The absolute stereochemistry and cytotoxicity of the ascidian-derived metabolite, longithorone J

The absolute stereochemistry of longithorone J (1) from the ascidian Aplidium longithorax has been determined using the advanced Mosher method. Based on biosynthetic reasoning and chiroptical data comparison the absolute stereochemistry for longithorone K (2) was also assigned. Longithorone J was tested for cytotoxicity against the cell lines SHSY5Y, HEK293T and A549. Compound 1 showed minimal cytotoxicity towards the SHSY5Y and HEK293T cell lines.     

Integration of digital signal processing technologies with pulsed electron paramagnetic resonance imaging

The integration of modern data acquisition and digital signal processing (DSP) technologies with Fourier transform electron paramagnetic resonance (FT-EPR) imaging at radiofrequencies (RF) is described. The FT-EPR system operates at a Larmor frequency (L(f)) of 300MHz to facilitate in vivo studies. This relatively low frequency L(f), in conjunction with our approximately 10MHz signal bandwidth, enables the use of direct free induction decay time-locked subsampling (TLSS). This particular technique provides advantages by eliminating the traditional analog intermediate frequency downconversion stage along with the corresponding noise sources. TLSS also results in manageable sample rates that facilitate the design of DSP-based data acquisition and image processing platforms. More specifically, we utilize a high-speed field programmable gate array (FPGA) and a DSP processor to perform advanced real-time signal and image processing. The migration to a DSP-based configuration offers the benefits of improved EPR system performance, as well as increased adaptability to various EPR system configurations (i.e., software configurable systems instead of hardware reconfigurations). The required modifications to the FT-EPR system design are described, with focus on the addition of DSP technologies including the application-specific hardware, software, and firmware developed for the FPGA and DSP processor. The first results of using real-time DSP technologies in conjunction with direct detection bandpass sampling to implement EPR imaging at RF frequencies are presented.     

Investigation of Bi-2223 high temperature superconducting tape as the material for gradient coil in MRI

The use of Bi-2223 high temperature superconducting (HTS) tape as a material for gradient coils in MRI is evaluated in this paper. Bi-2223 tapes have a very high critical current and a very low power loss. A HTS tape gradient coil is expected to provide much higher gradient strength and generate much lower heating than a copper coil. Measurements of the AC power loss of Bi-2223 tapes at typical operating frequencies for gradient coils are presented. The degradation of the critical current and its effect on the increase of AC power loss is analyzed. Practical technical issues such as resistance, gradient strength and mechanical performance are also discussed. A prototype Bi-2223 HTS tape gradient coil is evaluated to verify the concept.     

SVMtm: support vector machines to predict transmembrane segments

A new method has been developed for prediction of transmembrane helices using support vector machines. Different coding schemes of protein sequences were explored, and their performances were assessed by crossvalidation tests. The best performance method can predict the transmembrane helices with sensitivity of 93.4% and precision of 92.0%. For each predicted transmembrane segment, a score is given to show the strength of transmembrane signal and the prediction reliability. In particular, this method can distinguish transmembrane proteins from soluble proteins with an accuracy of approximately 99%. This method can be used to complement current transmembrane helix prediction methods and can be used for consensus analysis of entire proteomes. The predictor is located at http://genet.imb.uq.edu.au/predictors/SVMtm.     

In recognition of the sixtieth birthday of James K. Knowles

Dedication

In recognition of the sixtieth birthday of James K. Knowles     

Comparison of second derivative-spectrophotometric and reversed-phase HPLC methods for the determination of prednisolone in pharmaceutical formulations.

Second derivative-spectrophotometric and high-performance liquid chromatographic methods for the determination of prednisolone in pharmaceutical formulations have been developed. Determination of prednisolone in tablets was conducted by using a second-order derivative UV spectrophotometric method at 250 nm (n = 5). Standards for the calibration graph ranging from 5.0 to 35.0 microg/ml were prepared from stock solution. The proposed method was accurate, with 98% recovery value, and precise, with a coefficient of variation (CV) of 1.38. These results were compared with those obtained by an exclusively developed isocratic reversed-phase high-performance liquid chromatography (HPLC) method. An isocratic reversed-phase Bondapak C(18) column with acetonitrile-citrophosphate buffer (pH 5; 45:55 v/v) mobile phase was used and UV detector was set to 241 nm using 11 alpha-hydroxyprogesterone as an internal standard. Calibration solutions used in HPLC were in the range from 2 to 300 microg/ml. Results obtained by derivative UV spectrophotometric method were comparable to those obtained by HPLC method, as far as analysis of variance (ANOVA) test, F(calculated), 0.762 and F(theoretical), 3.89, results were concerned.     

On the homogenization of a diffusion–deformation problem in strongly heterogeneous media

We consider a porous fluid-saturated medium with periodic distribution of heterogeneities where the value of permeability decreases with the scale parameters. Homogenization of such double-porous material is performed using the method of periodic unfolding. The resulting homogenized macroscopic model is featured by the fading memory effect in the viscoelastic behaviour. This paper is based upon the work sponsored by the Ministry of Education of the Czech Republic under the research project MSM 49777513 03.     

A microwave-assisted stereoselective synthesis of polyandrocarpamines A and B

A stereoselective synthesis of the marine natural products, polyandrocarpamines A and B, has been achieved using a high-yielding one-step aldol condensation reaction under microwave conditions. The structures of both synthetic compounds were confirmed following 1D and 2D NMR, UV, IR and MS spectral analysis, and by comparison with literature data. Both synthetic natural products were assigned Z geometry about their exocyclic double bond on the basis of ¹³C/¹H long-range coupling constants, which were measured using a gHSQMBC experiment. Polyandrocarpamines A and B were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system). Polyandrocarpamine A displayed selective cytotoxicity towards the SF268 cell line with a GI₅₀ value of 65 μM.     

On some three-field mixed systems

In this work we present a modified mixed formulation for some three-field problems. Under a special hypothesis the modified formulation is such that: the verification of two (BB) conditions is avoided and one has to deal only with one, and the new problem has exactly the same solution as the old one. This revised version was published online in June 2006 with corrections to the Cover Date.     

Cathepsin K Inhibitors for Treatment of Osteoporosis

Cysteine Proteases have been implicated in a broad spectrum of disease processes including cancer, arthritis, and viral and parasitie diseases^[1]. Cathepsin K, a cysteine protease of the papain superfamily, is selectively expressed in osteoclasts and has been implicated in the process of bone resouption^[2]. It is therefore considered a promising therapeutic target for treating diseases charccterized by excessive bone loss, such as osteoporosis^[3]. Several chemotypes of cathepsin K inhibitors will be reviewed. The design and synthesis of potent inhibitors will also be discussed.