A hitchhiker's guide to G-quadruplex ligands

Over the past decade, nucleic acid chemists have seen the spectacular emergence of molecules designed to interact efficiently and selectively with a peculiar DNA structure named G-quadruplex. Initially derived from classical DNA intercalators, these G-quadruplex ligands progressively became the focal point of new excitement since they appear to inhibit selectively the growth of cancer cells thereby opening interesting perspectives towards the development of novel anti-cancer drugs. The present article aims to help researchers enter this exciting research field, and to highlight recent advances in the design of G-quadruplex ligands.     

A practical guide to nano-LC troubleshooting

Capillary LC is one of the most powerful analytical tools available for separation scientists. Its unique analytical properties are associated with numerous technical issues that may cause operation of such systems to be somehow troublesome. Because of that, a good experience in capillary LC troubleshooting is required to keep the system in shape and, in effect, to obtain reliable results. In this paper, we summarize the most important issues of the capillary systems, including void and dead volumes, leakages, sample injection, and a multidimensional LC approach. The aim of this paper was to provide practical advise on system diagnosis, and to present solutions to problems discussed. Also, several exemplary nano-LC separations are included to demonstrate some typical problems encountered in our daily work.     

A practical guide to modelling enzyme-catalysed reactions

Molecular modelling and simulation methods are increasingly at the forefront of elucidating mechanisms of enzyme-catalysed reactions, and shedding light on the determinants of specificity and efficiency of catalysis. These methods have the potential to assist in drug discovery and the design of novel protein catalysts. This Tutorial Review highlights some of the most widely used modelling methods and some successful applications. Modelling protocols commonly applied in studying enzyme-catalysed reactions are outlined here, and some practical implications are considered, with cytochrome P450 enzymes used as a specific example.     

A combined QSAR and partial order ranking approach to risk assessment

QSAR generated data appear as an attractive alternative to experimental data as foreseen in the proposed new chemicals legislation REACH. A preliminary risk assessment for the aquatic environment can be based on few factors, i.e. the octanol-water partition coefficient (Kow), the vapour pressure (VP) and the potential biodegradability of the compound in combination with the predicted no-effect concentration (PNEC) and the actual tonnage in which the substance is produced. Application of partial order ranking, allowing simultaneous inclusion of several parameters leads to a mutual prioritisation of the investigated substances, the prioritisation possibly being further analysed through the concept of linear extensions and average ranks. The ranking uses endpoint values (log Kow and log VP) derived from strictly linear 'noise-deficient' QSAR models as input parameters. Biodegradation estimates were adopted from the BioWin module of the EPI Suite. The population growth impairment of Tetrahymena pyriformis was used as a surrogate for fish lethality.     

A practical guide to the staggered herringbone mixer

An analytical model of mixing in the staggered herringbone mixer (SHM) was derived to estimate mixing parameters and provide practical expressions to guide mixer design and operation for a wide range of possible solutes and flow conditions. Mixing in microfluidic systems has historically been characterized by the mixing of a specific solute system or by the redistribution of flow streams; this approach does not give any insight into the ideal operational parameters of the mixer with an arbitrary real system. For Stokes-flow mixers, mixing can be computed from a relationship between solute diffusivity, flow rate, and mixer length. Confocal microscopy and computational fluid dynamics (CFD) modeling were used to directly determine the extent of mixing for several solutes in the staggered herringbone mixer over a range of Reynolds numbers (Re) and Péclet numbers (Pe); the results were used to develop and evaluate an analytical model of its behavior. Mixing was found to be a function of only Pe and downstream position in the mixer. Required mixer length was proportional to log(Pe); this analytical model matched well with the confocal data and CFD model for Pe<5 x 10(4), at which point the experiments reached the limit of resolution. For particular solutes, required length and mixing time depend upon Re and diffusivity. This analytical model is applicable to other solute systems, and possibly to other embodiments of the mixer, to enable optimal design, operation, and estimation of performance.     

A guide to IFCC recommendations on reference values.

Six recommendations on the theory, production, and use of reference values have been prepared by the IFCC's Expert Panel on Theory of Reference Values. This review serves as a guide to the documents and presents the main topics.     

A computer program for ranking analytical methods according to their fitness for purpose

A program for conducting automatic searches for analytical methods, selecting the most suitable ones according to quality requirements, and ranking them based on quality indices calculated from various pre-selected quality parameters is proposed. The program uses an externally updated database (Analytical Abstracts CD-ROMs or other) and customised quality schemes based on accuracy, precision, sensitivity, applicability to real samples, determination range (ratio), throughput and impact factor (from the Citation Index). It can, therefore, be used for a variety of purposes in analytical chemistry.     

Thermal analysis — A guide to the optimization of sintering processes

During the sintering of multicomponent disperse systems prepared from mixtures of the components, a variety of solid-state reactions, phase formation or dissolution, and the occurrence of a liquid phase determine the densification and the final microstructure of the material.The results are presented of investigations on the systems WC-Co and Fe-Si, through the simultaneous application of dilatometry, differential thermal analysis and thermogravimetry, coupled with metallographic and microprobe analysis.

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Zusammenfassung Beim Sintern vielkomponentiger Systeme, die aus Gemischen der Komponenten hergestellt werden, bestimmt eine Vielzahl von Festkörperreaktionen, Neubildung und Auflösung von Phasen und das Auftreten von flüssigen Phasen die Verdichtung und die erreichbare Mikrostruktur des Materials.Ergebnisse der Untersuchung in den Systemen WC-Co und Fe-Si durch kombinierten Einsatz von Dilatometrie, TG-DTA, metallographischen und Mikrosonden-Untersuchungen werden mitgeteilt.

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, , , . WC- Fe-Si , , .

     

A practical guide to microfluidic perfusion culture of adherent mammalian cells

Culturing cells at microscales allows control over microenvironmental cues, such as cell-cell and cell-matrix interactions; the potential to scale experiments; the use of small culture volumes; and the ability to integrate with microsystem technologies for on-chip experimentation. Microfluidic perfusion culture in particular allows controlled delivery and removal of soluble biochemical molecules in the extracellular microenvironment, and controlled application of mechanical forces exerted via fluid flow. There are many challenges to designing and operating a robust microfluidic perfusion culture system for routine culture of adherent mammalian cells. The current literature on microfluidic perfusion culture treats microfluidic design, device fabrication, cell culture, and micro-assays independently. Here we systematically present and discuss important design considerations in the context of the entire microfluidic perfusion culture system. These design considerations include the choice of materials, culture configurations, microfluidic network fabrication and micro-assays. We also present technical issues such as sterilization; seeding cells in both 2D and 3D configurations; and operating the system under optimized mass transport and shear stress conditions, free of air-bubbles. The integrative and systematic treatment of the microfluidic system design and fabrication, cell culture, and micro-assays provides novices with an effective starting point to build and operate a robust microfludic perfusion culture system for various applications.     

A guide to design the trajectory of active particles: From fundamentals to applications

Active particles convert external energy into motility, displaying a variety of dynamical features. Recent progress in the field has marked a shift in focus from understanding the origin and sources of active motion to controlling the dynamics and trajectory of individual microswimmers. This review explores the advancements made in a two-fold perspective—the role of particle design and that of external factors. Our main goal is to highlight the guiding principles, which determine active particle trajectory. These include, on the one hand, the role of the morphology of active particles and their assemblies in driving translation, rotation, and corresponding coupling between the two. On the other hand, the effect of environmental parameters such as the presence of physicochemical heterogeneities including interfaces, suspended obstacles, and boundaries on the modality and trajectory of active colloids. We discuss the potential of using active particles in biomedical and environmental applications through recent examples.