Phase I trial of weekly scheduling and pharmacokinetics of titanocene dichloride in patients with advanced cancer

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. PATIENTS AND METHODS: Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). RESULTS: At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (Cmax) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t1/2; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t1/2 of 0.41 hours; peak levels of UFTi were 5.2% +/- 2.5% those of TPTi. CONCLUSION: The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs.     

Targeting peptide nucleic acid-protein conjugates to structural features within duplex DNA

URF13 is the product of a mitochondrial-encoded gene (T-urf13) found only in maize plants containing the Texas male-sterile cytoplasm (cms-T), and it is thought to be responsible for both cytoplasmic male sterility and the susceptibility of cms-T maize to the fungal pathogens Bipolaris maydis race T and Phyllosticata maydis. Mitochondria isolated from cms-T maize are uniquely sensitive to pathotoxins (T-toxin) produced by these fungi and to methomyl (a commercial insecticide). URF13 acts as a receptor that specifically binds T-toxin to produce hydrophilic pores in the inner mitochondrial membrane. When expressed in Escherichia coli cells, URF13 also forms hydrophilic pores in the plasma membrane if exposed to T-toxin or methomyl. Topological studies established that URF13 contains three membrane-spanning alpha-helices, two of which are amphipathic and can contribute to pore formation. Chemical cross-linking of URF13 was used to demonstrate the existence of URF13 oligomers in cms-T mitochondria and E. coli cells. The ability of the carboxylate-specific reagent, N,N'-dicyclohexycarbodiimide, to cross-link URF13 was used in conjunction with site-directed mutagenesis to establish that the URF13 tetramer has a central core consisting of a four-alpha-helical bundle which undergoes a conformational change after interaction with T-toxin or methomyl. Overall, the experimental evidence indicates that URF13 functions as a ligand-gated, pore-forming T-toxin receptor in cms-T mitochondria.     

Controlled teleportation via photonic Faraday rotations in low-Q cavities

This paper presents feasible experimental schemes to realize controlled teleportation protocols via photonic Faraday rotations in low-Q cavities. The schemes deal with controlled teleportation of superposition states and two-particle entanglement of atomic states. The information is encoded in lambda configured three-level atoms trapped inside coupled cavities by optical fibers. Also, we estimate the success probability and the current feasibility of the schemes.     

Electrochemical determination of rusted steel surface stability

The stability of a rusted steel surface exposed to a 0.11 M sodium sulphate solution has been studied. Electrochemical impedance spectroscopy, polarization resistance and atomic absorption analysis techniques were used in conjunction with mild steel specimens rusted in a rural atmosphere and treated with different concentrations of phosphoric acid. Since most of the impedance diagrams obtained differ from the typical semicircle, it is not clear how to obtain kinetic information on the corrosion process. The polarization resistance technique gives more useful data.     

Hollow porous carbon microspheres obtained by the pyrolysis of TiO2/poly(furfuryl alcohol) composite precursors

Disordered carbon materials with high porosity were prepared through the pyrolysis of TiO₂/poly(furfuryl alcohol) composites, obtained by the sol-gel method. The composites were prepared starting from titanium tetra-isopropoxide (TTIP) and furfuryl alcohol (FA) as precursors. Two different synthetic procedures for our composites were carried out, based on the addition of furfuryl alcohol (FA) before or after the TiO₂ nanoparticles formation. Also, different TTIP/FA ratio was tested. The hybrid materials obtained by both synthetic routes were pyrolyzed, under argon flow, at 900 °C producing novel TiO₂/carbon composites. All samples were characterized by XRD, FT-IR, DR-FTIR, Raman spectroscopy and TEM. Results indicated the effective FA polymerization on TiO₂ (anatase) nanoparticles, and polymer conversion to disordered carbon after the pyrolysis, simultaneously with TiO₂ anatase-rutile phase transition. The resulting TiO₂/carbon composites were treated with HF solution aiming the oxide dissolution, yielding an extremely porous carbon material as insoluble fraction. The morphology of these porous carbon materials is strongly dependent on the synthetic route adopted for the composite precursor, varying from carbon foam to highly ordered hollow microspheres.     

An approach to reduce energy consumption and performance losses on heterogeneous servers using power capping

Journal of Scheduling - Rapid growth of demand for remote computational power, along with high energy costs and infrastructure limits, has led to treating power usage as a primary constraint in...     

Twin-image suppression in digital in-line holography based on wave-front filtering

Pattern Analysis and Applications - Digital holography is an imaging process able to recreate three-dimensional representations of objects from recording pattern interference among distinct waves....     

Ni/Al Intermetallics Plasma Transferred Arc Processing

TAILORING COMPONENT SUFACES for elevatedtemperature operations has been a goal of researchersduring the last century.Process and material selectionare the key factors for this development.In particularlythe latter can be described to have started with thedevelopment of stainless steels.Ni and Co based alloys,the superalloys,attended the increasing technologicaldemands for higher service temperatures(1).Morerecently the higher operating temperatures ofequipments,such as gas turbines,r…     

Integrating the implementation of the European Union Water Framework Directive and Floods Directive in Ireland

Water Framework Directive (WFD) statutory authorities and stakeholders in Ireland are now challenged with the issue of how the proposed programmes of measures in the newly required River Basin Management Plans - designed to protect and restore good ecology by reverting as closely as possible back to natural conditions - are to be implemented in a way that concurrently complies with other existing and emerging intersecting European Union legislation, such as the Floods Directive (FD). The WFD is driven largely by ecological considerations, whereas the FD and other legislation are more geared towards protecting physical property and mitigating public safety risks. Thus many of the same waterbodies, especially heavily modified waterbodies, arguably have somewhat competing policy objectives put upon them. This paper explores the means by which Ireland might best achieve the highest degrees of cost effectiveness, economic efficiency and institutional durability in pursuing the common and overarching objective of the WFD and FD - to ensure Irish waterways are put to their highest valued uses.