HPLC methods that use chromatographic retention times for gaining information about the properties of compounds for the purpose of designing drug molecules are reviewed. Properties, such as lipophilicity, protein binding, phospholipid binding, and acid/base character can be incorporated in the design of molecules with the right biological distribution and pharmacokinetic profile to become an effective drug. Standardization of various methodologies is suggested in order to obtain data suitable for inter-laboratory comparison. The published HPLC methods for lipophilicity, acid/base character, protein and phospholipid binding are critically reviewed and compared with each other using the solvation equation approach. One of the most important discussion points is how these data can be used in models and how they can influence the drug discovery process. Therefore, the published models for volume of distribution, unbound volume of distribution and drug efficiency are also discussed. The general relationships between the chemical structure and biomimetic HPLC properties are described in view of ranking and selecting putative drug molecules.
Contributors:E. Remetean, B. Dolives, F. Souvannavong, T. Germa, JB. Ginestet, A. Torres, T. Mousset
The ROLIS, CIVA-P and OSIRIS instruments on-board the Philae lander and the Rosetta orbiter acquired high-resolution images during the lander׳s descent towards the targeted landing site Agilkia, during its unexpected rebounds and at the final landing site Abydos on comet 67P/Churyumov–Gerasimenko. We, exploited these images, using robotic vision techniques, to locate the first touchdown on the surface of the comet nucleus, to reconstruct the lander׳s 3D trajectory during the descent and at the beginning of the first rebound, and to create local digital terrain models and depth maps of Agilkia and Abydos sites. Using the ROLIS close-up images we could also determine the actual movements of the lander between the beginning and the end of the First Science Sequence and we propose a new lander׳s bubble movement command meant to increase the probability for a successful drilling during a hypothetical future Long Term Science phase.
Contributors:José l. Beltrán, joseph j. Pignatello, Marc Teixidó
Geochemists and soil chemists commonly use parametrized sorption data to assess transport and impact of pollutants in the environment. However, this evaluation is often hampered by a lack of detailed sorption data analysis, which implies further non-accurate transport modeling. To this end, we present a novel software tool to precisely analyze and interpret sorption isotherm data. Our developed tool, coded in Visual Basic for Applications (VBA), operates embedded within the Microsoft ExcelTM environment. It consists of a user-defined function named ISOT_Calc, followed by a supplementary optimization Excel macro (Ref_GN_LM). The ISOT_Calc function estimates the solute equilibrium concentration in the aqueous and solid phases (Ce and q, respectively). Hence, it represents a very flexible way in the optimization of the sorption isotherm parameters, as it can be carried out over the residuals of q, Ce, or both simultaneously (i.e. orthogonal distance regression). The developed function includes the most usual sorption isotherm models, as predefined equations, as well as the possibility to easily introduce custom-defined ones. Regarding the Ref_GN_LM macro, it allows the parameter optimization by using a Levenberg-Marquardt modified Gauss-Newton iterative procedure. In order to evaluate the performance of the presented tool, both function and optimization macro have been applied to different sorption data examples described in the literature. Results showed that the optimization of the isotherm parameters was successfully achieved in all cases, indicating the robustness and reliability of the developed tool. Thus, the presented software tool, available to researchers and students for free, has proven to be a user-friendly and an interesting alternative to conventional fitting tools used in sorption data analysis.
Contributors:Andreas Schoob, Dennis Kundrat, Stefan Lekon, Lüder A. Kahrs, Tobias Ortmaier
This paper presents a real-time method for interactive focus positioning in laser microsurgery. Registration of stereo vision and a surgical laser is performed in order to combine surgical scene and laser workspace information. In particular, stereo image data is processed to three-dimensionally reconstruct observed tissue surface as well as to compute and to highlight its intersection with the laser focal range. Regarding the surgical live view, three augmented reality concepts are presented providing visual feedback during manual focus positioning. A user study is performed and results are discussed with respect to accuracy and task completion time. Especially when using color-encoded distance superimposed to the live view, target positioning with sub-millimeter accuracy can be achieved in a few seconds. Finally, transfer to an intraoperative scenario with endoscopic human in vivo and cadaver images is discussed demonstrating the applicability of the image overlay in laser microsurgery.
The hydrodynamics of a three-phase micro-packed bed reactor and its effect on catalysed benzyl alcohol oxidation with pure oxygen were studied in a silicon–glass microstructured reactor. The microreactor was operated at 120°C and 1barg and contained a channel with a 300μm×600μm cross-section, packed with 1wt% Au–Pd/TiO2 catalyst, 65μm in average diameter. Improvements in the conversion of benzyl alcohol and selectivity to benzaldehyde were observed with increasing gas-to-liquid ratio, which coincided with a change in the flow pattern from a liquid-dominated slug to a gas-continuous flow regime. The observed enhancement is attributed to improved external mass transfer, associated with an increase in the gas–liquid interfacial area and reduction in the liquid film thickness that occur with gradual changes in the flow pattern. A maximum selectivity of 93% to benzaldehyde was obtained under partial wetting – which introduced the added benefit of direct gas–solid mass transfer – outperforming the selectivity in a conventional glass stirred reactor. However, this was at the expense of a reduction in the conversion. A response surface model was developed and then used to predict optimal operating conditions for maximum benzaldehyde yield, which were in the gas-continuous flow regime. This corresponded to relatively high gas flow rate in conjunction with moderate liquid flow rate, ensuring sufficient catalyst wetting with a thin film to reduce transport resistances.
The transcription factor Pitx3 null mutant (Pitx3Null) mice have a constitutive perinatal-onset and symmetric bilateral dopamine (DA) loss in the striatum. In these mice l-3,4-dihydroxyphenylalanine (l-dopa) induces apparently normal horizontal movements (walking) but also upward movements consisting of the vertical body trunk and waving paws that are absent in normal animals and in animals with the classic unilateral 6-hydroxydopamine (6-OHDA) lesion-induced DA denervation. Thus, a concern is that the perinatal timing of the DA loss and potential developmental abnormalities in Pitx3Null mice may underlie these upward movements, thus reducing the usefulness as a DA denervation model. Here we show that in normal wild-type (Pitx3WT) mice with adult-onset symmetric, bilateral 6-OHDA-induced DA lesion in the dorsal striatum, l-dopa induces normal horizontal movements and upward movements that are qualitatively identical to those in Pitx3Null mice. Furthermore, after unilateral 6-OHDA lesion of the residual DA innervation in the striatum in Pitx3Null mice, l-dopa induces contraversive rotation that is similar to that in Pitx3WT mice with the classic unilateral 6-OHDA lesion. These results indicate that in Pitx3Null mice, the bilateral symmetric DA denervation in the dorsal striatum is sufficient for expressing the l-dopa-induced motor phenotype and the perinatal timing of their DA loss is not a determining factor, providing further evidence that Pitx3Null mice are a convenient and suitable mouse model to study the consequences of DA loss and dopaminergic replacement therapy in Parkinson’s disease.
Contributors:José Antonio Mora-Lorca, Beatriz Sáenz-Narciso, Christopher J. Gaffney, Francisco José Naranjo-Galindo, José Rafael Pedrajas, David Guerrero-Gómez, Agnieszka Dobrzynska, Peter Askjaer, Nathaniel J. Szewczyk, Juan Cabello, Antonio Miranda-Vizuete
Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress and have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 worms is prevented by restoring GSR-1 activity in the cytoplasm but not in mitochondria. Given the fact that the thioredoxin redox systems are dispensable in C. elegans, our data support a prominent role of the glutathione reductase/glutathione pathway in maintaining redox homeostasis in the nematode.
Contributors:Johannes Kamp, Ronny Hänsch, Gregor Kendzierski, Matthias Kraume, Olaf Hellwich
The fundamental analysis of drop coalescence probability in liquid/liquid systems is necessary to reliably predict drop size distributions in technical applications. For this crucial investigation two colliding oil drops in continuous water phase were recorded with different high speed camera set-ups under varying conditions. In order to analyze the huge amount of recorded image sequences with varying resolutions and qualities, a robust automated image analysis was developed. This analysis is able to determine the trajectories of two colliding drops as well as the important events of drop detachment from cannulas and their collision. With this information the drop velocity in each sequence is calculated and mean values of multiple drop collisions are determined for serial examinations of single drop collisions. Using the developed automated image analysis for drop trajectory and velocity calculation, approximately 1–2 recorded high speed image sequences can be evaluated per minute.
Contributors:Zhi-Yin Wang, Tian-Lei Zhang, Qiu-Hui Li, Qi Xue, Rui Wang
The oxidation of CO over Au3− cluster was investigated using the DFT by selecting peroxo-like adsorbate intermediate, Au3CO(O2)−, of CO and O2 over the Au3− cluster, as the reactant model. Based on the transition state investigation at UB3LYP/LANL2DZ, the energies at the UB3LYP/aug-cc-pVTZ-PP//LANL2DZ level theory and corresponding relativistic effective core potential (RECP) for Au, 6-311+G∗ for carbon and oxygen atoms, the reaction potential energy diagrams and pathways were analyzed. For the selecting Au3CO(O2)− as the initial intermediated proceeded through a typical LH mechanism and forming a complex of CO2 and Au3O−, and the subsequent intermediate, Au3OCO−, formed by the reaction of CO with Au3O− were also analyzed. The results indicated that the CO oxidation followed the LH or ER mechanism, and their rate constants increased with increasing temperature. For the main reason of CO oxidation over Au3− cluster with no perceptible catalytic activity, it should be the no sufficient peroxo-like complex (Au3COO2−, 1A) formation due to the very low content of low-spin O2 under normal conditions, and that the peroxo-like compound also showed a low oxidation rate at low temperature.
Rolling is a frequently used high-efficiency motion pattern for articulated loop robots. An important issue is planning the angle of each joint to keep a loop closed on the fly and to roll forward stably. Most of the current approaches achieve a gait table by designing a few key postures or a numerical approximation of a special loop geometry (e.g., an ellipse), which is difficult to implement for non-experts and makes motion planning time-consuming. The change in joint angles for many current loop gaits is not smooth. The serpenoid curve, whose curvature changes sinusoidally, exhibits the advantage of making angle changes smooth. Based on this feature, a generalized Serpenoid Polygon model for loop gait is proposed, which extends Hirose's Serpenoid Oval to Polygon. Furthermore, we derive its scalable planning model for loop robots with different numbers of joints, which is easy to implement. The influence of key parameters on the performance of this model is investigated through numerous dynamics simulations with a general linkage-mechanism. In addition, loop forming and rolling-pattern switching are studied to facilitate the implementation of this model. In the end, the applications of the model are discussed, its effectiveness is validated through experiments using the UBot modular robot.