Thermoresponsive polymer micropatterns fabricated by dip-pen nanolithography for a highly controllable substrate with potential cellular applications

We report a novel approach for patterning thermoresponsive hydrogels based on N,N-diethylacrylamide (DEAAm) and bifunctional Jeffamine ED-600 by dip-pen nanolithography (DPN). The direct writing of micron-sized thermoresponsive polymer spots was achieved with efficient control over feature size. A Jeffamine-based ink prepared through the combination of organic polymers, such as DEAAm, in an inorganic silica network was used to print thermosensitive arrays on a thiol-silanised silicon oxide substrate. The use of a Jeffamine hydrogel, acting as a carrier matrix, allowed a reduction in the evaporation of ink molecules with high volatility, such as DEAAm, and facilitated the transfer of ink from tip to substrate. The thermoresponsive behaviour of polymer arrays which swell/de-swell in aqueous solution in response to a change in temperature was successfully characterised by atomic force microscopy (AFM) and Raman spectroscopy: a thermally-induced change in height and hydration state was observed, respectively. Finally, we demonstrate that cells can adhere to and interact with these dynamic features and exhibit a change in behaviour when cultured on the substrates above and below the transition temperature of the Jeffamine/DEAAm thermoresponsive hydrogels. This demonstrates the potential of these micropatterned hydrogels to act as a controllable surface for cell growth

TOF studies for dedicated PET with open geometries

[EN] Recently, two novel PET devices have been developed with open geometries, namely: breast and prostate-dedicated scanners. The breast-dedicated system comprises two detector rings of twelve modules with a field of view of 170 mm x 170 mm x 94 mm. Each module consists of a continuous trapezoidal LYSO crystal and a PSPMT. The system has the capability to vary the opening of the rings up to 60 mm in order to allow the insertion of a needle to perform a biopsy procedure. The prostate system has an open geometry consisting on two parallel plates separated 28 cm. One panel includes 18 detectors organized in a 6 x 3 matrix while the second one comprises 6 detectors organized in a 3 x 2 matrix. All detectors are formed by continuous LYSO crystals of 50 mm x 50 mm x15 mm, and a SiPM array of 12 x 12 individual photo-detectors. The system geometry is asymmetric maximizing the sensitivity of the system at the prostate location, located at about 2/3 in the abdomen-anus distance. The reconstructed images for PET scanners with open geometries present severe artifacts due to this peculiarity. These artifacts can be minimized using Time Of Flight information (TOF). In this work we present a TOF resolution study for open geometries. With this aim, the dedicated breast and prostate systems have been simulated using GATE (8.1 version) with different TOF resolutions in order to determine the image quality improvements that can be achieved with the existing TOF-dedicated electronics currently present in the market. The images have been reconstructed using the LMOS algorithm including TOF modeling in the calculation of the voxel-Line Of Response emission probabilities.This work was supported in part by the Spanish Government Grants TEC2016-79884-C2 and RTC-2016-5186-1 and by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant Agreement No. 695536).Moliner, L.; Ilisie, V.; González Martínez, AJ.; Oliver-Gil, S.; Gonzalez, A.; Giménez-Alventosa, V.; Cañizares, G.... (2019). TOF studies for dedicated PET with open geometries. Journal of Instrumentation. 14:1-8. https://doi.org/10.1088/1748-0221/14/02/C02006S181

Random walks on randomly evolving graphs

A random walk is a basic stochastic process on graphs and a key primitive in the design of distributed algorithms. One of the most important features of random walks is that, under mild conditions, they converge to a stationary distribution in time that is at most polynomial in the size of the graph. This fundamental property, however, only holds if the graph does not change over time; on the other hand, many distributed networks are inherently dynamic, and their topology is subjected to potentially drastic changes. In this work we study the mixing (i.e., convergence) properties of random walks on graphs subjected to random changes over time. Specifically, we consider the edge-Markovian random graph model: for each edge slot, there is a two-state Markov chain with transition probabilities p (add a non-existing edge) and q (remove an existing edge). We derive several positive and negative results that depend on both the density of the graph and the speed by which the graph changes

Direct observation of templated two-step nucleation mechanism during olanzapine hydrate formation

Investigating crystal nucleation at the nanoscale is of significant interest, in particular as more complex, non-classical routes have roused questions about the classical view of homo- and hetero-nucleation processes. Here, we report the direct observation of a two-step nucleation mechanism during the transformation of anhydrous olanzapine to olanzapine dihydrate. Atomic force microscopy studies of the dominant (100)OZPNI face of olanzapine form I single crystals in contact with water show the formation and growth of dense nanodroplets concentrated around ledge sites. In unstirred solution, apparent ordering and crystallisation from these droplets occurs with olanzapine dihydrate D produced by the templating effect of the underlying olanzapine I lattice. In contrast, under stirred conditions a kinetic dihydrate polymorph, dihydrate B, nucleates probably due to the detachment of nanodroplets from the surface during stirring and a consequent loss of template effect. Computational modelling of the binding of olanzapine growth units on crystal ledges reveals many strongly bound dimer positions unrelated to either crystal structure. This impedes surface integration and contributes to the growth of disordered clusters at the ledge site. Nanocrystal modelling shows that the (100)OZPNI surface favours the nucleation of dihydrate D over the kinetic form. This work gives an important insight into heterogeneous two step nucleation where the first step, the formation of a prenucleation droplet, can in the second step, bifurcate, either to produce the stable form by templating, or the kinetic form on detachment of the nanodroplets

Entanglement Entropy from a Holographic Viewpoint

The entanglement entropy has been historically studied by many authors in order to obtain quantum mechanical interpretations of the gravitational entropy. The discovery of AdS/CFT correspondence leads to the idea of holographic entanglement entropy, which is a clear solution to this important problem in gravity. In this article, we would like to give a quick survey of recent progresses on the holographic entanglement entropy. We focus on its gravitational aspects, so that it is comprehensible to those who are familiar with general relativity and basics of quantum field theory.Comment: Latex, 30 pages, invited review for Classical and Quantum Gravity, minor correction

Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ~280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics

Microfluidic manufacturing of phospholipid nanoparticles: Stability, encapsulation efficacy, and drug release

Liposomes have been the centre of attention in research due to their potential to act as drug delivery systems. Although its versatility and manufacturing processes are still not scalable and reproducible. In this study, the microfluidic method for liposomes preparation is presented. DMPC and DSPC liposomes containing two different lipid/cholesterol ratios (1:1 and 2:1) are prepared. Results from this preparation process were compared with the film hydration method in order to understand benefits and drawbacks of microfluidics. Liposomes characterisation was evaluated through stability studies, encapsulation efficacy and drug release profiles of hydrophilic and lipophilic compounds. Stability tests were performed during 3 weeks and the liposomes properties of the most stable formulations were determined using Infrared Microscopy and Atomic Force Microscopy. Microfluidic allows loading of drugs and assembly in a quick single step and the chosen flow ratio for liposomes formulation plays a fundamental role for particle sizes. One hydrophilic and one lipophilic compounds were incorporated showing how formulation and physic-chemical characteristics can influence the drug release profile