LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues

© 2018 Elsevier GmbH A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 μm x 5 μm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 μm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation

Towards Subject and Diagnostic Identifiability in the Alzheimer’s Disease Spectrum Based on Functional Connectomes

Alzheimer’s disease (AD) is the only major cause of mortality in the world without an effective disease modifying treatment. Evidence supporting the so called “disconnection hypothesis” suggests that functional connectivity biomarkers may have clinical potential for early detection of AD. However, known issues with low test-retest reliability and signal to noise in functional connectivity may prevent accuracy and subsequent predictive capacity. We validate the utility of a novel principal component based diagnostic identifiability framework to increase separation in functional connectivity across the Alzheimer’s spectrum by identifying and reconstructing FC using only AD sensitive components or connectivity modes. We show that this framework (1) increases test-retest correspondence and (2) allows for better separation, in functional connectivity, of diagnostic groups both at the whole brain and individual resting state network level. Finally, we evaluate a posteriori the association between connectivity mode weights with longitudinal neurocognitive outcomes

Laser-UV-microirradiation of interphase nuclei and posttreatment with caffeine: a new approach to establish the arrangement of interphase chromosomes

Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus

CD43-independent augmentation of mouse T-cell function by glycoprotein cleaving enzymes

Previous work has shown that the function of mouse CD4 + T cells can be augmented by an enzyme, O -sialoglycoprotein endopeptidase (OSGE), which cleaves surface CD43, suggesting the idea that the high levels of glycosylated CD43 found on T cells from aged mice may contribute to immune senescence. New results now show that OSGE improves T-cell function even in mice lacking CD43, showing that other glycoproteins must contribute to the OSGE effect on function. Evaluation of other enzymes found two whose ability to stimulate CD4 activation was higher in aged than in young T cells. One of these, PNGase F, is a glycosidase specific for N-linked glycans, and the other, ST-Siase(2,3) from Salmonella typhimurium , is specific for α2,3-linked terminal sialic acid residues. Parallel lectin-binding experiments showed that removal of α2,3-linked sialic acid residues vulnerable to PNGase F and ST-Siase(2,3) was also greater in old than in young T cells. The preferential ability of PNGase F and ST-Siase(2,3) to improve the function of T cells from aged mice may involve cleavage of glycoproteins containing α2,3-linked sialic acid residues on N-linked or O-linked glycans or both.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75621/1/j.1365-2567.2006.02419.x.pd

A precision study of the fine tuning in the DiracNMSSM

Recently the DiracNMSSM has been proposed as a possible solution to reduce the fine tuning in supersymmetry. We determine the degree of fine tuning needed in the DiracNMSSM with and without non-universal gaugino masses and compare it with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed parameter regions we perform a precise calculation of the Higgs mass. In addition, we include the limits from direct SUSY searches and dark matter abundance. We find that both models are comparable in terms of fine tuning, with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure

Epistemic policy networks in the European Union’s CBRN risk mitigation policy

This paper offers insights into an innovative and currently flagship approach of the European Union (EU) to the mitigation of chemical, biological, radiological, and nuclear (CBRN) risks. Building on its long-time experience in the CBRN field, the EU has incorporated methods familiar to the students of international security governance: it is establishing regional networks of experts and expertise. CBRN Centers of Excellence, as they are officially called, aim to contribute to the security and safety culture in different parts of Africa, the Middle East, South East Asia, and South East Europe, in the broadly construed CBRN area. These regional networks represent a modern form of security cooperation, which can be conceptualized as an epistemic policy networks approach. It offers flexibility to the participating states, which have different incentives to get involved. At the same, however, the paper identifies potential limitations and challenges of epistemic policy networks in this form

Characterization of Imaging Luminance Measurement Devices (ILMDs)

CIE 244:2021This document describes the elements, function and characterization of imaging luminance measuring devices (ILMDs). Furthermore, the calibration of ILMDs is described and some guidelines for their use are provided. Using ILMDs the projection of the luminance distribution of a scene can be recorded and made available for further evaluation. In addition to a simple documentation of measurements, the geometrical assignment of the image points into the object coordinate system often allows more complex calculations by combining luminance, directional and, if necessary, solid angle information (e.g. for glare evaluation). In addition to the flexible evaluation option, it is possible to acquire a large number of measured values quickly and, if necessary, even synchronously. Furthermore, the type of evaluation can also be coupled to the image content, i.e. the image areas to be evaluated can be determined in the image either by their position within the image or by their luminance value

Ocean acidification shows negligible impacts on high-latitude bacterial community structure in coastal pelagic mesocosms

The impact of ocean acidification and carbonation on microbial community structure was assessed during a large-scale in situ costal pelagic mesocosm study, included as part of the EPOCA 2010 Arctic campaign. The mesocosm experiment included ambient conditions (fjord) and nine mesocosms, with pCO2 range from ~145 to ~1420 μatm. Samples collected at nine time points (t-1, t1, t5, t7, t12, t14, t22, t26 to t28) in seven treatments (ambient fjord (~145), 2×~185, ~270, ~685, ~820, ~1050 μatm) were analysed for "free-living" and "particle associated" microbial community composition using 16S rRNA amplicon sequencing. This high-throughput sequencing analysis produced ~20 000 000 16S rRNA V4 reads, which comprised 7000 OTUs. The main variables structuring these communities were, sample origin (fjord or mesocosms) and the filter size fraction (free-living or particle associated). The community was significantly different between the fjord and both the control and elevated 2 mesocosms (which were not significant different) after nutrients were added to the mesocosms; suggesting that the addition of nutrients is the primary driver of the change in mesocosm community structure. The relative importance of each structuring variable depended greatly on the time at which the community was sampled in relation to the phytoplankton bloom. The size fraction was the second most important factor for community structure; separating free-living from particle-associated bacteria. When free-living and particle-associated bacteria were analysed separately at different time points, the only taxon pCO2 was found to significantly affect were the Gammaproteobacteria after nutrient addition. Finally, pCO2 treatment was found to be significantly correlated (non-linear) with 15 rare taxa, most of which increased in abundance with higher CO2

Plucked human hair as a tissue in which to assess pharmacodynamic end points during drug development studies

We have demonstrated the feasibility of detecting and quantifying six cell-cycle-related nuclear markers (Ki67, pRb, p27, phospho-p27 (phosphorylated p27), phospho-pRb (phosphorylated pRb), phospho-HH3 (phosphorylated histone H3)) in plucked human scalp and eyebrow hair. Estimates of the proportion of plucked hairs that are lost or damaged during processing plus the intra- and intersubject variability of each nuclear marker with these techniques are provided to inform sizing decisions for intervention studies with drugs potentially impacting on these markers in the future