On-Column Preconcentration of Anti-Inflammatory Drugs in River Water by Anion-Selective Exhaustive Injection-Sweeping-MEKC

A high-sensitivity on-column preconcentration method, anion selective exhaustive injection (ASEI)-sweeping in micellar electrokinetic capillary chromatography (MEKC) has been developed for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs): diclofenac sodium, ibuprofen, fenoprofen, naproxen, and ketoprofen in water samples. To achieve the best results of the ASEI-sweeping-MEKC method, conditions which affected preconcentration were examined, including the sodium dodecyl sulfate concentration, composition of the sample matrix, composition and injection length of the water plug, the concentration and the injection length of the high-conductivity buffer, and finally the sample injection time. Under the optimum stacking conditions the method was validated for the determination of the studied NSAIDs in river water samples with limits of detection ranging between 29 and 58 ng mL^?1, and without any previous sample pretreatment.     

Identification of ligands for the Tau exon 10 splicing regulatory element RNA by using dynamic combinatorial chemistry

We describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). A series of ligands that combine the small aminoglycoside neamine and heteroaromatic moieties (azaquinolone and two acridines) have been identified by using DCC. These compounds effectively bind the stem-loop RNA target (the concentration required for 50% RNA response (EC(50)): 2-58 μM), as determined by fluorescence titration experiments. Importantly, most of them are able to stabilize both the wild-type and the +3 and +14 mutated sequences associated with the development of FTDP-17 without producing a significant change in the overall structure of the RNA (as analyzed by circular dichroism (CD) spectroscopy), which is a key factor for recognition by the splicing regulatory machinery. A good correlation has been found between the affinity of the ligands for the target and their ability to stabilize the RNA secondary structure.     

Cationic polyfluorenes for intracellular delivery of proteins

Two cationic polyfluorene derivatives, quaternary amine 1 and guanidine 2 sheathed systems, were prepared as potential carriers to mediate import of proteins into cells without requiring covalent attachment to the protein. Neither polymer showed significant cytotoxicities (IC(50) 100 μM) when exposed to Clone 9 rat liver cells. Both polymers were shown to mediate import of a series of four proteins chosen because they have different pI values, sizes, and variable organic fluor attachments. Once inside the cells, the quaternary amine system 1 released more of its cargo into regions outside the lysosomes. In one exploratory experiment, pyrenebutyrate was shown to accelerate import of a protein system by polymer 1.     

Role of hydrogen in dimerizaton of aluminum clusters: a theoretical study

We have used density functional theory to investigate how Al(13) cluster dimers can be formed with or without a bridging hydrogen. We have identified several stable dimers in which 0, 1, or 2 hydrogen atoms link two bare clusters together. Each of these structures can adsorb further H atoms in atop sites on the surface of the dimer. Additional dimers were identified with 3 and 4 H atoms linking the clusters but these are only stable in the multihydrogenated form. Reaction profiles for the formation of these dimers from a range of cluster and H atom combinations indicate that the dimer structures are energetically favored over the isolated clusters. This observation may have significant implications for the design of cluster-assembled materials.     

Tailoring Spectral and Photochemical Properties of Bioinspired Retinal Mimics by in Silico Engineering

Controlling the spectral tunability and isomerization activity is currently one of the hot topics in the design of photoreversible molecular switches for application in optoelectronic devices. The present work demonstrates how to manipulate the absorption of the retinal protonated Schiff base (rPSB) chromophore over the entire visible range by targeted functionalization of the retinal backbone. Moreover, a correlation between the vertical excitation energy and the profile of the potential energy surface of the bright excited state responsible for the photoreactivity of rPSB is established. This correlation was exploited to rank the functionalized rPSBs into different classes with characteristic photoisomerization activity. Eventually, the synergic effects of functionalization and of external electric fields in the range of a few MV cm⁻¹ were applied to achieve reversable and regioselective control of the photoisomerization propensity of selected rPBS derivatives.     

Electrochemical Magnetic Immunosensors for the Determination of Ceruloplasmin

Electrochemical immunosensors for ceruloplasmin (Cp) are reported for the first time. Two configurations involving magnetic beads (MBs) functionalized with Protein A or Streptavidin for immobilization of Cp antibodies were compared, using competitive immunoassay with synthesized alkaline phosphatase‐Cp conjugate. Upon capturing MBs‐immunoconjugates onto screen‐printed carbon electrodes, quantification of Cp was accomplished by DPV measurement of 1‐naphthol generated after 1‐naphthylphosphate addition. Linear ranges of calibration curves and detection limits were 0.1–1000 µg/mL and 0.040 µg/mL (Protein A‐MBs), and 0.025–20 µg/mL and 0.018 µg/mL (Strept‐MBs). Good results were obtained in the determination of Cp in spiked human serum samples.     

Screening for illicit and medicinal drugs in whole blood using fully automated SPE and ultra‐high‐performance liquid chromatography with TOF‐MS with data‐independent acquisition

A broad forensic screening method for 256 analytes in whole blood based on a fully automated SPE robotic extraction and ultra‐high‐performance liquid chromatography (UHPLC) with TOF‐MS with data‐independent acquisition has been developed. The limit of identification was evaluated for all 256 compounds and 95 of these compounds were validated with regard to matrix effects, extraction recovery, and process efficiency. The limit of identification ranged from 0.001 to 0.1 mg/kg, and the process efficiency exceeded 50% for 73 of the 95 analytes. As an example of application, 1335 forensic traffic cases were analyzed with the presented screening method. Of these, 992 cases (74%) were positive for one or more traffic‐relevant drugs above the Danish legal limits. Commonly abused drugs such as amphetamine, cocaine, and frequent types of benzodiazepines were the major findings. Nineteen less frequently encountered drugs were detected e.g. buprenorphine, butylone, cathine, fentanyl, lysergic acid diethylamide, m‐chlorophenylpiperazine, 3,4‐methylenedioxypyrovalerone, mephedrone, 4‐methylamphetamine, p‐fluoroamphetamine, and p‐methoxy‐N‐methylamphetamine. In conclusion, using UHPLC–TOF‐MS screening with data‐independent acquisition resulted in the detection of common drugs of abuse as well as new designer drugs and more rarely occurring drugs. Thus, TOF‐MS screening of blood samples constitutes a practical way for screening traffic cases, with the exception of δ‐9‐tetrahydrocannabinol, which should be handled in a separate method.     

Evolution of harmonic maps on manifolds flat at infinity

The aim of this article is to prove a global existence result with small data for the heat flow for harmonic maps from a manifold flat at infinity into a compact manifold. By flat at infinity we mean that the growth rate of the volumes of the balls on the manifold is the same as in the flat space. This is true for any manifold for small enough radius, but is in general not true when the radius of the ball grows. So prescribing such a growth rate also at infinity selects a class of manifolds on which our result holds. In this setting estimates are available for the heat kernel and its gradient on the base manifold. From such estimates it is easy to get L ^p −L ^q bounds for the heat kernel. A contraction principle argument then yields a local existence result in a suitable Sobolev space and a global existence result for small data.     

First year mathematics undergraduates’ settled images of tangent line

This study concerns 182 first year mathematics undergraduates’ perspectives on the tangent line of function graph in the light of a previous study on Year 12 pupils’ perspectives. The aim was the investigation of tangency images that settle after undergraduates’ distancing from the notion for a few months and after their participation in university admission examination. To this end we related the performances of the undergraduates and the pupils in the same questions of a questionnaire; we classified the undergraduates in distinct groups through Latent Class Analysis; and, we examined this classification according to the Analytical Local, Geometrical Global and Intermediate Local perspectives on tangency we had identified among pupils. The findings suggest that more undergraduates than pupils demonstrated intermediate perspectives on tangency. Also, the undergraduates’ settled images were influenced by persistent images about tangency and their prior experience in the context of preparation for and participation in the examination.