Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of ¹⁰B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying ¹⁰B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of ¹⁰B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.     

Determination of selected organophosphate esters in the aquatic environment of Austria

Organophosphate esters are used in multitude of applications such as flame retardants, plasticizers and lubricants. In recent years concerns have been raised in regards to the environmental impact of some of the more commonly used phosphoric acid triesters, because many of them are toxic and persistent. Liquid-liquid extraction and ultrasound-assisted solvent extraction followed by liquid chromatography coupled to tandem mass spectrometry detection (LC-MS/MS) were used for the determination of nine priority organophosphate esters in waste and surface water, as well as in sediment samples for first time in Austria. Recoveries ranged from 63% to 94% in water and from 74 to 104% in sediment with estimated quantification limits between 2.6 and 7.9 ng/l in surface water, 4.1 and 13 ng/l in effluent waste water, and between 0.48 and 11 microg/kg in sediment. The validated method was applied to determine the occurrence of the selected organophosphorus flame retardants (OPFRs) and plasticizers in the aquatic environment of Austria. The impact of the discharge of waste water treatment plants into the receiving water bodies was also studied.     

Occurrence of the <Emphasis Type="Italic">cis</Emphasis>-4,7,10, <Emphasis Type="Italic">trans</Emphasis>-13-22:4 Fatty Acid in the Family Pectinidae (Mollusca: Bivalvia)

The present study aimed to elucidate the effective phylogenetic specificity of distribution of a cis-4,7,10, trans-13-22:4 (22:4(n-9)Δ13trans) among pectinids. For this purpose, we extended the analysis of membrane glycerophospholipids FA composition to 13 species of scallops, covering 11 genera and 7 tribes representatives of the three subfamilies Chlamydinae, Palliolinae and Pectininae and the subgroup Aequipecten. In species belonging to the subfamily Pectininae and the Aequipecten subgroup, 22:4(n-9)Δ13trans was found in substantial amounts, but it was absent in other species belonging to the subfamilies Chlamydinae and Palliolinae. Homologous non-methylene-interrupted (NMI) FA, also hypothesized to differ along phylogenetic lines in bivalves, were totally absent or present only in trace amounts in representatives of the Aequipecten subgroup but ranged from 0.3 to 4.5% of the total FA in Pectinidae, Chlamydinae, and Palliolinae subfamilies. The species-specific occurrence of NMI and 22:4(n-9)Δ13trans FA in membrane lipids of pectinids agrees with the most recent phylogenies based on shell morphology and molecular characteristics. We examined the potential timing of the appearance of 22:4(n-9)Δ13trans in pectinids on a geologic time scale.     

Thermal and mechanical properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/cellulose nanowhiskers composites

Bacterial polyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was reinforced with cellulose nanowhiskers (CNW) in 1-5 wt.% concentrations using a solvent casting method. The CNW was prepared from microcrystalline cellulose (MCC) using sulfuric acid hydrolysis. The influence of CNW on the PHBV crystallization, thermal, dynamic mechanical and mechanical properties were evaluated using polarized optical microscope (POM), differential scanning calorimeter (DSC), dynamic mechanical analysis (DMA), tensile and bulge tests, respectively. POM test results demonstrated that CNW was an effective PHBV nucleation agent. Tensile strength, Young’s modulus and toughness of PHBV increased with the increasing concentration of CNW. DMA results showed an increased tan δ peak temperature and broadened transition peak, indicating restrained PHBV molecular mobility in the vicinity of the CNW surface. Storage modulus of the PHBV also increased with the addition of CNW, especially at the temperatures higher than the PHBV glass transition temperature. These results indicated that the CNW could substantially increase the mechanical properties of PHBV and this increase could be attributed to the strong interactions between these two phases.     

Factors related to birth weight: a comparison of related factors between newborns of Spanish and Colombian immigrant women in Spain

The objective of this study is to establish differentials in birth weight (BW) and related factors, in term newborns (NB) of Spanish (SP) and Colombian (CO) immigrant mothers living in Spain, between 2001-2005. Data on the NB population of SP and CO mothers was retrieved from the National Statistical Bulletin of Birth in Spain. We analysed the association with BW (Low birth weight -LBW- insufficient weight -IW- macrosomia), by the nationality of the mother; taking into account variables such as the intergenesic interval, maternal age, number of live children, maternal occupation and sex of NB. The analysis was based on frequencies and the estimation of simple and adjusted odds ratios (OR) by means of logistic regression with 95% confidence intervals (95% CI). A higher prevalence of LBW was found in SP mothers (3.4%) than in their CO counterparts (2.1%). In SP mothers a higher risk of LBW (aOR 1.89, 950% CI 1.65- 2.16) and IW (aOR 1.49, 95% CI 1.51- 1.57) was observed. In CO mothers a higher percentage of macrosomia was found (8.0%). Also, a higher percentage of LBW was observed in female new borns (SP4.1%; CO 2.7%) as well as IW (PI (SP 25.6%; CO 19.6%) (p < 0.001). Mothers aged > 40 years and having 4 or more children were associated with LBW in both nationalities. As a conclusion, NB of Colombian mothers presented a lower prevalence of LBW and IW, which could be explained by the healthy migrant effect.     

One‐Pot Palladium‐Catalyzed Synthesis of Selectively Substituted Phenanthridines by Sequential Aryl‐Aryl and Heck Couplings,Aza‐Michael and Retro‐Mannich Reactions

A catalytic synthesis of selectively substituted phenanthridines is achieved through a reaction sequence involving palladium/norbornene‐catalyzed unsymmetrical aryl‐aryl and Heck couplings followed by aza‐Michael and retro‐Mannich reactions. In spite of the many steps involved the method is very simple and allows the formation of selectively substituted phenanthridines under mild conditions in a straightforward one‐pot reaction starting from readily available aryl iodides and bromides.     

Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays

The interaction of seven novel fluorescent labeled beta-lactams with a library of six polymer materials molecularly imprinted (MI) with penicillin G (PenG) has been evaluated using both radioactive and fluorescence competitive assays. The highly fluorescent competitors (emission quantum yields of 0.4-0.95) have been molecularly engineered to contain pyrene or dansyl labels while keeping intact the 6-aminopenicillanic acid moiety for efficient recognition by the cross-linked polymers. Pyrenemethylacetamidopenicillanic acid (PAAP) is the tagged antibiotic that provides the highest selectivity when competing with PenG for the specific binding sites in a MI polymer prepared with methacrylic acid and trimethylolpropane trimethacrylate (10:15 molar ratio) in acetonitrile in the presence of PenG. Molecular modeling shows that recognition of the fluorescent analogues of PenG by the MI material is due to a combination of size and shape selectivity and demonstrates how critical the choice of label and tether chain is. PAAP has been applied to the development of a fluorescence competitive assay for PenG analysis with a dynamic range of 3-890 muM in 99:1 acetonitrile-water solution. Competitive binding studies demonstrate various degrees of cross-reactivity for some antibiotics derived from 6-aminopenicillanic acid, particularly amoxicillin, ampicillin, and penicillin V (but not oxacillin, cloxacillin, dicloxacillin, or nafcillin). Other antibiotics, such as chloramphenicol, tetracycline, or cephapirin, do not compete with PAAP for binding to the imprinted polymer. The MI assay has successfully been tested for PenG analysis in a pharmaceutical formulation.     

Distinguishing monosaccharide stereo- and structural isomers with TOF-SIMS and multivariate statistical analysis

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is utilized to examine the mass spectra and fragmentation patterns of seven isomeric monosaccharides. Multivariate statistical analysis techniques, including principal component analysis (PCA), allow discrimination of the extremely similar mass spectra of stereoisomers. Furthermore, PCA identifies those fragment peaks that vary significantly between spectra. Heavy isotope studies confirm that these peaks are indeed sugar fragments, allow identification of the fragments, and provide clues to the fragmentation pathways. Excellent reproducibility is shown by multiple experiments performed over time and on separate samples. This study demonstrates the combined selectivity and discrimination power of TOF-SIMS and PCA and suggests new applications of the technique including differentiation of subtle chemical changes in biological samples that may provide insights into cellular processes, disease progress, and disease diagnosis.     

Spark plasma sintering of self-propagating high-temperature synthesized TiC0.7/TiB2 powders and detailed characterization of dense product

In this work, the fabrication of bulk TiC_0.7/TiB₂ nanostructured composites through metastable transformation processing is investigated by taking advantages of two non-conventional powder metallurgy methods. First, the highly metastable TiC_0.7/TiB₂ agglomerated powders are synthesized by the so-called self-propagating high-temperature synthesis (SHS), followed by rapid quenching. Then, the spark plasma sintering (SPS) method is adopted to consolidate the SHSed powders.A bulk ceramic composite with nanocrystalline microstructure characterized by a high-relative density is then obtained. Dwell temperature of 1400 °C, heating time of 3 min, and total processing time equal to 5 min, while applying a mechanical pressure of 20 MPa, are found to be the optimal SPS experimental conditions in order to obtain near-fully densified samples.The obtained TiC_0.7/TiB₂ samples exhibit hardness HV5 as high as 24 GPa, modulus of elasticity of about 400 GPa, fracture toughness of about 5.6 MPa m^1/2, and a compressive strength of about 2.9 GPa. A very low-wear rate (W_v = 3.8 × 10⁻⁶ mm³/(N m)) and a good thermal shock resistance (ΔT_c = 250 °C) are also displayed. In addition, a high-abrasive wear factor (AWF) equal to 1.84 is evaluated on the basis of the achieved mechanical properties. These results make the obtained TiC_0.7/TiB₂ composite suitable for wear resistant parts as well as cutting tool materials.     

Mathematical modelling of the solubility of supercritical CO2 in poly(l-lactide) and poly(d,l-lactide-co-glycolide)

Two mathematical models, Sanchez–Lacombe equation of state and the Perturbed-Chain Statistical Associating Fluid Theory were applied for modelling the phase equilibrium for the poly(l-lactide)–CO₂ and poly(d,l-lactide-co-glycolide)–CO₂ systems. Aspen Polymer Plus software was used. The results were compared with previously obtained experimental values for solubility. The solubility of scCO₂ in the two biodegradable polymers was calculated for three different temperatures (308, 313 and 323 K) in the pressure range (10–30 MPa). The characteristic parameters for the components and the binary interaction parameters for the models were optimized in order to obtain the best fit between the estimated and the experimental gas solubility data. The results suggest that both SL EOS and PC-SAFT are reliable models in describing the phase equilibrium of the PLLA–CO₂ and PLGA–CO₂ systems at the proposed working conditions.