Patient-Derived Organoids as a Model for Cancer Drug Discovery

In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.     

Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Architected Polymer Foams via Direct Bubble Writing

Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high‐throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell–gas core droplets produced using a core–shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low‐viscosity monomer that is rapidly polymerized during the printing process. The transition between open‐ and closed‐cell foams is independently controlled by the gas used, while the foam can be tailored on‐the‐fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out‐of‐plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced.     

Multimedia summarization using social media content

In this work, we propose a novel multimedia summarization technique from Online Social Networks (OSNs). In particular, we model each Multimedia Social Network (MSN)—i.e. an OSN focusing on the management and sharing of multimedia information—using an hypergraph based approach and exploit influence analysis methodologies to determine the most important multimedia objects with respect to one or more topics of interest. Successively, we obtain from the list of candidate objects a multimedia summary using a summarization model together with an heuristics that aims to generate summaries with priority (with respect to some user keywords), continuity, variety and not receptiveness features. The performed experiments on Flickr shows the effectiveness of proposed approach.     

Microscale fluctuation assay coupled with Sep-PakR concentration as a rapid and sensitive method for screening mutagens in drinking water

A sensitive short-term mutagenicity test, the microscale fluctuation test has been coupled with a concentration method based on adsorption on Sep-Pak^R C₁₈ cartridges as a method for screening drinking water mutagens. Comparison with XAD-2 concentration method showed that Sep-Pak adsorbed 5 times higher quantity of organics but was slightly less efficient for adsorbing TOX.Microscale fluctuation test was found to be more sensitive than Ames test by testing known direct-acting mutagens and concentrates of drinking water. Samples derived from conventional treatment including chlorination from eight surface water supplies in Norway were concentrated at pH 2 by adsorption on the disposable columns. The adsorbates were tested at different doses by the microscale fluctuation assay. The mutagenic properties of drinking water samples were also related to total organic carbon (TOC), total organic halogen (TOX) and trihalomethanes (THM) concentrations. Dose-related mutagenic responses were found for all the samples with S. typhimurium TA 100 and TA98 strains without metabolic activation. Good relationship was found between mutagenicity data and TOX and THM results. The method showed to be simple, rapid and suitable for routine screening of mutagens in drinking water.     

A new approach to evaluating the toxicity and genotoxicity of disinfected drinking water

The aim of this study was to evaluate the formation of toxic and genotoxic compounds in surface drinking waters treated with two widely used disinfectants, sodium hypochlorite (NaClO) and chlorine dioxide (ClO(2)), and a new disinfectant, peracetic acid (PAA). For this purpose a pilot plant was set up to add these biocides continuously to pre-filtered lake water flowing into three different basins. During three seasonal experiments, short-term in vivo tests (with plant, fish and molluscs) and in vitro tests (with bacteria, yeast and human cells) were carried out to evaluate the formation of genotoxic disinfection by-products (DBPs). Gas chromatography/mass spectrometry (GC/MS) was used to identify DBPs produced during the different treatments, microbiological analyses were performed to test the biocidal activity of the disinfectants, and chemical analyses were carried out to evaluate the quality of the water. The pilot drinking water plant under study was useful in studying the toxicity and genotoxicity of disinfected drinking water with this combined chemical/biotoxicological approach. This paper describes the setting up of the pilot plant and sets out/reports the results of the microbiological and chemical analyses.     

Pseudopotentials and Loading Surfaces for an Endochronic Plasticity Theory with Isotropic Damage

The endochronic theory, developed in the early 70s, allows the plastic behavior of materials to be represented by introducing the notion of intrinsic time. With different viewpoints, several authors discussed the relationship between this theory and the classical theory of plasticity. Two major differences are the presence of plastic strains during unloading phases and the absence of an elastic domain. Later, the endochronic plasticity theory was modified in order to introduce the effect of damage. In the present paper, a basic endochronic model with isotropic damage is formulated starting from the postulate of strain equivalence. Unlike the previous similar analyses, in this presentation the formal tools chosen to formulate the model are those of convex analysis, often used in classical plasticity: namely pseudopotentials, indicator functions, subdifferentials, etc. As a result, the notion of loading surface for an endochronic model of plasticity with damage is investigated and an insightful comparison with classical models is made possible. A damage pseudopotential definition allowing a very general damage evolution is given.     

In situ observations of catalyst dynamics during surface-bound carbon nanotube nucleation

We present atomic-scale, video-rate environmental transmission electron microscopy and in situ time-resolved X-ray photoelectron spectroscopy of surface-bound catalytic chemical vapor deposition of single-walled carbon nanotubes and nanofibers. We observe that transition metal catalyst nanoparticles on SiOx support show crystalline lattice fringe contrast and high deformability before and during nanotube formation. A single-walled carbon nanotube nucleates by lift-off of a carbon cap. Cap stabilization and nanotube growth involve the dynamic reshaping of the catalyst nanocrystal itself. For a carbon nanofiber, the graphene layer stacking is determined by the successive elongation and contraction of the catalyst nanoparticle at its tip.     

A grid environment for high-throughput proteomics

We connect in a grid-enabled pipeline an ontology-based environment for proteomics spectra management with a machine learning platform for unbiased predictive analysis. We exploit two existing software platforms (MS-Analyzer and BioDCV), the emerging proteomics standards, and the middleware and computing resources of the EGEE Biomed VO grid infrastructure. In the setup, BioDCV is accessed by the MS-Analyzer workflow as a Web service, thus providing a complete grid environment for proteomics data analysis. Predictive classification studies on MALDI-TOF data based on this environment are presented.