Preparation of β-Cyclodextrin-Dextran Polymers and their Use as Supramolecular Carrier Systems for Naproxen

Summary Dextran, previously activated by periodate oxidation, was grafted with mono-6-amino-6-deoxy-β-cyclodextrin, mono-6-ethylenediamino-6-deoxy-β-cyclodextrin, and mono-6-butylenediamino-6-deoxy-β-cyclodextrin by reductive alkylation in the presence of NaBH₄. The polymers were able to form inclusion complexes with Naproxen, increasing the solubility of the drug by 2.2-2.6 folds. The β-cyclodextrin-grafted dextrans were used as macromolecular carriers for Naproxen, improving the “in vivo” anti-inflammatory activity of the drug.     

Digital architecture for a piecewise-linear arbitrary-waveform generator

In this paper a digital architecture for generating piecewise-linear arbitrary waveforms is presented. The proposed design is able to generate a piecewise-linear periodic signal by only using a minimum number of input data (breakpoints). The generator circuit implements a hybrid scheme which takes advantage of two methods: the purely piecewise-linear interpolation and the lookup-table structure. From the piecewise-linear method exploits the characteristic of a reduced memory requirement as well as the capability of automatically construct a waveform by repetitive (iterative) function evaluations. From lookup-table makes use of the simplicity in hardware implementation and the higher processing speed. In order to verify the performance of this proposal, three piecewise-linear waveforms have been successfully implemented in a ATMEGA32 microcontroller. Experimental results show a fast execution speed and a reduced memory demand in the proposed circuit realization.     

Optimising the location of crossovers in conveyor-based automated material handling systems in semiconductor wafer fabs

This research presents several heuristics to optimise the location of crossovers in a conveyor-based automated material handling system (AMHS) for a semiconductor wafer fabrication facility. The objective is to determine the location of crossovers that minimises the total cost of the expected work-in-process on the conveyor and the cost of installing and operating the AMHS with the crossovers. The proposed heuristics are integrated with a queuing-based analytical model incorporating practical hardware considerations of the AMHS, such as turntables and crossovers. To illustrate the proposed heuristics’ practical application they are applied to SEMATECH's virtual wafer fabrication facility. Experimental results demonstrate that under a wide variety of operating conditions and cost scenarios the local improvement heuristic is able to identify the optimal solution and outperform other commonly used heuristics for layout design such as genetic algorithms.     

Manganese Oxide Octahedral Molecular Sieves (OMS‐2) Multiple Framework Substitutions: A New Route to OMS‐2 Particle Size and Morphology Control

Self‐assembled multidoped cryptomelane hollow microspheres with ultrafine particles in the size range of 4–6 nm, and with a very high surface area of 380 m² g^?1 have been synthesized. The particle size, morphology, and the surface area of these materials are readily controlled via multiple framework substitutions. The X‐ray diffraction and transmission electron microscopy (TEM) results indicate that the as‐synthesized multidoped OMS‐2 materials are pristine and crystalline, with no segregated metal oxide impurities. These results are corroborated by infrared (IR) and Raman spectroscopy data, which show no segregated amorphous and/or crystalline metal impurities. The field‐emission scanning electron microscopy (FESEM) studies confirm the homogeneous morphology consisting of microspheres that are hollow and constructed by the self‐assembly of pseudo‐flakes, whereas energy‐dispersive X‐ray (EDX) analyses imply that all four metal cations are incorporated into the OMS‐2 structure. On the other hand, thermogravimetric analyses (TGA) and differential scanning calorimetry (DSC) demonstrate that the as‐synthesized multidoped OMS‐2 hollow microspheres are more thermally unstable than their single‐doped and undoped counterparts. However, the in‐situ XRD studies show that the cryptomelane phase of the multidoped OMS‐2 hollow microspheres is stable up to about 450°C in air. The catalytic activity of these microspheres towards the oxidation of diphenylmethanol is excellent compared to that of undoped OMS‐2 materials.     

Calibration approach for fluorescence lifetime determination for applications using time-gated detection and finite pulse width excitation

Time-gated techniques are useful for the rapid sampling of excited-state (fluorescence) emission decays in the time domain. Gated detectors coupled with bright, economical, nanosecond-pulsed light sources like flashlamps and nitrogen lasers are an attractive combination for bioanalytical and biomedical applications. Here we present a calibration approach for lifetime determination that is noniterative and that does not assume a negligible instrument response function (i.e., a negligible excitation pulse width) as does most current rapid lifetime determination approaches. Analogous to a transducer-based sensor, signals from fluorophores of known lifetime (0.5-12 ns) serve as calibration references. A fast avalanche photodiode and a GHz-bandwidth digital oscilloscope is used to detect transient emission from reference samples excited using a nitrogen laser. We find that the normalized time-integrated emission signal is proportional to the lifetime, which can be determined with good reproducibility (typically <100 ps) even for data with poor signal-to-noise ratios ( approximately 20). Results are in good agreement with simulations. Additionally, a new time-gating scheme for fluorescence lifetime imaging applications is proposed. In conclusion, a calibration-based approach is a valuable analysis tool for the rapid determination of lifetime in applications using time-gated detection and finite pulse width excitation.     

Application of the FLIPSY pulse sequence for increased sensitivity in 1H NMR-based metabolic profiling studies

Metabolite profiling relies on optimal precision of the acquired data, which requires, among others, a high signal-to-noise ratio (S/N). In addition, increased S/N will increase the likelihood of identification of new biomarkers. Here we introduce, for the first time in metabolite profiling studies by 1H NMR, an approach to enhance the precision of multivariate regression models by use of the FLIPSY (flip angle adjustable one-dimensional NOESY) pulse sequence, augmented by a homospoil pulse after the presaturation period to provide superior baseline quality. Unlike NOESYPRESAT, the standard one-dimensional (1D) sequence generally used in metabonomic studies, FLIPSY incorporates a variable flip angle, allowing use of the Ernst angle for excitation and thus optimization of S/N ratios according to spin lattice relaxation times (T1) of individual resonances. T1 values of metabolites present in human urine were determined by inversion-recovery experiments and subsequently used in calculations of optimal experimental conditions. Comparison of human urine analysis by the FLIPSY and NOESYPRESAT demonstrated an increase of S/N ratio in the former case that amounts to approximately 7% when measured for the hippurate doublet at delta 7.84. An orthogonal projection to latent structures discriminant analysis (O-PLS-DA) model exhibited superior discrimination between controls and simulated phenylketonuria urines when using data generated by the FLIPSY as compared to NOESYPRESAT.     

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers

Understanding the molecular mechanisms governing nanoparticle–membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse‐grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di‐stearoyl‐phosphatidylcholine (DSPC) and anionic di‐stearoyl‐phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier. This can be overcome by increasing temperature, which promotes an irreversible AuNP incorporation into the lipid bilayer. NR experiments confirm the encapsulation of the AuNPs within the lipid bilayer at temperatures around 55 °C. In contrast, the AuNP adsorption is weak and impaired by heating for a DSPC–DSPG (3:1) lipid bilayer. These results demonstrate that both the lipid charge and the temperature play pivotal roles in AuNP–membrane interactions. Furthermore, NR experiments indicate that the (negative) DSPG lipids are associated with lipid extraction upon AuNP adsorption, which is confirmed by coarse‐grained MD simulations as a lipid‐crawling effect driving further AuNP aggregation. Overall, the obtained detailed molecular view of the interaction mechanisms sheds light on AuNP incorporation and membrane destabilization.     

Heteronuclear 19F-1H statistical total correlation spectroscopy as a tool in drug metabolism: study of flucloxacillin biotransformation

We present a novel application of the heteronuclear statistical total correlation spectroscopy (HET-STOCSY) approach utilizing statistical correlation between one-dimensional 19F/1H NMR spectroscopic data sets collected in parallel to study drug metabolism. Parallel one-dimensional (1D) 800 MHz 1H and 753 MHz 19F{1H} spectra (n = 21) were obtained on urine samples collected from volunteers (n = 6) at various intervals up to 24 h after oral dosing with 500 mg of flucloxacillin. A variety of statistical relationships between and within the spectroscopic datasets were explored without significant loss of the typically high 1D spectral resolution, generating 1H-1H STOCSY plots, and novel 19F-1H HET-STOCSY, 19F-19F STOCSY, and 19F-edited 1H-1H STOCSY (X-STOCSY) spectroscopic maps, with a resolution of approximately 0.8 Hz/pt for both nuclei. The efficient statistical editing provided by these methods readily allowed the collection of drug metabolic data and assisted structure elucidation. This approach is of general applicability for studying the metabolism of other fluorine-containing drugs, including important anticancer agents such as 5-fluorouracil and flutamide, and is extendable to any drug metabolism study where there is a spin-active X-nucleus (e.g., 13C, 15N, 31P) label present.     

The consistency of syntactical treatments of knowledge1 (How to compile quantificational modal logics into classical FOL)

The relative expressive power of a sentential operator □α is compared to that of a syntactical predicate L(‘α’) in the setting of first-order logics. Despite well-known results by Montague and by Thomason that claim otherwise, any of the so-called “modal” logics of knowledge and belief can be compiled into classical first-order logics that have a corresponding predicate on sentences. Moreover, through the use of a partial truth predicate, the standard modal axiom schemata can be translated into single sentences, making it possible to use conventional first-order logic theorem provers to directly derive results in a wide class of modal logics.