Lifetime and polarization of the radiative decay of excitons, biexcitons and trions in CdSe nanocrystal quantum dots

Using the pseudopotential configuration-interaction method, we calculate the intrinsic lifetime and polarization of the radiative decay of single excitons (X), positive and negative trions (X+ and X−), and biexcitons (XX) in CdSe nanocrystal quantum dots. We investigate the effects of the inclusion of increasingly more complex many-body treatments, starting from the single-particle approach and culminating with the configuration-interaction scheme. Our configuration-interaction results for the size dependence of the single-exciton radiative lifetime at room temperature are in excellent agreement with recent experimental data. We also find the following. (i) Whereas the polarization of the bright exciton emission is always perpendicular to the hexagonal c axis, the polarization of the dark exciton switches from perpendicular to parallel to the hexagonal c axis in large dots, in agreement with experiment. (ii) The ratio of the radiative lifetimes of mono- and biexcitons (X):(XX) is ~1:1 in large dots (R=19.2 Å). This ratio increases with decreasing nanocrystal size, approaching 2 in small dots (R=10.3 Å). (iii) The calculated ratio (X+):(X−) between positive and negative trion lifetimes is close to 2 for all dot sizes considered

Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis.

‘Foamy’ alveolar macrophages (FAM) observed in nonclinical toxicology studies during inhaled drug development may indicate drug-induced phospholipidosis, but can also derive from adaptive non-adverse mechanisms. Orally administered amiodarone is currently used as a model of pulmonary phospholipidosis and it was hypothesized that aerosol administration would produce phospholipidosis-induced FAM that could be characterized and used in comparative inhalation toxicology. Han-Wistar rats were given amiodarone via (1) intranasal administration (6.25 mg/kg) on two days, (2) aerosol administration (3 mg/kg) on two days, (3) aerosol administration (10 mg/kg) followed by three days of 30 mg/kg or (4) oral administration (100 mg/kg) for 7 days. Alveolar macrophages in bronchoalveolar lavage were evaluated by di_erential cell counting and high content fluorescence imaging. Histopathology and mass-spectrometry imaging (MSI) were performed on lung slices. The higher dose aerosolised amiodarone caused transient pulmonary inflammation (p < 0.05), but only oral amiodarone resulted in FAM (p < 0.001). MSI of the lungs of orally treated rats revealed a homogenous distribution of amiodarone and a putative phospholipidosis marker, di-22:6 bis-monoacylglycerol, throughout lung tissue whereas aerosol administration resulted in localization of both compounds around the airway lumen. Thus, unlike oral administration, aerosolised amiodarone failed to produce the expected FAM responses.Peer reviewedFinal Published versio

Imaging drugs, metabolites and biomarkers in rodent lung: a DESI MS strategy for the evaluation of drug-induced lipidosis

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Within drug development and pre-clinical trials, a common, significant and poorly understood event is the development of drug-induced lipidosis in tissues and cells. In this manuscript, we describe a mass spectrometry imaging strategy, involving repeated analysis of tissue sections by DESI MS, in positive and negative polarities, using MS and MS/MS modes. We present results of the detected distributions of the administered drug, drug metabolites, lipid molecules and a putative marker of lipidosis, di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP). A range of strategies have previously been reported for detection, isolation and identification of this compound, which is an isomer of di-docosahexaenoic (22:6 n-3) phosphatidylglycerol (di-22:6 PG), a commonly found lipid that acts as a surfactant in lung tissues. We show that MS imaging using MS/MS can be used to differentiate these compounds of identical mass, based upon the different distributions of abundant fragment ions. Registration of images of these fragments, and detected drugs and metabolites, is presented as a new method for studying drug-induced lipidosis in tissues. Graphical abstract.Peer reviewe

The renaissance of Odum\u27s outwelling hypothesis in \u27blue carbon\u27 science

The term ‘Blue Carbon’ was coined about a decade ago to highlight the important carbon sequestration capacity of coastal vegetated ecosystems. The term has paved the way for the development of programs and policies that preserve and restore these threatened coastal ecosystems for climate change mitigation. Blue carbon research has focused on quantifying carbon stocks and burial rates in sediments or accumulating as biomass. This focus on habitat-bound carbon led us to losing sight of the mobile blue carbon fraction. Oceans, the largest active reservoir of carbon, have become somewhat of a blind spot. Multiple recent investigations have revealed high outwelling (i.e., lateral fluxes or horizontal exports) of dissolved inorganic (DIC) and organic (DOC) carbon, as well as particulate organic carbon (POC) from blue carbon habitats. In this paper, we conceptualize outwelling in mangrove, saltmarsh, seagrass and macroalgae ecosystems, diagnose key challenges preventing robust quantification, and pave the way for future work integrating mobile carbon in the blue carbon framework. Outwelling in mangroves and saltmarshes is usually dominated by DIC (mostly as bicarbonate), while POC seems to be the major carbon species exported from seagrass meadows and macroalgae forests. Carbon outwelling science is still in its infancy, and estimates remain limited spatially and temporally. Nevertheless, the existing datasets imply that carbon outwelling followed by ocean storage is relevant and may exceed local sediment burial as a long-term ( \u3e centuries) blue carbon sequestration mechanism. If this proves correct as more data emerge, ignoring carbon outwelling may underestimate the perceived sequestration capacity of blue carbon ecosystems

The renaissance of Odum's outwelling hypothesis in 'Blue Carbon' science

The term ‘Blue Carbon’ was coined about a decade ago to highlight the important carbon sequestration capacity of coastal vegetated ecosystems. The term has paved the way for the development of programs and policies that preserve and restore these threatened coastal ecosystems for climate change mitigation. Blue carbon research has focused on quantifying carbon stocks and burial rates in sediments or accumulating as biomass. This focus on habitat-bound carbon led us to losing sight of the mobile blue carbon fraction. Oceans, the largest active reservoir of carbon, have become somewhat of a blind spot. Multiple recent investigations have revealed high outwelling (i.e., lateral fluxes or horizontal exports) of dissolved inorganic (DIC) and organic (DOC) carbon, as well as particulate organic carbon (POC) from blue carbon habitats. In this paper, we conceptualize outwelling in mangrove, saltmarsh, seagrass and macroalgae ecosystems, diagnose key challenges preventing robust quantification, and pave the way for future work integrating mobile carbon in the blue carbon framework. Outwelling in mangroves and saltmarshes is usually dominated by DIC (mostly as bicarbonate), while POC seems to be the major carbon species exported from seagrass meadows and macroalgae forests. Carbon outwelling science is still in its infancy, and estimates remain limited spatially and temporally. Nevertheless, the existing datasets imply that carbon outwelling followed by ocean storage is relevant and may exceed local sediment burial as a long-term (>centuries) blue carbon sequestration mechanism. If this proves correct as more data emerge, ignoring carbon outwelling may underestimate the perceived sequestration capacity of blue carbon ecosystems.publishedVersio

SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma

Purpose: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). Methods: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. Results: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, $p_{rec}$=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG ($p_{dom}$=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). Conclusions: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association

Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: Correlation with vascular endothelial growth factor expression

ObjectivesLymph node staging provides critical information in patients with non–small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes.MethodsForty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes.ResultsRT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months.ConclusionsRT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patient's cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases

Quantitation of endogenous metabolites in mouse tumors using mass-spectrometry imaging

Described is a quantitative-mass-spectrometryimaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysisstabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at −80 °C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment