Analysis of the antidiabetic drug acarbose by capillary electrophoresis

This study describes the derivatization of the pseudooligosaccharide acarbose and its main metabolite, component 2, with 7-aminonaphthalene-1,3-disulfonic acid (ANDS) in human urine. Their efficient separation was possible by means of capillary zone electrophoresis, using a capillary tube of fused-silica containing 100 mM triethylammonium phosphate buffer, pH 1.5. On column laser-induced fluorescence allowed the detection of the pseudooligosaccharides in human urine in the nanomolar range. With this method, acarbose and component 2 were quantified in human urine after application of 300 mg of acarbose.     

Accelerating Monte Carlo simulations with an NVIDIA graphics processor

Modern graphics cards, commonly used in desktop computers, have evolved beyond a simple interface between processor and display to incorporate sophisticated calculation engines that can be applied to general purpose computing. The Monte Carlo algorithm for modelling photon transport in turbid media has been implemented on an NVIDIA^® 8800gt graphics card using the CUDA toolkit. The Monte Carlo method relies on following the trajectory of millions of photons through the sample, often taking hours or days to complete. The graphics-processor implementation, processing roughly 110 million scattering events per second, was found to run more than 70 times faster than a similar, single-threaded implementation on a 2.67 GHz desktop computer.

Program summary

Program title: Phoogle-C/Phoogle-GCatalogue identifier: AEEB_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEEB_v1_0.htmlProgram obtainable from: CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.: 51 264No. of bytes in distributed program, including test data, etc.: 2 238 805Distribution format: tar.gzProgramming language: C++Computer: Designed for Intel PCs. Phoogle-G requires a NVIDIA graphics card with support for CUDA 1.1Operating system: Windows XPHas the code been vectorised or parallelized?: Phoogle-G is written for SIMD architecturesRAM: 1 GBClassification: 21.1External routines: Charles Karney Random number library. Microsoft Foundation Class library. NVIDA CUDA library [1].Nature of problem: The Monte Carlo technique is an effective algorithm for exploring the propagation of light in turbid media. However, accurate results require tracing the path of many photons within the media. The independence of photons naturally lends the Monte Carlo technique to implementation on parallel architectures. Generally, parallel computing can be expensive, but recent advances in consumer grade graphics cards have opened the possibility of high-performance desktop parallel-computing.Solution method: In this pair of programmes we have implemented the Monte Carlo algorithm described by Prahl et al. [2] for photon transport in infinite scattering media to compare the performance of two readily accessible architectures: a standard desktop PC and a consumer grade graphics card from NVIDIA.Restrictions: The graphics card implementation uses single precision floating point numbers for all calculations. Only photon transport from an isotropic point-source is supported. The graphics-card version has no user interface. The simulation parameters must be set in the source code. The desktop version has a simple user interface; however some properties can only be accessed through an ActiveX client (such as Matlab).Additional comments: The random number library used has a LGPL (http://www.gnu.org/copyleft/lesser.html) licence.Running time: Runtime can range from minutes to months depending on the number of photons simulated and the optical properties of the medium.References:

[1]

http://www.nvidia.com/object/cuda_home.html.

[2]

S. Prahl, M. Keijzer, Sl. Jacques, A. Welch, SPIE Institute Series 5 (1989) 102.

     

In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites

Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.     

Excretion kinetics of ifosfamide side-chain metabolites in children on continuous and short-term infusion

Ifosfamide (IFO) requires metabolic activation by hydroxylation of the ring system to exert cytotoxic activity. A second metabolic pathway produces the cytostatically inactive metabolites 2-dechloroethyl-ifosfamide (2-D-IFO) and 3-dechloroethyl-ifosfamide (3-D-IFO) under release of chloroacetaldehyde. This side-chain metabolism has been suggested to be involved in CNS- and renal toxicity. The total urinary excretion of ifosfamide and its metabolites was investigated during 23 cycles in 22 children at doses ranging from 400 mg/m2 to 3 g/m2. The kinetics of the excretion were compared following short-term and continuous ifosfamide infusion at a dosage of 3 g/m2. IFO and side-chain metabolites were analyzed by gas chromatography, the active metabolites by indirect determination of acrolein (ACR) and IFO mustard (IFO-M) with the NBP test. 59+/-15% of the applied dose could be recovered in the urine, 23+/-9% as unmetabolized IFO. The main metabolite was 3-D-IFO (14+/-4%) followed by isophosphoramide mustard (IFO-M) (13+/-4%) and 2-D-IFO (8+/-3%). Neither the total amount recovered nor the excretion kinetics of ifosfamide and side-chain metabolites showed obvious schedule dependency. The excretion kinetics of side-chain metabolites as well as unmetabolized IFO were nearly superimposable on short-term and continuous infusion. Even after 1-hour infusion there was a lag of 3 - 6 hours until dechloroethylation became relevant. Therefore, differences in toxicity and efficacy cannot be explained by an influence of the application time on the metabolic profile of ifosfamide.     

Object‐based land‐cover classification for the Phoenix metropolitan area: optimization vs. transportability

An object‐based approach was utilized in the development of two urban land‐cover classification schemes on high‐resolution (0.6 m), true‐colour aerial photography of the Phoenix metropolitan area, USA. An initial classification scheme was heavily weighted by standard nearest‐neighbour (SNN) functions generated by samples from each of the classes, which produced an enhanced accuracy (84%). A second classification was developed from the initial classification scheme in which SNN functions were transformed into a fuzzy‐rule set, creating a product transportable to different areas of the same imagery, or for land‐cover change detection with similar imagery. A comprehensive accuracy assessment revealed a slightly lower overall accuracy (79%) for the rule‐based classification. We conclude that the transportable classification scheme is satisfactory for general land‐cover analyses; yet classification accuracy can be enhanced at site‐specific venues with the incorporation of nearest‐neighbour functions using class samples.     

An object-based analysis filtering algorithm for airborne laser scanning

Ground filtering is a key process to derive digital terrain models from airborne laser scanning data. Although many methods have been developed to tackle the filtering problem, it has not been fully solved so far. Current algorithms mainly focus on neighbourhood-based or directional filtering approaches. A new object-based analysis (OBA) method is proposed in this article. First, a grid index algorithm accelerates access to unorganized cloud points. Then, a segmentation algorithm is deployed based on the index, and objects are obtained. A filtering logic that utilizes the objects' characteristics is designed. Following this, the performance of the method is comprehensively tested using publicly available International Society for Photogrammetry and Remote Sensing (ISPRS) test data sets for nine urban and six rural regions, and the results are compared to those of eight other algorithms. The OBA method implemented in this article reveals good results without scene-wise optimization of the parameters, and it ranks third or fourth in most of the cases.     

Electrical Coupling Between Cells and Graphene Transistors

In this work, both experimental data and a model are presented on the coupling between living cells and graphene solution‐gated field‐effect transistors. Modified HEK 293 cells are successfully cultured on graphene transistor arrays and electrically accessed by the patch clamp method. Transistor recordings are presented, showing the opening and closing of voltage‐gated potassium ion channels in the cell membrane. The experimental data is compared with the broadly used standard point‐contact model. The ion dynamics in the cell–transistor cleft are analyzed to account for the differences between the model and the experimental data revealing a significant increase in the total ionic strength in the cleft. In order to describe the influence of the ion concentration resulting from the cell activity, the ion‐sensitivity of graphene solution‐gated field‐effect transistors is investigated experimentally and modelled by considering the screening effect of the ions on the surface potential at the graphene/electrolyte interface. Finally, the model of the cell–transistor coupling is extended to include the effect of ion accumulation and ion sensitivity. The experimental data shows a very good agreement with this extended model, emphasizing the importance of considering the ion concentration in the cleft to properly understand the cell‐transistor coupling.