca, Fe and S. Significant changes in intracellular elemental concentrations were associated with the progression of cells from G1 phase to S phase of the growth cycle. Most significant were the effects on the monovalent ions, Na, K and Cl. The effect of a second generation platinum chemotherapy agent, cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum IV (iproplatin) on intracellular elements was investigated by analyzing subcellular compartments of drug-treated synchronous CHO cell populations. Changes in intracellular elemental levels occurred, most notably in the nucleus of G1 phase cells, when a general depletion of most essential elements was evident. Attempts to analyze cells for their Pt content proved disappointing, since quantitation for Pt was not possible. However, measurement of Pt peak/background ratio yielded significant Pt peaks on analyzing lysosomes of cells treated with high concentrations of iproplatin. These Pt peaks were associated with high levels of S and Fe.

Evidence that glutathione may determine the differential cell-cycle phase toxicity of a platinum (IV) antitumor agent.

Intracellular thiol group concentrations were monitored during the cell cycle of synchronous cultured Chinese hamster ovary (CHO) cells. Cyclic fluctuations in nonprotein thiol levels were observed that correlated with a cyclic change in cellular sensitivity to the platinum-based chemotherapy drug iproplatin (CHIP). Intracellular protein-bound nonprotein disulfide concentrations were inversely related to nonprotein thiol levels. Protein-bound thiol groups varied in concentration during the cell cycle, but the cyclic pattern did not relate to changes in nonprotein thiol to disulfide groups or to cellular sensitivity to CHIP toxicity. Cultured CHO cells were depleted of intracellular glutathione (GSH) with the use of buthionine sulfoximine. These cells were significantly more sensitive to CHIP toxicity than were control cultures. In addition, although control synchronous CHO cells showed considerable differential cell-cycle phase sensitivity to treatment with CHIP, the sensitivity of GSH-depleted synchronous cells did not alter during the cell cycle.

Cell cycle phase sensitivity to cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum (IV) (CHIP).

Cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum (IV) (CHIP) is a second generation platinum coordination complex now in Phase II clinical trials. In vitro studies with Chinese Hamster Ovary cell cultures show that CHIP is a phase-sensitive drug, being most cytotoxic to cells in early G1 phase and least toxic to late S and G2 phase cells. The dose-modifying factor between the drug sensitivity of cells treated in G1 and in late S phase is 1.6. These findings and their clinical significance are discussed with respect to the phase sensitivity of other cytotoxic agents.