Layer‐by‐Layer Coated Gold Nanoparticles: Size‐Dependent Delivery of DNA into Cells

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size‐dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer‐by‐layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC₅₀ value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.     

Kidney Podocytes as Specific Targets for cyclo(RGDfC)‐Modified Nanoparticles

Renal nanoparticle passage opens the door for targeting new cells like podocytes, which constitute the exterior part of the renal filter. When cyclo(RGDfC)‐modified Qdots are tested on isolated primary podocytes for selective binding to the αvβ3 integrin receptor a highly cell‐ and receptor‐specific binding can be observed. In displacement experiments with free cyclo(RGDfC) IC₅₀ values of 150 nM for αvβ3 integrin over‐expressing U87‐MG cells and 60 nM for podocytes are measured. Confocal microscopy shows a cellular Qdot uptake into vesicle‐like structures. Our ex vivo study gives clear evidence that, after renal filtration, nanoparticles can be targeted to podocyte integrin receptors in the future. This could be a highly promising approach for future therapy and diagnostics of podocyte‐associated diseases.     

Surface acoustic wave mediated carrier injection into individual quantum post nano emitters

Acousto-electric charge conveyance induced by a surface acoustic wave (SAW) is employed to dissociate photogenerated excitons. Over macroscopic distances, both electrons and holes are injected sequentially into a remotely positioned, isolated and high quality quantum emitter, a self-assembled quantum post. This process is found to be highly efficient and to exhibit improved stability at high acoustic powers when compared to direct optical pumping at the position of the quantum post. These characteristics are attributed to the wide matrix quantum well in which charge conveyance occurs and to the larger number of carriers available for injection in the remote configuration, respectively. The emission of such pumped quantum posts is dominated by recombination of neutral excitons and fully directional when the propagation direction of the SAW and the position of the quantum post are reversed.     

Thermal simulation of pulsed direct laser interference patterning of metallic substrates using the smoothed particle hydrodynamics approach

This work presents a new approach to the thermal modelling of direct laser interference patterning (DLIP). The spatial and temporal evolution of the temperature distribution within metallic substrates, which are irradiated by nanosecond pulses during the DLIP process, is computed by means of a smoothed particle hydrodynamics (SPH) method. The developed model considers the conversion of laser energy into heat within a very thin surface layer, heat conduction into the bulk material and the effect of latent heat during involved phase transformations. The importance of proper determination of characteristic SPH parameters and adequate spatial resolution of the computational domain on the accuracy of the numerical solution is discussed in detail. The computed temperature distributions are in good agreement with the results of a previously developed FEM model and correspond very well to simultaneously performed experimental investigations.     

Material Behaviour: Embedding Physical Properties in Computational Design Processes

Material behaviour computes form. In the physical world, material form is always inseparably connected to internal constraints and external forces; in the virtual space of digital design, though, form and force are usually treated as separate entities – divided into processes of geometric form generation and subsequent engineering simulation. Using the example of the interdisciplinary ICD/ITKE Research Pavilion, constructed at the University of Stuttgart in 2010, Moritz Fleischmann, Jan Knippers, Julian Lienhard, Achim Menges and Simon Schleicher explain how feedback between computational design, advanced simulation and robotic fabrication expands the design space towards previously unexplored architectural possibilities. Copyright © 2012 John Wiley & Sons, Ltd.     

A meta-analysis of work–family conflict and various outcomes with a special emphasis on cross-domain versus matching-domain relations.

A literature review of studies analyzing work–family conflict and its consequences was conducted, and 427 effect sizes were analyzed meta-analytically. Work–family conflict was analyzed bidirectionally in terms of work interference with family (WIF) and family interference with work (FIW). We assessed 3 categories of potential outcomes: work-related outcomes, family-related outcomes, and domain-unspecific outcomes. Results show that WIF and FIW are consistently related to all 3 types of outcomes. Both types of interrole conflict showed stronger relationships to same-domain outcomes than to cross-domain outcomes. Thus, WIF was more strongly associated with work-related than with family-related outcomes, and FIW was more strongly associated with family-related than with work-related outcomes. In moderator analyses, parenthood could not explain variability in effect sizes. However, time spent at work did moderate the relationships between WIF and family-related outcomes, as well as FIW and domain-unspecific outcomes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Initial steps of the metal-catalysed degradation of L-dehydroascorbic acid in acidic aqueous solutions

The initial steps of the degradation of L-de- hydroascorbic acid (L-DHA) in acidic aqueous solutions and the catalytic effect of different transition metal ions on this reaction were studied. The main product was identified as 3,6-furanosido-2,3-hexodiulosonic acid-2-hydrate (compound I) by GLC-MS and ¹³C-NMR, formed by lactone hydrolysis and hydration of the carbonyl group in the C-2 position of L-dehydroascorbic acid. In addition, number of other compounds were detected; they are formed from compound I by simple enolisation, lactonisation, hydration and dehydration reactions as well as by cleavage and formation of cyclic half acetal bonds. The chemical structures of these compounds were tentatively deduced by the mass spectra of their TMS derivatives and a reaction scheme for their formation is proposed. The velocity and the direction of the reactions were found to be strongly influenced by the presence of catalytic amounts of different transition metal ions. It was concluded that in acidic medium, in contrast to the situation in neutral and alkaline solutions, the opening of the lactone ring of L-DHA is, to a certain degree, a reversible reaction.     

A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors

In this study, we synthesized and evaluated a new spirocyclic piperidine derivative 3 , containing a 4‐fluorobutyl side chain, as a PET radioligand for neuroimaging of σ₁ receptors. In vitro, compound 3 displayed high affinity for σ₁ receptors (K_i=1.2 nM ) as well as high selectivity. [¹⁸F] 3 radiosynthesis was performed from the corresponding tosylate precursor, with high radiochemical yield (45–51 %), purity (>98 %), and specific activity (>201 GBq μmol^?1). Metabolic stability of [¹⁸F] 3 in the brain of CD‐1 mice was verified, and no penetration of peripheral radiometabolites into the cerebral tissue was observed. Results of ex vivo autoradiography revealed that the distribution of [¹⁸F] 3 in the brain corresponded to regions with high σ₁ receptor density. The highest region‐specific total‐to‐nonspecific ratio was determined in the facial nucleus (4.00). Biodistribution studies indicated rapid and high levels in brain uptake of [¹⁸F] 3 (2.2 % ID per gram at 5 min p.i.). Pre‐administration of haloperidol significantly inhibited [¹⁸F] 3 uptake into the brain and σ₁ receptor‐expressing organs, further confirming in vivo target specificity.