Polydopamine as an adhesive coating for open tubular capillary electrochromatography

Polydopamine (PolyD) coating was used as an adhesive layer in the preparation of biological stationary phases for open tubular capillary electrochromatography (OT-CEC). The influence of coating solution freshness, coating time, temperature and dopamine hydrochloride concentration on the PolyD layer formation was studied. The performance of the polyD coating was monitored by measuring the electro-osmotic flow in coated capillaries. Following polyD coating of the capillary, secondary layer material (e.g. cell membrane solutions, phospholipid mixtures or mitochondria) was inserted into the capillary for at least 1?h. The performance of these double-coated capillaries (a polyD layer+a biological material layer) was compared with capillaries containing the respective biological material directly attached to the capillary wall. The study reveals that the presence of polyD layer in fused silica capillaries improves the performance of lipid and membrane fragment coatings in capillaries. At the same time, the thickness of the polyD layer does not have marked impact on the secondary coatings. Analysis with test analytes demonstrated that double-coated capillaries can be applied to study membrane-drug interactions.     

Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide

Recently a new non-coded amino acid was designed as a replacement for Arg, to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This constrained Arg analog, denoted c(5)Arg, was engineered to also promote the stability of the CREKA bioactive conformation. The conformational profile of the CREKA analog obtained by replacing Arg by c(5)Arg has been extensively investigated in this work. Two molecular dynamics simulations-based strategies have been employed: a modified simulated annealing and replica exchange. Results obtained using both techniques show that the conformational features of the new analog fulfill the purpose of its design. The new CREKA analog not only preserves the main structural attributes found for the bioactive conformation of the parent peptide but also shows lower flexibility. Moreover, the conformational profile of the mutated peptide narrows towards the most stable structures previously observed for the parent CREKA peptide.     

A practical synthesis of Rho-Kinase inhibitor Y-27632 and fluoro derivatives and their evaluation in human pluripotent stem cells

A practical synthesis of the Rho-Kinase inhibitor Y-27632 and two new fluoro derivatives was achieved in seven steps and with a good overall yield of 45% starting from commercially available (R)-1-phenylethylamine. Compared to Y-27632 the new fluoro derivatives showed reduced or no effect on hPSC vitality and expansion after dissociation in human pluripotent stem cells.     

Novel ligands for a purine riboswitch discovered by RNA-ligand docking

The increasing number of RNA crystal structures enables a structure-based approach to the discovery of new RNA-binding ligands. To develop the poorly explored area of RNA-ligand docking, we have conducted a virtual screening exercise for a purine riboswitch to probe the strengths and weaknesses of RNA-ligand docking. Using a standard protein-ligand docking program with only minor modifications, four new ligands with binding affinities in the micromolar range were identified, including two compounds based on molecular scaffolds not resembling known ligands. RNA-ligand docking performed comparably to protein-ligand docking indicating that this approach is a promising option to explore the wealth of RNA structures for structure-based ligand design.     

Determination of selenium status using the nail biologic monitor in a canine model

Toenails and fingernails are routinely used to estimate selenium status in epidemiological studies; however, literature validating nail selenium concentration as a surrogate for critical organs is limited. In this study diets of intact male dogs were selenium supplemented at two physiological levels (3 and 6 μg/kg/day) in two different forms, selenomethionine and selenium-enriched bioformed yeast. The selenium-adequate basal diet consumed by the treatment and control groups during the 4-week run-in period and throughout the trial contained 0.3 ppm selenium. After 7 months the dogs in the two treatment groups and the control group were euthanized. Representative tissue samples from prostate, brain, liver, heart and skeletal muscle were collected, rinsed and frozen. Toenail clippings from multiple toes were also collected. Selenium was determined by neutron activation analysis using Se77m (half life = 17.4 s) at the University of Missouri Research Reactor Center. NIST SRM 1577, Bovine Liver was analyzed as a quality control. The analysts were blinded to control and treatment group assignments. As expected, tissue selenium levels increased proportionally with supplementation. A slightly greater increase in tissue selenium was observed for the purified selenomethionine compared to the bioformed yeast; however this trend was significant only for brain tissue. Toenail selenium concentrations and tissue selenium were highly correlated (p < 0.003) with Pearson coefficients of 0.759 (skeletal muscle), 0.745 (heart), 0.729 (brain), 0.723 (prostate), and 0.632 (liver). The toenail biologic monitor accurately assesses selenium status in skeletal muscle, heart, brain, prostate, and liver in the canine model.     

Multinuclear NMR Characterization of Cyanuric Fluoride (2,4,6‐Trifluoro‐1,3,5‐triazine)

Although 2,4,6‐trifluoro‐1,3,5‐triazine, C₃F₃N₃, is a highly symmetrical molecule, its NMR parameters can be obtained by reducing its symmetry through the introduction of ¹⁴N/¹⁵N and ¹²C/¹³C isotopomers. Experimental and computed chemical shifts of cyanuric fluoride have been obtained for ¹³C, ¹⁵N, and ¹⁹F. Spin‐spin coupling constants have been measured and compared with previous experimental data and with the complete set of computed EOM‐CCSD coupling constants.     

GloMIQO: Global mixed-integer quadratic optimizer

This paper introduces the global mixed-integer quadratic optimizer, GloMIQO, a numerical solver addressing mixed-integer quadratically-constrained quadratic programs to ${\varepsilon}$ -global optimality. The algorithmic components are presented for: reformulating user input, detecting special structure including convexity and edge-concavity, generating tight convex relaxations, partitioning the search space, bounding the variables, and finding good feasible solutions. To demonstrate the capacity of GloMIQO, we extensively tested its performance on a test suite of 399 problems of diverse size and structure. The test cases are taken from process networks applications, computational geometry problems, GLOBALLib, MINLPLib, and the Bonmin test set. We compare the performance of GloMIQO with respect to four state-of-the-art global optimization solvers: BARON 10.1.2, Couenne 0.4, LindoGLOBAL 6.1.1.588, and SCIP 2.1.0.     

Spatial release from masking in children with normal hearing and with bilateral cochlear implants: effect of interferer asymmetry

Spatial release from masking (SRM) was measured in groups of children with bilateral cochlear implants (BiCIs, average ages 6.0 and 7.9 yr) and with normal hearing (NH, average ages 5.0 and 7.8 yr). Speech reception thresholds (SRTs) were measured for target speech in front (0°), and interferers in front, distributed asymmetrically toward the right (+90°/+90°) or distributed symmetrically toward the right and left (+90°/-90°). In the asymmetrical condition both monaural "better ear" and binaural cues are available. In the symmetrical condition, listeners rely heavily on binaural cues to segregate sources. SRM was computed as the difference between SRTs in the front condition and SRTs in either the asymmetrical or symmetrical conditions. Results showed that asymmetrical SRM was smaller in BiCI users than NH children. Furthermore, NH children showed symmetrical SRM, suggesting they are able to use binaural cues for source segregation, whereas children with BiCIs had minimal or absent symmetrical SRM. These findings suggest that children who receive BiCIs can segregate speech from noise under conditions that maximize monaural better ear cues. Limitations in the CI devices likely play an important role in limiting SRM. Thus, improvement in spatial hearing abilities in children with BiCIs may require binaural processing strategies.