High-resolution Keck I spectroscopy of Galactic halo post-asymptotic giant branch stars

Absolute and differential abundance analyses have been performed from high-resolution, high signal-to-noise ratio optical (Keck I) spectra for three evolved Galactic halo stars, namely PG 1704 + 222, HD 341617 and LSIV -0401. Their derived atmospheric parameters indicate that all three objects are undergoing a post-asymptotic giant branch (post-AGB) phase of evolution. A differential abundance analysis reveals HD 341617 as having a mild carbon deficiency of 0.74 dex, possibly due to the star having evolved off the AGB before the onset of the third dredge-up. Although such carbon underabundances are typical of hot post-AGB objects, the same trend is not observed in PG 1704 + 222, where the carbon abundance is found to be consistent with those derived for nitrogen and oxygen. Hence, a dredge-up scenario need not be invoked to explain the chemical composition of PG 1704 + 222. For LSIV -0401 no iron deficiency is apparent relative to magnesium and silicon, and hence a gas- dust separation event in the AGB progenitor need not be invoked for this star.

Biodegradation and Rhodococcus--masters of catabolic versatility.

The genus Rhodococcus is a very diverse group of bacteria that possesses the ability to degrade a large number of organic compounds, including some of the most difficult compounds with regard to recalcitrance and toxicity. They achieve this through their capacity to acquire a remarkable range of diverse catabolic genes and their robust cellular physiology. Rhodococcus appear to have adopted a strategy of hyperrecombination associated with a large genome. Notably, they harbour large linear plasmids that contribute to their catabolic diversity by acting as 'mass storage' for a large number of catabolic genes. In addition, there is increasing evidence that multiple pathways and gene homologues are present that further increase the catabolic versatility and efficiency of Rhodococcus.

Plasma power measurement and hysteresis in the E-H transition of a rf inductively coupled plasma system

An experimental investigation of the argon plasma behavior near the E-H transition in an inductively coupled Gaseous Electronics Conference reference cell is reported. Electron density and temperature, ion density, argon metastable density, and optical emission measurements have been made as function of input power and gas pressure. When plotted versus plasma power, applied power corrected for coil and hardware losses, no hysteresis is observed in the measured plasma parameter dependence at the E-H mode transition. This suggests that hysteresis in the E-H mode transition is due to ignoring inherent power loss, primarily in the matching system.

Phase I Study Of The Poly(ADP-Ribose) Polymerase Inhibitor, AG014699, In Combination With Temozolomide in Patients with Advanced Solid Tumors

Purpose: One mechanism of tumor resistance to cytotoxic therapy is repair of damaged DNA. Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme involved in base excision repair, one of the five major repair pathways. PARP inhibitors are emerging as a new class of agents that can potentiate chemotherapy and radiotherapy. The article reports safety, efficacy, pharmacokinetic, and pharmacodynamic results of the first-in-class trial of a PARP inhibitor, AG014699, combined with temozolomide in adults with advanced malignancy.

Experimental Design: Initially, patients with solid tumors received escalating doses of AG014699 with 100 mg/m2/d temozolomide × 5 every 28 days to establish the PARP inhibitory dose (PID). Subsequently, AG014699 dose was fixed at PID and temozolomide escalated to maximum tolerated dose or 200 mg/m2 in metastatic melanoma patients whose tumors were biopsied. AG014699 and temozolomide pharmacokinetics, PARP activity, DNA strand single-strand breaks, response, and toxicity were evaluated.

Results: Thirty-three patients were enrolled. PARP inhibition was seen at all doses; PID was 12 mg/m2 based on 74% to 97% inhibition of peripheral blood lymphocyte PARP activity. Recommended doses were 12 mg/m2 AG014699 and 200 mg/m2 temozolomide. Mean tumor PARP inhibition at 5 h was 92% (range, 46-97%). No toxicity attributable to AG014699 alone was observed. AG014699 showed linear pharmacokinetics with no interaction with temozolomide. All patients treated at PID showed increases in DNA single-strand breaks and encouraging evidence of activity was seen.

Conclusions: The combination of AG014699 and temozolomide is well tolerated, pharmacodynamic assessments showing proof of principle of the mode of action of this new class of agents.

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.

SpaciMS: spatial and temporal operando resolution of reactions within catalytic monoliths

Monolithic catalysts are widely used as structured catalysts, especially in the abatement of pollutants. Probing what happens inside these monoliths during operation is, therefore, vital for modelling and prediction of the catalyst behavior. SpaciMS is a spatially resolved capillary-inlet mass spectroscopy system allowing for the generation of spatially resolved maps of the reactions within monoliths. In this study SpaciMS results combined with 3D CFD modelling demonstrate that SpaciMS is a highly sensitive and minimally invasive technique that can provide reaction maps as well as catalytic temporal behavior. Herein we illustrate this by examining kinetic oscillations during a CO oxidation reaction over a Pt/Rh on alumina catalyst supported on a cordierite monolith. These oscillations were only observed within the monolith by SpaciMS between 30 and 90% CO conversion. Equivalent experiments performed in a plug-flow reactor using this catalyst in a crushed form over a similar range of reaction conditions did not display any oscillations demonstrating the importance of intra monolith analysis. This work demonstrates that the SpaciMS offers an accurate and comprehensive picture of structured catalysts under operation.