On the dissolution of non-metallic solid elements (sulfur, selenium, tellurium and phosphorus) in ionic liquids

Ionic liquids are shown to be good solvents for elemental sulfur, selenium, phosphorus and tellurium, and can be designed to maximise the solubility of these elements. The presence of the [S-3](center dot-) radical anion in diluted solutions of sulfur in some ionic liquids has been confirmed, and is the origin of their intense blue colour (cf. lapis lazuli).

Fast, copper-free click chemistry: a convenient solid-phase approach to oligonucleotide conjugation

Solid-phase oligonucleotide conjugation by nitrile oxide-alkyne click cycloaddition chemistry has been successfully demonstrated; the reaction, compatible with all nucleobases, requires no metal catalyst and proceeds under physiological conditions.

Rapid confirmatory method for the determination of sixteen synthetic growth promoters and bisphenol A in bovine milk using dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry

A rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-residue method for the simultaneous quantitation and identification of sixteen synthetic growth promoters and bisphenol A in bovine milk has been developed and validated. Sample preparation was straightforward, efficient and economically advantageous. Milk was extracted with acetonitrile followed by phase separation with NaCl. After centrifugation, the extract was purified by dispersive solid-phase extraction with C18 sorbent material. The compounds were analysed by reversed-phase LC-MS/MS using both positive and negative ionization and operated in multiple reaction monitoring (MRM) mode, acquiring two diagnostic product ions from each of the chosen precursor ions for unambiguous confirmation. Total chromatographic run time was less than 10 min for each sample. The method was validated at a level of 1 mu g L-1. A wide variety of deuterated internal standards were used to improve method performance. The accuracy and precision of the method were satisfactory for all analytes. The confirmative quantitative liquid chromatographic tandem mass spectrometric (LC-MS/MS) method was validated according to Commission Decision 2002/657/EC. The decision limit (CC alpha) and the detection capability (CC beta) were found to be below the chosen validation level of 1 mu g L-1 for all compounds. (C) 2010 Elsevier B.V. All rights reserved.

Hot Electrons Transverse Refluxing in Ultraintense Laser-Solid Interactions

We have analyzed the coupling of ultraintense lasers (at similar to 2 X 1019 W/cm(2)) with solid foils of limited transverse extent (similar to 10 s of mu m) by monitoring the electrons and ions emitted from the target. We observe that reducing the target surface area allows electrons at the target surface to be reflected from the target edges during or shortly after the laser pulse. This transverse refluxing can maintain a hotter, denser and more homogeneous electron sheath around the target for a longer time. Consequently, when transverse refluxing takes places within the acceleration time of associated ions, we observe increased maximum proton energies (up to threefold), increased laser-to-ion conversion efficiency (up to a factor 30), and reduced divergence which bodes well for a number of applications.

Effect of self-generated magnetic fields on fast-electron beam divergence in solid targets

The collimating effect of self-generated magnetic fields on fast-electron transport in solid aluminium targets irradiated by ultra-intense, picosecond laser pulses is investigated in this study. As the target thickness is varied in the range of 25 mu m to 1.4 mm, the maximum energies of protons accelerated from the rear surface are measured to infer changes in the fast-electron density and therefore the divergence of the fast-electron beam transported through the target. Purely ballistic spreading of the fast-electrons would result in a much faster decrease in the maximum proton energy with increasing target thickness than that measured. This implies that some degree of 'global' magnetic pinching of the fast-electrons occurs, particularly for thick (>400 mu m) targets. Numerical simulations of electron transport are in good agreement with the experimental data and show that the pinching effect of the magnetic field in thin targets is significantly reduced due to disruption of the field growth by refluxing fast-electrons.

A phase I study of the Heat Shock Protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced, solid tumours.

PURPOSE: A phase I study to define toxicity and recommend a phase II dose of the HSP90 inhibitor alvespimycin (17-DMAG; 17-dimethylaminoethylamino-17-demethoxygeldanamycin). Secondary endpoints included evaluation of pharmacokinetic profile, tumor response, and definition of a biologically effective dose (BED). PATIENTS AND METHODS: Patients with advanced solid cancers were treated with weekly, intravenous (i.v.) 17-DMAG. An accelerated titration dose escalation design was used. The maximum tolerated dose (MTD) was the highest dose at which = 1/6 patients experienced dose limiting toxicity (DLT). Dose de-escalation from the MTD was planned with mandatory, sequential tumor biopsies to determine a BED. Pharmacokinetic and pharmacodynamic assays were validated prior to patient accrual. RESULTS: Twenty-five patients received 17-DMAG (range 2.5-106 mg/m(2)). At 106 mg/m(2) of 17-DMAG 2/4 patients experienced DLT, including one treatment-related death. No DLT occurred at 80 mg/m(2). Common adverse events were gastrointestinal, liver function changes, and ocular. Area under the curve and mean peak concentration increased proportionally with 17-DMAG doses 80 mg/m(2) or less. In peripheral blood mononuclear cells significant (P

A Phase I Clinical Study of Cisplatin-Incorporated Polymeric Micelles (NC-6004) in Patients with Solid Tumors

BACKGROUND: On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study. METHODS: A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10?mg?m(-2) and was increased up to 120?mg?m(-2) according to the accelerated titration method and modified Fibonacci method. RESULTS: One dose-limiting toxicity (DLT) occurred in a patient who was given 90?mg?m(-2) of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120?mg?m(-2), which led to the conclusion that the maximum tolerated dose was 120?mg?m(-2), and the recommended dose was 90?mg?m(-2), although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration-time curve of ultrafilterable platinum at 120?mg?m(-2) NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin. CONCLUSION: The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.

Guiding of Relativistic Electron Beams in Solid Targets by Resistively Controlled Magnetic Fields

Guided transport of a relativistic electron beam in solid is achieved experimentally by exploiting the strong magnetic fields created at the interface of two metals of different electrical resistivities. This is of substantial relevance to the Fast Ignitor approach to fusion energy production [M. Tabak et al., Phys. Plasmas 12, 057305 (2005)], since it allows the electron deposition to be spatially tailored-thus adding substantial design flexibility and preventing inefficiencies due to electron beam spreading. In the experiment, optical transition radiation and thermal emission from the target rear surface provide a clear signature of the electron confinement within a high resistivity tin layer sandwiched transversely between two low resistivity aluminum slabs. The experimental data are found to agree well with numerical simulations.

Phase I study of GSK461364, a specific and competitive Polo-like Kinase 1 (PLK1) inhibitor in patients with advanced solid malignancies.

Purpose: GSK461364 is an ATP-competitive inhibitor of polo-like kinase 1 (Plk1). A phase I study of two schedules of intravenous GSK461364 was conducted. Experimental Design: GSK461364 was administered in escalating doses to patients with solid malignancies by two schedules, either on days 1, 8, and 15 of 28-day cycles (schedule A) or on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (schedule B). Assessments included pharmacokinetic and pharmacodynamic profiles, as well as marker expression studies in pretreatment tumor biopsies. Results: Forty patients received GSK461364: 23 patients in schedule A and 17 in schedule B. Dose-limiting toxicities (DLT) in schedule A at 300 mg (2 of 7 patients) and 225 mg (1 of 8 patients) cohorts included grade 4 neutropenia and/or grade 3–4 thrombocytopenia. In schedule B, DLTs of grade 4 pulmonary emboli and grade 4 neutropenia occurred at 7 or more days at 100 mg dose level. Venous thrombotic emboli (VTE) and myelosuppression were the most common grade 3–4, drug-related events. Pharmacokinetic data indicated that AUC (area under the curve) and C max (maximum concentration) were proportional across doses, with a half-life of 9 to 13 hours. Pharmacodynamic studies in circulating tumor cells revealed an increase in phosphorylated histone H3 (pHH3) following drug administration. A best response of prolonged stable disease of more than 16 weeks occurred in 6 (15%) patients, including 4 esophageal cancer patients. Those with prolonged stable disease had greater expression of Ki-67, pHH3, and Plk1 in archived tumor biopsies. Conclusions: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously in schedule A. Because of the high incidence (20%) of VTE, for further clinical evaluation, GSK461364 should involve coadministration of prophylactic anticoagulation.