Synthesis of mesoporous silica monoliths with embedded nanoparticles

Mesostructured silica-nanoparticle monolithic composites have been synthesized by dispersing prefabricated nanoparticles of gold or zeolite (silicalite) in ethanolic reaction mixtures containing SiCl4 and a Pluronic triblock copolymer template. Whereas silicalite nanoparticles were used directly, surface functionalization of the gold nanoparticles with either primed silicate ions or a discrete 3-5-nm-thick silica shell was required to increase the interfacial compatibility with the hydrophilic poly(ethylene oxide) blocks. Under these conditions, the resulting monoliths consisted of distributed nanoparticles within an ordered mesostructured silica matrix. Removal of the polymer template by calcination produced corresponding mesoporous silica-nanoparticle replicas. The combination of the structure and the porosity of the silica framework with the crystal chemical properties of the embedded nanoparticles suggests that such composites should be useful as multifunctional materials.     

Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes

A four-channel multiplexed electrospray interface on a triple quadrupole mass spectrometer was evaluated for the simultaneous validation of LC/MS/MS methods for the quantitation of loratadine and its metabolite, descarboethoxyloratadine, in four different biological matrixes. The assays were performed in rat, rabbit, mouse, and dog plasma from 1 to 1000 ng/mL using 96-well solid-phase extraction for sample preparation. The limit of quantitation of 1 ng/mL corresponded to 5.56 pg of each analyte injected on-column. For the drug, quality control samples (n = 6 at four concentrations) had precision ranging from 0.967 to 16.0% and accuracy ranging from -8.44 to 10.5% across all four species. For the metabolite, the precision ranged from 0.684 to 11.0% and the accuracy was between 6.36 and -9.06%. Intersprayer cross talk for the multiplexed electrospray ion source was evaluated as a function of analyte concentration and was less than 0.08% at concentrations as high as 1000 ng/mL. These results demonstrate the feasibility of using parallel analysis to reduce the time required for method validation and to increase sample throughput in drug development studies.     

Detection of tyrosine phosphorylated peptides by precursor ion scanning quadrupole TOF mass spectrometry in positive ion mode

Phosphorylation is a common form of protein modification. To understand its biological role, the site of phosphorylation has to be determined. Generally, only limited amounts of phosphorylated proteins are present in a cell, thus demanding highly sensitive procedures for phosphorylation site determination. Here, a novel method is introduced which enables the localization of tyrosine phosphorylation in gel-separated proteins in the femtomol range. The method utilizes the immonium ion of phosphotyrosine at m/z 216.043 for positive ion mode precursor ion scanning combined with the recently introduced Q2-pulsing function on quadrupole TOF mass spectrometers. The high resolving power of the quadrupole TOF instrument enables the selective detection of phosphotyrosine immonium ions without interference from other peptide fragments of the same nominal mass. Performing precursor ion scans in the positive ion mode facilitates sequencing, because there is a no need for polarity switching or changing pH of the spraying solvent. Similar limits of detection were obtained in this approach when compared to triple-quadrupole mass spectrometers but with significantly better selectivity, owing to the high accuracy of the fragment ion selection. Synthetic phosphopeptides could be detected at 1 fmol/microL, and 100 fmol of a tyrosine phosphorylated protein in gel was sufficient for the detection of the phosphorylated peptide in the unseparated digestion mixture and for unambiguous phosphorylation site determination. The new method can be applied to unknown protein samples, because the identification and localization of the modification is performed on the same sample.     

Surface fluctuation spectroscopy by surface-light-scattering spectroscopy

In recent years surface-light-scattering spectroscopy has been transformed from a complex optical experiment requiring substantial effort to operate effectively to a simpler instrument for which an accurate theory of operation has been developed. The accuracy and precision are sufficiently enhanced that refinement of the theory of spectral band shapes is justified to include more subtle effects such as bending moduli and thin-film forces associated with the van der Waals and the Casimir effects. We show how to develop extensions of the theory of interfacial fluctuations through the mass and the momentum balances of interfacial transport. We also show that free-energy functionals can be used to express curvature effects crisply. The results are detailed formulas that can be used to fit experimental spectra.     

Finding optimal hardware/software partitions

Most previous approaches to hardware/software partitioning considered heuristic solutions. In contrast, this paper presents an exact algorithm for the problem based on branch-and-bound. Several techniques are investigated to speed up the algorithm, including bounds based on linear programming, a custom inference engine to make the most out of the inferred information, advanced necessary conditions for partial solutions, and different heuristics to obtain high-quality initial solutions. It is demonstrated with empirical measurements that the resulting algorithm can solve highly complex partitioning problems in reasonable time. Moreover, it is about ten times faster than a previous exact algorithm based on integer linear programming. The presented methods can also be useful in other related optimization problems.     

Transition Metal Exchanged Zeolite Layers for Selectivity Enhancement of Metal-Oxide Semiconductor Gas Sensors

A novel method of improving the selectivity of metal oxide gas sensors has been developed by using catalytically active molecular sieve materials. They have been successfully introduced into a proprietary sensor array. The cracking patterns of linear alkanes over transition metal exchanged zeolite Y have been measured using a zeolite bed/GC/MS experimental set-up within a temperature range of 300degC to 400degC. Studies have been carried out regarding the effects of metal loading, zeolite type, material fabrication techniques, and operating temperature in relation to catalytic activity and selectivity. The composite sensors utilising the novel zeolite materials have been used in a custom built sensor rig that houses three dual electrode sensors and can measure real-time responses of these sensors to an introduced headspace generated from organic liquids     

An Eco‐innovation Case Study of Domestic Dishwashing through the Application of TRIZ Tools

The benefits of applying a structured method such as TRIZ (Teoriya Resheniya Izobretatelskikh Zadatch: the Russian theory of inventive problem solving) to Eco‐innovation are examined through use of two problem‐solving tools from TRIZ in an Eco‐innovation case study. A novel problem hierarchy model has been integrated to help identify the systems and sub‐systems level innovations required for Eco‐innovation. The benefits and shortcomings of the TRIZ tools, and the potential contribution of the problem hierarchy model in the innovation process are discussed.     

Posttranslational modification of Galphao1 generates Galphao3, an abundant G protein in brain

Galphao, the most abundant G protein in mammalian brain, occurs at least in two subforms, i.e., Galphao1 and Galphao2, derived by alternative splicing of the mRNA. A third Galphao1-related isoform, Galphao3, has been purified, representing about 30% of total Go in brain. Initial studies revealed distinct biochemical properties of Galphao3 as compared with other Galphao isoforms. In matrix-assisted laser desorption/ionization peptide mass mapping of gel-isolated Galphao1 and Galphao3, C-terminal peptides showed a difference of +1 Da for Galphao3. Nanoelectrospray tandem mass spectrometry sequencing revealed an Asp instead of an Asn at position 346 of Galphao3. Gel electrophoretic analysis of recombinant Galphao3 showed the same mobility as native Galphao3 but distinct to Galphao1. The conversion of 346Asn-->Asp changed the signaling properties, including the velocity of the basal guanine nucleotide-exchange reaction, which points to the involvement of the C terminus in basal guanosine 5'-[gamma-thio]triphosphate binding. No cDNA coding for Galphao3 was detected, suggesting an enzymatic deamidation of Galphao1 by a yet-unidentified activity. Therefore, Galpha heterogeneity is generated not only at the DNA or RNA levels, but also at the protein level. The relative amount of Galphao1 and Galphao3 differed from cell type to cell type, indicating an additional principle of G protein regulation.