Isoform specific gene auto-regulation via miRNAs: a case study on miR-128b and ARPP-21

In this study, we investigate whether miRNAs located within “host” protein-coding genes may regulate the expression of their host genes. We find that 43 of 174 miRNAs encoded within RefSeq genes are predicted to target their host genes. Statistical analysis of this phenomenon suggests that gene auto-regulation via miRNAs may be under positive selective pressure. Our analysis also indicates that several of the 43 miRNAs have a much lower expectation of targeting their host genes by chance than others. Among these examples, we identify miR-128b:ARPP-21 (cyclic AMP-regulated phosphoprotein, 21 kD) as a case in which both the miRNA and the target site are also evolutionarily conserved. We provide experimental support for this miRNA:target interaction via reporter silencing assays, and present evidence that this isoform-specific gene auto-regulation has been preserved in vertebrate species in order to prevent detrimental consequences of ARPP-21 over-expression in brain.     

Diffusion of linear paraffins in silicalite studied by the ZLC method in the presence of CO2

The diffusion behavior of C₄–C₁₀ n-alkanes in silicalite-1 has been investigated by using the Zero Length Column method. The diffusivities derived from measurements at different purge rates with different purge gases confirming intracrystalline diffusion control. Data are compared with results reported in the literature for MFI zeolites. The diffusivities were found to be consistent and agree well with data previous obtained by ZLC. However, these data showed a remarkable disagreement with other reported techniques (PFG-NMR, QENS and Permeation). The eventual influence of carbon dioxide (CO₂) adsorption on diffusion properties of n-alkanes in silicalite was also investigated. For this purpose, a series of experiments was performed involving hydrocarbons mixed with CO₂. Data were obtained at 303 K and flow rates between 20 and 80 mL/min. The presence of CO₂ does not seem to influence the intracrystalline transport rate of the investigated light hydrocarbons (n-C₄ and n-C₆). On the other hand, the situation for n-C₈ and n-C₁₀ is more complex. The diffusivity values are higher compared to the previously reported values.     

Computational classification of microRNAs in next-generation sequencing data

MicroRNAs (miRNAs) have been shown to play an important regulatory role in plants and animals. A large number of known and novel miRNAs can be uncovered from next-generation sequencing (NGS) experiments that measure the complement of a given cell’s small RNAs under various conditions. Here, we present an algorithm based on radial basis functions for the identification of potential miRNA precursor structures. Computationally assessing features of known human miRNA precursors, such as structural linearity, normalized minimum folding energy, and nucleotide pairing frequencies, this model robustly differentiates between miRNAs and other types of non-coding RNAs. Without relying on cross species conservation, the method also identifies non-conserved precursors and achieves high sensitivity. The presented method can be used routinely for the identification of known and novel miRNAs present in NGS experiments.     

Model-based assessment of military aircraft engine maintenance systems

The paper describes the development and use of a modular system dynamics model for analysing the dynamics and for assessing the long-term performance of military aircraft engine maintenance systems. Life-cycle engine maintenance is considered as a dynamic system whose behaviour is influenced by parameters specific to the engine's reliability and maintenance characteristics, to the operational requirements, and to the maintenance infrastructure. We show how the model can be used for supporting the aircraft procurement decision through the assessment of its engine's maintenance system, as well as for understanding and determining maintenance system behaviours, towards which operational adjustments of the maintenance infrastructure can be made in a more informed way.     

Radiative capture reactions with heavy beams: extending the capabilities of DRAGON

The European Physical Journal A - Although glueballs, as one of the type of exotic hadrons allowed by QCD, have been well established on the lattice, experimental searches up to this date for bound...     

Processing and interpretation of core-electron XPS spectra of complex plasma-treated polyethylene-based surfaces using a theoretical peak model

Interpretation of X-ray photoelectron spectroscopy (XPS) spectra of complex material surfaces, such as those obtained after surface plasma treatment of polymers, is confined by the available references. The limited understanding of the chemical surface composition may impact the ability to determine suitable coupling chemistries used for surface decoration or assess surface-related properties like biocompatibility. In this work, XPS is used to investigate the chemical composition of various ultra-high-molecular-weight polyethylene (UHMWPE) surfaces. UHMWPE doped with α-tocopherol or functionalised by active screen plasma nitriding (ASPN) was investigated as a model system. Subsequently, a more complex combined system obtained by ASPN treatment of α-tocopherol doped UHMWPE was investigated. Through ab initio orbital calculations and by employing Koopmans' theorem, the core-electron binding energies (CEBEs) were evaluated for a substantial number of possible chemical functionalities positioned on PE-based model structures. The calculated ΔCEBEs showed to be in reasonable agreement with experimental reference data. The calculated ΔCEBEs were used to develop a material-specific peak model suitable for the interpretation of merged high-resolution C 1 s, N 1 s and O 1 s XPS spectra of PE-based materials. In contrast to conventional peak fitting, the presented approach allowed the distinction of functionality positioning (i.e. centred or end-chain) and evaluation of the long-range effects of the chemical functionalities on the PE carbon backbone. Altogether, a more detailed interpretation of the modified UHMWPE surfaces was achieved whilst reducing the need for manual input and personal bias introduced by the spectral analyst.     

Characterization of the structure of calcium alumino-silicate and calcium fluoro-alumino-silicate glasses by magic angle spinning nuclear magnetic resonance (MAS-NMR)

Calcium aluminosilicate and calcium fluoro-aluminosilicate glasses have been characterized by ²⁹Si, ²⁷Al and ¹⁹F MAS-NMR. The two calcium aluminosilicate glasses examined were based on the composition 2SiO₂ · Al₂O₃ · 2CaO (ART1) and the mineral anorthite 2SiO₂ · Al₂O₃ · CaO (ART2). The observed chemical shifts for ²⁹Si and ²⁷Al agreed with previous studies. The fluorine containing glasses were based on 2SiO₂ · Al₂O₃ · (2−X)CaO · XCaF₂. The ²⁹Si chemical shift moved in a negative direction with increase fluorine content indicating a progressive reduction in the average number of non-bridging oxygens, NBO, attached to a silicon. The ²⁷Al spectra indicated the presence of four coordinate aluminium in the glasses with X=0.0-0.75, but aluminium was present in Al(IV), Al(V) and Al(VI) coordination states in the highest fluorine content glass with X=1.0. The ¹⁹F spectra indicated the presence of F-Ca(n) in low fluorine content glasses and both F-Ca(n) and Al-F-Ca(n) in high fluorine content glasses. We speculate here that the Al-F-Ca(n) species are oxyfluorides [AlO_xF_y]ⁿ⁻, where x=1-6, y=1-6 and n is the charge on the total complex when aluminium is in Al(IV), Al(V) and Al(VI) coordinate states. The reduction in the average number of NBO per silicon with increasing fluorine content is explained by fluorine converting Ca²⁺ to F-Ca(n).     

The influence of strontium substitution in fluorapatite glasses and glass-ceramics

Strontium is often substituted for calcium in order to confer radio-opacity in glasses used for dental cements, biocomposites and bioglass-ceramics. The present paper investigates the influence of substituting strontium for calcium in a glass of the following composition: 4.5SiO₂3Al₂O₃1.5P₂O₅3CaO2CaF₂, having a Ca:P ratio of 1.67 corresponding to calcium fluorapatite (Ca₅(PO₄)₃F). The glasses were characterized by magic angle spinning nuclear magnetic resonance (MAS-NMR), by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). The ²⁹Si, ²⁷Al and ³¹P NMR spectra for the glasses with different strontium contents were identical. The ¹⁹F spectra indicated the presence of F-Ca(n) and Al-F-Ca(n) species in the calcium glasses and in the strontium glasses F-Sr(n) and Al-F-Sr(n). It can be concluded that strontium substitutes for calcium with little change in the glass structure as a result of their similar charge to size ratio. The low strontium glasses bulk nucleated to a calcium apatite phase. Intermediate strontium content glasses surface nucleated to a mixed calcium-strontium apatite and the fully strontium substituted glass to strontium fluorapatite.     

Synthesis and Antiproliferative Activity of Novel Dehydroabietic Acid-Chalcone Hybrids

Dehydroabietic Acid (DHA, 1) derivatives are known for their antiproliferative properties, among others. In the context of this work, DHA was initially modified to two key intermediates bearing a C18 methyl ester, a phenol moiety at C12, and an acetyl or formyl group at C13 position. These derivatives allowed us to synthesize a series of DHA-chalcone hybrids, suitable for structure–activity relationship studies (SARS), following their condensation with a variety of aryl-aldehydes and methyl ketones. The antiproliferative evaluation of the synthesized DHA-chalcone hybrids against three breast cancer cell lines (the estrogen-dependent MCF-7 and the estrogen-independent MDA-MB-231 and Hs578T) showed that eight derivatives (33, 35, 37, 38, 39, 41, 43, 44) exhibit low micromolar activity levels (IC₅₀ 2.21–11.5 μΜ/MCF-7). For instance, some of them showed better activity compared to the commercial anticancer drug 5-FU against MCF-7 cells (33, 41, 43, 44) and against MDA-MB231 (33 and 41). Hybrid 38 is a promising lead compound for the treatment of MCF-7 breast cancer, exhibiting comparable activity to 5-FU and being 12.9 times less toxic (SI = 22.7). Thus, our findings suggest that DHA-chalcone hybrids are drug candidates worth pursuing for further development in the search for novel breast cancer therapies.     

Development and validation of a method for the determination of buprenorphine and norbuprenorphine in breast milk by gas chromatography-mass spectrometry

Buprenorphine (BUP) is used for the maintenance of opioid‐addicted pregnant women. Because BUP and its main metabolite nor‐BUP are excreted into breast milk, a sensitive and specific GC/MS method has been developed, optimized and validated for their determination in breast milk. BUP‐d4 was used as internal standard. The sample preparation includes combination of protein precipitation with solid‐phase extraction and derivatization (acetylation). The absolute recovery for both analytes was found to be higher than 87.3%. The limits of detection and quantification were 0.07 and 0.20 µg/L, respectively. The calibration curves were linear within the dynamic range 0.20–20.0 µg/L, with a correlation coefficient higher than 0.996. Intra‐ and inter‐day accuracies were ranged from ?7.06 to 4.50 and from ?5.88 to 7.00%, respectively, while intra‐ and inter‐day precision were less than 5.7 and 6.1%. The analytes were found to be stable in breast milk at 4°C for one week, at ?20°C for one month, and after three freeze–thaw cycles. The method can be used for the determination of BUP and nor‐BUP in breast milk of BUP‐maintained mothers, in order to calculate the amount of drug that could pass to the newborn via breast milk and to avoid toxic consequences of breastfeeding. Copyright © 2011 John Wiley & Sons, Ltd.