Liquid hyperpolarized 129Xe produced by phase exchange in a convection cell

Journal ArticleWe present a method for the production of liquid hyperpolarized 129Xe that employs spin-exchange optical pumping in the gas phase and subsequent phase exchange with a column of xenon liquid. A convection loop inside the sealed glass cell allows efficient transfer of magnetization between the gas and liquid phases. By condensing to liquid a large fraction of the sample, this scheme permits the polarization of many more 129Xe atoms in a given sealed-cell volume than would otherwise be possible. We have thus far produced a steady-state polarization of 8% in 0.1 mL of liquid with a characteristic rise time of <15 min

Role of water states on water uptake and proton transport in Nafion using molecular simulations and bimodal network

Using molecular simulations and a bimodal domain network, the role of water state on Nafion water uptake and water and proton transport is investigated. Although the smaller domains provide moderate transport pathways, their effectiveness remains low due to strong, resistive water molecules/domain surface interactions. The water occupancy of the larger domains yields bulk-like water, and causes the observed transition in the water uptake and significant increases in transport properties

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

High content screening of patient-derived cell lines highlights the potential of non-standard chemotherapeutic agents for the treatment of glioblastoma

<div><p>Background</p><p>Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation.</p><p>Methods</p><p>Seven cancer stem cell lines were derived from patients with GBM and, along with the established cell line U87-MG, each patient-derived line was cultured in tandem in serum-free conditions as adherent monolayers and three-dimensional neurospheres. Chemotherapeutics were screened at multiple concentrations and cells double-stained to observe their effect on both cell death and proliferation. Sensitivity was classified using high-throughput algorithmic image analysis.</p><p>Results</p><p>Cell line specific drug responses were observed across the seven patient-derived cell lines. Few agents were seen to have radio-sensitizing effects, yet some drug classes showed a marked difference in efficacy between monolayers and neurospheres. <i>In vivo</i> validation of six drugs suggested that cell death readout in a three-dimensional culture scenario is a more physiologically relevant screening model and could be used effectively to assess the chemosensitivity of patient-derived GBM lines.</p><p>Conclusion</p><p>The study puts forward a number of non-standard chemotherapeutics that could be useful in the treatment of recurrent GBM, namely mitoxantrone, bortezomib and actinomycin D, whilst demonstrating the potential of HCS to be used for personalized treatment based on the chemosensitivity profile of patient tumor cells.</p></div

Bland-Altman method comparison of assay models demonstrated no overall bias for potency, whilst highlighting specific drugs to take forward for validation.

<p>All pEC50s were stacked by patient-derived line. Mean difference and lower and upper limits of agreements (95% CI) are indicated by dotted lines. Values outside these limits can be considered real biological differences.</p

pEC50 values highlighted general resistance of GBM cell lines and cell line specific responses to chemotherapeutics and irradiation.

<p>Heat Map was populated using best-fit pEC50 values generated from dose-response curves, then color mapped categorically according to the legend. Each heat map color and corresponding number (1,2,3 etc.), corresponds to a log change in concentration of drug (100,000 μM, 10,000 μM, 1000 μM etc.). Red values of a pEC50 of 9 or above would indicate an EC50 of 1nm or below, indicating high efficacy, whereas any values categorized green-blue or below would likely be poor drug candidates as they correspond to EC50 values above 10μM. Any data Prism was unable to fit was colored black—this was typically due to an inability to generate an EC50 with that drug candidate because of inefficiency at high concentrations.</p

Patient demographics, clinical features and cell line designations.

<p>Patient demographics, clinical features and cell line designations.</p

Cell line characterization demonstrated stem-cell characteristics and tumorigenicity <i>in vivo</i>.

<p>(A-B) U87 neurosphere culture demonstrating Nestin (green) and Sox2 (red) staining in serum-free culture (s.b. = 100μm). (C) U87 orthotopic implantation model showing large well-defined masses within the brain parenchyma, showing staining for anti-human nuclear antigen (green) (s.b. = 1000μm). (D) High power field (x40) of well-demarcated tumour edge showing anti-human nuclear antigen staining of tumour cells (s.b. = 50μm). (E-F) TS18 in serum free neurosphere culture showing uniform Nestin and Sox2 staining (s.b. = 100μm). (G) Orthotopic implantation of TS18-GFP cells with combined GFP (green) and anti-human nuclear antigen (red) staining to show diffuse infiltration of cells both within the parenchyma and across the corpus callosum into the opposite hemisphere (s.b. = 1000μm). (H) High power field (x20) showing area of diffuse infiltration and co-expression of GFP and anti-human nuclear antigen in implanted cells (s.b. = 100μm). (I-J) GS1 neurosphere culture showing uniform Nestin and Sox2 staining in serum free culture. (K) Orthotopic implantation of GS1 cells into the striatum with anti-vimentin staining. Vimentin staining is characteristic of gliosarcoma and is not found in the parenchyma, and was used to trace GS1 cells within the parenchyma (s.b. = 1000μm). (L) High power field (x20) showing diffusely infiltrating vimentin positive cells (green) within the corpus callosum (s.b. = 100μm).</p