Targeting RNA with small-molecule drugs: therapeutic promise and chemical challenges

Researchers' increasing awareness of the essential role played by RNA in many biological processes and in the progression of disease makes the discovery of new RNA targets an emerging field in drug discovery. Since most existing pharmacologically active compounds bind proteins, RNA provides nearly untapped opportunities for pharmacological development. The elucidation of the structure of the ribosome and other cellular and viral RNA motifs creates the opportunity for discovering new drug-like compounds that inhibit RNA function. However, further advances in understanding the chemistry and structure of RNA recognition are needed before these promises are fulfilled.     

Chemoenzymatic synthesis of biotinylated nucleotide sugars as substrates for glycosyltransferases

The enzymatic oxidation of uridine 5'-diphospho-alpha-D-galactose (UDP-Gal) and uridine 5'-diphospho-N-acetyl-alpha-D-galactosamine (UDP-GalNAc) with galactose oxidase was combined with a chemical biotinylation step involving biotin-epsilon-amidocaproylhydrazide in a one-pot synthesis. The novel nucleotide sugar derivatives uridine 5'-diphospho-6-biotin-epsilon-amidocaproylhydrazino-alpha-D-galactose (UDP-6-biotinyl-Gal) and uridine 5'-diphospho-6-biotin-epsilon-amidocaproylhydrazino-N-acetyl-alpha-D-galactosamine (UDP-6-biotinyl-GalNAc) were synthesized on a 100-mg scale and characterized by mass spectrometry (fast atom bombardment and matrix-assisted laser desorption/ionization time of flight) and one/two dimensional NMR spectroscopy. It could be demonstrated for the first time, by use of UDP-6-biotinyl-Gal as a donor substrate, that the human recombinant galactosyltransferases beta3Gal-T5, beta4Gal-T1, and beta4Gal-T4 mediate biotinylation of the neoglycoconjugate bovine serum albumin-p-aminophenyl N-acetyl-beta-D-glucosaminide (BSA-(GlcNAc)17) and ovalbumin. The detection of the biotin tag transferred by beta3Gal-T5 onto BSA-(GlcNAc)17 with streptavidin-enzyme conjugates gave detection limits of 150 pmol of tagged GlcNAc in a Western blot analysis and 1 pmol of tagged GlcNAc in a microtiter plate assay. The degree of Gal-biotin tag transfer onto agalactosylated hybrid N-glycans present at the single glycosylation site of ovalbumin was dependent on the Gal-T used (either beta3Gal-T5, beta4Gal-T4, or beta4Gal-T1), which indicates that the acceptor specificity may direct the transfer of the Gal-biotin tag. The potential of this biotinylated UDP-Gal as a novel donor substrate for human galactosyltransferases lies in the targeting of distinct acceptor structures, for example, under-galactosylated glycoconjugates, which are related to diseases, or in the quality control of glycosylation of recombinant and native glycoproteins.     

Chemical-Enhanced Washing for Remediation of Soils Contaminated with Marine Diesel Fuel in the Presence/Absence of Pb

The effects of the operating conditions, the initial concentrations of marine diesel fuel (MDF) and the coexisting Pb in the soil, and the ethylene diamine tetra acetic salt (EDTA) in solution on MDF removal by sodium dodecyl sulfate (SDS) washing were extensively investigated with the aim of optimizing the process parameters and determining the MDF removal efficiency by SDS under different contamination conditions. The experimental results from batch tests indicated that the majority of MDF was removed by SDS in the first 2?h, and its optimal pH was nearly neutral. Increasing the SDS concentration linearly increased the MDF removal efficiency. At a given SDS concentration, the removal efficiency was dependent on the existing forms of MDF in soils, and the free phase of MDF was found to be more easily removed than the adsorbed phase. MDF removal by SDS was significantly reduced by the coexisting Pb in soils, which likely forms a complexation with SDS and thereby enhances the partitioning of MDF in the soil by the re-adsorption of released MDF onto the hydrophobic tails of the adsorbed SDS. EDTA alone, or with SDS, could remove MDF, but the remaining MDF in the contaminated soil after EDTA washing became more difficult to be removed by SDS. Therefore, the EDTA washing followed by SDS washing is not recommended for MDF removal.     

The efficiency of sampling very high resolution images for area estimation in the European Union

Very high resolution (VHR) images are a valuable information source to estimate land cover area and land cover change. When full coverage of a region with VHR images is not affordable, a sample of images can be considered. Square grids provide a practical sampling frame for VHR images. When using a land cover map as pseudo-truth, the sampling variance is easily assessed but may be overestimated if the land cover map has a coarse resolution. To estimate the potential sampling variance of a cluster sampling scheme, we propose a method based on intra-cluster correlation (ICC) computed from a correlogram. The ‘equivalent number of points’ is a useful indicator to quantify cost-efficiency of sites of a given size. We obtained poor efficiency results for area estimation of major land cover types in the European Union (EU) with a sample of 10 km?×?10 km sites, but results are more encouraging for classes with a more scattered layout or for land cover change.     

Vocal learning in the grey parrot (Psittacus erithacus): Effects of species identity and number of trainers.

Grey parrots (Psittacus erithacus) learn referential English labels when they view and interact with 2 humans who model vocal labeling and who demonstrate referentiality and functionality of a label (I. M. Pepperberg, 1990a). To test if both trainers are necessary, the authors contrasted 2-trainer modeling with training by 1 human who presented targeted labels to a bird in concert with appropriate items, who asked questions, and who would reward attempts at the label with the item. The bird was also tutored by either 1 or 2 interactive humans in conjunction with a conspecific who already used referential labels. Referential labels were learned from multiple live tutors but not a single trainer. Presence of a conspecific enhanced learning compared with single-trainer sessions but did not affect acquisition in 2-human sessions. Specific aspects of paired tutoring seem critical for acquiring referential vocal labels. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measuring university–industry collaboration in a regional innovation system

Studies of university–industry collaboration remain subject to important limitations due to the shortage of empirical data and a lack of consistency in that obtained to date. This article puts into practice a set of universities Third Mission indicators in a regional innovation system. Selected indicators previously compiled from literature were reorganized and pre-tested. We have undertaken two face-to-face surveys of 737 firms and 765 heads of research teams, respectively. The results test the validation of indicators and provide a complex map of university–industry linkages as well as some observations on the flexibility needed to address this issue.     

A rejoinder to "Psychotherapy research ethics: Continuing the debate on controlled clinical trials."

Responds to C. A. Heflinger's (1987) critique of the present authors (1986) by reiterating their concern for the principle of autonomy. The present authors note that all patients were fully informed about the research plan and their right to withdraw. Nonetheless, the ethical criticism offered by Heflinger regarding randomization cannot be entirely dismissed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethnicity and psychopathology: A meta-analytic review of 31 years of comparative MMPI/MMPI-2 research.

Meta-analyses were performed on 25 comparative Minnesota Multiphasic Personality Inventory (MMPI) and MMPI-2 studies of 1,428 male African Americans versus 2,837 male European Americans, 12 studies of 1,053 female African Americans versus 1,470 female European Americans, and 13 studies of 500 male Latino Americans and 1,345 male European Americans. Aggregate effect sizes suggest higher scores for ethnic minority groups than for European Americans on some MMPI/MMPI-2 scales and lower scores on others. However, none of the aggregate effect sizes suggest substantive differences from either a statistical or clinical perspective. The MMPI and MMPI-2 apparently do not unfairly portray African Americans and Latinos as pathological. Effect sizes across studies generally did not vary as a function of sociodemographic variables, research setting, or use of the MMPI versus MMPI-2. It is recommended that additional between- and within-ethnic groups psychopathology research continue. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adaptative state-space model predictive control of a parabolic-trough field

Model Predictive control algorithms for trough solar plants make use of solar radiation measurements and the overall efficiency knowledge which are very useful in order to reject disturbances. However, direct solar radiation, mirror reflectivity and metal absorptance which affect overall efficiency, can only be measured locally. In this paper, an adaptative model predictive control using an unscented Kalman filter (UKF) to estimate both the effective solar radiation and the metal–fluid temperature profiles is proposed. The control algorithm is validated by tests with real data taken from the ACUREX field of the PSA in Almería (Spain).