In situ phase behaviour of a high capacity LiCoPO4 electrode during constant or pulsed charge of a lithium cell

The phase changes that occur during lithium extraction from LiCoPO4 in lithium half-cells were studied using synchrotron X-ray diffraction. The existence of two two-phase regions with an intermediate phase present was observed. Significant variations in the composition of the phases of nominal stoichiometry LiCoPO4, Li2/3CoPO4 and CoPO4 resulted in unit cell volume variations. On current pulsing, lattice parameter shifts and phase recovery were directly observed

Solvothermal water-diethylene glycol synthesis of LiCoPO4 and effects of surface treatments on lithium battery performance

Olivine-structured LiCoPO4 is prepared via a facile solvothermal synthesis, using various ratios of water/ diethylene glycol co-solvent, followed by thermal treatment under Ar, air, 5%H2/N2 or NH3. The diethylene glycol plays an important role in tailoring the particle size of LiCoPO4. It is found that using a ratio of water/diethylene glycol of 1 : 6 (v/v), LiCoPO4 is obtained with a homogenous particle size of �150 nm. The bare LiCoPO4 prepared after heating in Ar exhibits high initial discharge capacity of 147 mA h g1 at 0.1C with capacity retention of 70% after 40 cycles. This is attributed to the enhanced electronic conductivity of LiCoPO4 due to the presence of Co2P after firing under Ar. The effects of carbon, TiN and RuO2 coating are also examined. Contrary to other studies, it is found that the solvothermally synthesised LiCoPO4 samples produced here do not require conductive coatings to achieve good performance

Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies

Purpose: Response to standard oncologic treatment is limited in colorectal cancer. The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing; however, drug discovery is currently limited by the lack of translation of CMS to preclinical models. Experimental Design: We analyzed CMS in primary colorectal cancers, cell lines, and patient-derived xenografts (PDX). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell-intrinsic gene expression signals, and performed high-throughput in vitro drug screening (n = 459 drugs) to analyze subtype-specific drug sensitivities. Results: The distinct molecular and clinicopathologic characteristics of each CMS group were validated in a single-hospital series of 409 primary colorectal cancers. The new, cancer cell-adapted classifier was found to perform well in primary tumors, and applied to a panel of 148 cell lines and 32 PDXs, these colorectal cancer models were shown to recapitulate the biology of the CMS groups. Drug screening of 33 cell lines demonstrated subtype-dependent response profiles, confirming strong response to EGFR and HER2 inhibitors in the CMS2 epithelial/canonical group, and revealing strong sensitivity to HSP90 inhibitors in cells with the CMS1 microsatellite instability/immune and CMS4 mesenchymal phenotypes. This association was validated in vitro in additional CMS-predicted cell lines. Combination treatment with 5-fluorouracil and luminespib showed potential to alleviate chemoresistance in a CMS4 PDX model, an effect not seen in a chemosensitive CMS2 PDX model. Conclusions: We provide translation of CMS classification to preclinical models and uncover a potential for targeted treatment repurposing in the chemoresistant CMS4 group. (C) 2017 AACR.Peer reviewe

Direct observation of active material concentration gradients and crystallinity breakdown in LiFePO4 electrodes during charge/discharge cycling of lithium batteries

The phase changes that occur during discharge of an electrode comprised of LiFePO4, carbon, and PTFE binder have been studied in lithium half cells by using X-ray diffraction measurements in reflection geometry. Differences in the state of charge between the front and the back of LiFePO4 electrodes have been visualized. By modifying the X-ray incident angle the depth of penetration of the X-ray beam into the electrode was altered, allowing for the examination of any concentration gradients that were present within the electrode. At high rates of discharge the electrode side facing the current collector underwent limited lithium insertion while the electrode as a whole underwent greater than 50% of discharge. This behavior is consistent with depletion at high rate of the lithium content of the electrolyte contained in the electrode pores. Increases in the diffraction peak widths indicated a breakdown of crystallinity within the active material during cycling even during the relatively short duration of these experiments, which can also be linked to cycling at high rate

Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity

Peer reviewe

Establishment of patient-derived tumor organoids to functionally inform treatment decisions in metastatic colorectal cancer

Colorectal cancer; Personalized medicine; ResistanceCáncer colorrectal; Medicina personalizada; ResistenciaCàncer colorectal; Medicina personalitzada; ResistènciaBackground Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor resistance to therapy, due to their high capacity to resemble tumor characteristics. Materials and methods We used viable tumor tissue from two cohorts of patients with mCRC, naïve or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping. Results A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOX–bevacizumab and mitomycin–capecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumab–second mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy. Conclusions Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.This Translational Research Fellowship Project was supported by the ESMO with the aid of a grant from Amgen, by the Accelerator (ACRCelerator) [grant number A26825] and Ayuda a médicos jóvenes investigadores from Fundacion Científica—Asociacion Española Contra el Cancer (FC-AECC)/Associazione Italiana per la Ricerca sul Cancro (AIRC)/Cancer Research United Kingdom (CRUK) and by Familia Armangué. Any views, opinions, findings, conclusions or recommendations expressed in this material are those solely of the author(s) and do not necessarily reflect those of ESMO or Amgen. We thank Regione Campania (I-Cure Research Project) [grant number: Cup 21C17000030007], ESMO Translational Research Fellowship Program

IVUS-based imaging modalities for tissue characterization: similarities and differences

Gray-scale intravascular ultrasound (IVUS) is the modality that has been established as the golden standard for in vivo imaging of the vessel wall of the coronary arteries. The use of IVUS in clinical practice is an important diagnostic tool used for quantitative assessment of coronary artery disease. This has made IVUS the de-facto invasive imaging method to evaluate new interventional therapies such as new stent designs and for atherosclerosis progression-regression studies. However, the gray-scale representation of the coronary vessel wall and plaque morphology in combination with the limited resolution of the current IVUS catheters makes it difficult, if not impossible, to identify qualitatively (e.g. visually) the plaque morphology similar as that of histopathology, the golden standard to characterize and quantify coronary plaque tissue components. Meanwhile, this limitation has been partially overcome by new innovative IVUS-based post-processing methods such as: virtual histology IVUS (VH-IVUS, Volcano Therapeutics, Rancho Cordova, CA, USA), iMAP-IVUS (Bostoc Scientific, Santa Clara, CA, USA), Integrated Backscatter IVUS (IB-IVUS) and Automated Differential Echogenicity (ADE)

Recovery and resilience of tropical forests after disturbance

The time taken for forested tropical ecosystems to re-establish post-disturbance is of widespread interest. Yet to date there has been no comparative study across tropical biomes to determine rates of forest re-growth, and how they vary through space and time. Here we present results from a meta-analysis of palaeoecological records that use fossil pollen as a proxy for vegetation change over the past 20,000 years. A total of 283 forest disturbance and recovery events, reported in 71 studies, are identified across four tropical regions. Results indicate that forests in Central America and Africa generally recover faster from past disturbances than those in South America and Asia, as do forests exposed to natural large infrequent disturbances compared with post-climatic and human impacts. Results also demonstrate that increasing frequency of disturbance events at a site through time elevates recovery rates, indicating a degree of resilience in forests exposed to recurrent past disturbance

A Meta-Analysis of Effects of Bt Crops on Honey Bees (Hymenoptera: Apidae)

L.) are the most important pollinators of many agricultural crops worldwide and are a key test species used in the tiered safety assessment of genetically engineered insect-resistant crops. There is concern that widespread planting of these transgenic crops could harm honey bee populations.We conducted a meta-analysis of 25 studies that independently assessed potential effects of Bt Cry proteins on honey bee survival (or mortality). Our results show that Bt Cry proteins used in genetically modified crops commercialized for control of lepidopteran and coleopteran pests do not negatively affect the survival of either honey bee larvae or adults in laboratory settings.Although the additional stresses that honey bees face in the field could, in principle, modify their susceptibility to Cry proteins or lead to indirect effects, our findings support safety assessments that have not detected any direct negative effects of Bt crops for this vital insect pollinator