Medipix3 Demonstration and understanding of near ideal detector performance for 60 & 80 keV electrons

In our article we report first quantitative measurements of imaging performance for the current generation of hybrid pixel detector, Medipix3, as direct electron detector. Utilising beam energies of 60 & 80 keV, measurements of modulation transfer function (MTF) and detective quantum efficiency (DQE) have revealed that, in single pixel mode (SPM), energy threshold values can be chosen to maximize either the MTF or DQE, obtaining values near to, or even exceeding, those for an ideal detector. We have demonstrated that the Medipix3 charge summing mode (CSM) can deliver simultaneous, near ideal values of both MTF and DQE. To understand direct detection performance further we have characterized the detector response to single electron events, building an empirical model which can predict detector MTF and DQE performance based on energy threshold. Exemplifying our findings we demonstrate the Medipix3 imaging performance, recording a fully exposed electron diffraction pattern at 24-bit depth and images in SPM and CSM modes. Taken together our findings highlight that for transmission electron microscopy performed at low energies (energies <100 keV) thick hybrid pixel detectors provide an advantageous and alternative architecture for direct electron imagin

Detectors—The ongoing revolution in scanning transmission electron microscopy and why this important to material characterization

Detectors are revolutionizing possibilities in scanning transmission electron microscopy because of the advent of direct electron detectors that record at a high quantum efficiency and with a high frame rate. This allows the whole back focal plane to be captured for each pixel in a scan and the dataset to be processed to reveal whichever features are of interest. There are many possible uses for this advance of direct relevance to understanding the nano- and atomic-scale structure of materials and heterostructures. This article gives our perspective of the current state of the field and some of the directions where it is likely to go next. First, a wider overview of the recent work in this area is given before two specific examples of its application are given: one is imaging strain in thin films and the other one is imaging changes in periodicity along the beam direction as a result of the formation of an ordered structure in an epitaxial thin film. This is followed by an outlook that presents future possible directions in this rapidly expanding field

A Targeted Sampling Strategy for Compressive Cryo Focused Ion Beam Scanning Electron Microscopy

Cryo Focused Ion-Beam Scanning Electron Microscopy (cryo FIB-SEM) enables three-dimensional and nanoscale imaging of biological specimens via a slice and view mechanism. The FIB-SEM experiments are, however, limited by a slow (typically, several hours) acquisition process and the high electron doses imposed on the beam sensitive specimen can cause damage. In this work, we present a compressive sensing variant of cryo FIB-SEM capable of reducing the operational electron dose and increasing speed. We propose two Targeted Sampling (TS) strategies that leverage the reconstructed image of the previous sample layer as a prior for designing the next subsampling mask. Our image recovery is based on a blind Bayesian dictionary learning approach, i.e., Beta Process Factor Analysis (BPFA). This method is experimentally viable due to our ultra-fast GPU-based implementation of BPFA. Simulations on artificial compressive FIB-SEM measurements validate the success of proposed methods: the operational electron dose can be reduced by up to 20 times. These methods have large implications for the cryo FIB-SEM community, in which the imaging of beam sensitive biological materials without beam damage is crucial.Comment: Submitted to ICASSP 202

Markers of neuroinflammation associated with Alzheimer's disease pathology in older adults.

In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i.e. an AD CSF biomarker profile) and to investigate associations of inflammation markers with CSF biomarkers of amyloid, tau pathology, and neuronal injury. Cross-sectional analysis was performed on data from 120 older community-dwelling adults with normal cognition (n=48) or with cognitive impairment (n=72). CSF Aβ1-42, tau and p-tau181, and a panel of 37 neuroinflammatory markers in both CSF and serum were quantified. Least absolute shrinkage and selection operator (LASSO) regression was applied to determine a reference model that best predicts an AD CSF biomarker profile defined a priori as p-tau181/Aβ1-42 ratio &gt;0.0779. It was then compared to a second model that included the inflammatory markers from either serum or CSF. In addition, the correlations between inflammatory markers and CSF Aβ1-42, tau and p-tau181 levels were assessed. Forty-two subjects met criteria for having an AD CSF biomarker profile. The best predictive models included 8 serum or 3 CSF neuroinflammatory markers related to cytokine mediated inflammation, vascular injury, and angiogenesis. Both models improved the accuracy to predict an AD biomarker profile when compared to the reference model. In analyses separately performed in the subgroup of participants with cognitive impairment, adding the serum or the CSF neuroinflammation markers also improved the accuracy of the diagnosis of AD pathology. None of the inflammatory markers correlated with the CSF Aβ1-42 levels. Six CSF markers (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the CSF tau and p-tau181 levels, and these associations remained significant after controlling for age, sex, cognitive impairment, and APOEε4 status. The identified serum and CSF neuroinflammation biomarker signatures improve the accuracy of classification for AD pathology in older adults. Our results suggest that inflammation, vascular injury, and angiogenesis as reflected by CSF markers are closely related to cerebral tau pathology

Quantifying the Performance of a Hybrid Pixel Detector with GaAs:Cr Sensor for Transmission Electron Microscopy

Hybrid pixel detectors (HPDs) have been shown to be highly effective for diffraction-based and time-resolved studies in transmission electron microscopy, but their performance is limited by the fact that high-energy electrons scatter over long distances in their thick Si sensors. An advantage of HPDs compared to monolithic active pixel sensors (MAPS) is that their sensor does not need to be fabricated from Si. We have compared the performance of the Medipix3 HPD with a Si sensor and with a GaAs:Cr sensor using primary electrons in the energy range of 60 - 300keV. We describe the measurement and calculation of the detectors' modulation transfer function (MTF) and detective quantum efficiency (DQE), which show that the performance of the GaAs:Cr device is markedly superior to that of the Si device for high-energy electrons.Comment: 15 pages + references, 13 figure

The Potential of Subsampling and Inpainting for Fast Low-Dose Cryo FIB-SEM Imaging and Tomography

Traditional image acquisition for cryo focused ion-beam scanning electron microscopy tomography often sees thousands of images being captured over a period of many hours, with immense data sets being produced. When imaging beam sensitive materials, these images are often compromised by additional constraints related to beam damage and the devitrification of the material during imaging, which renders data acquisition both costly and unreliable. Subsampling and inpainting are proposed as solutions for both of these aspects, allowing fast and low-dose imaging to take place in the FIB-SEM without an appreciable low in image quality. In this work, experimental data is presented which validates subsampling and inpainting as a useful tool for convenient and reliable data acquisition in a FIB-SEM, with new methods of handling 3-dimensional data being employed in context of dictionary learning and inpainting algorithms using a newly developed microscope control software and data recovery algorithm.Comment: In submission to "Microscopy and Microanalysis" journal. Authorship reviewed from previous submissio

The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS

GLP-1 receptor agonists used for the treatment of diabetes, have shown some neuroprotective effects in cellular and animal models of Alzheimer’s disease (AD) and Parkinson’s disease (PD). There are currently few studies investigating GLP-1 receptor agonists in the treatment of ALS, where these neuroprotective effects may be beneficial. Here we investigate the effects of liraglutide, a GLP-1 receptor agonist, in two well characterised transgenic mouse models of ALS (SOD1G93A and TDP-43Q331K) to determine if liraglutide could be a potential treatment in ALS patients. Doses of liraglutide previously shown to have efficacy in AD and PD mouse models were used. Behavioural testing was carried out to ascertain the effect of liraglutide on disease progression. Immunohistochemical analysis of tissue was used to determine any neuroprotective effects on the CNS. We found that liraglutide dosed animals showed no significant differences in disease progression when compared to vehicle dosed animals in either the SOD1G93A or TDP-43Q331K mouse models of ALS. We also observed no changes in motor neuron counts or glial activation in lumbar spinal cords of liraglutide treated mice compared to vehicle dosed mice. Overall, we found no evidence to support clinical evaluation of liraglutide as a potential candidate for the treatment of ALS

Wax: A benign hydrogen-storage material that rapidly releases H2-rich gases through microwave-assisted catalytic decomposition

Hydrogen is often described as the fuel of the future, especially for application in hydrogen powered fuel-cell vehicles (HFCV’s). However, its widespread implementation in this role has been thwarted by the lack of a lightweight, safe, on-board hydrogen storage material. Here we show that benign, readily-available hydrocarbon wax is capable of rapidly releasing large amounts of hydrogen through microwave-assisted catalytic decomposition. This discovery offers a new material and system for safe and efficient hydrogen storage and could facilitate its application in a HFCV. Importantly, hydrogen storage materials made of wax can be manufactured through completely sustainable processes utilizing biomass or other renewable feedstocks

Estudo de caso : avaliação do impacto no desempenho e satisfação da força de trabalho com a reestruturação organizacional do departamento de gestão integrada (DGI) - UFRGS

A administração pública no Brasil é um tema bastante estudado e criticado por diversos autores, pois ainda está imersa em dúvidas acerca das melhores governanças, práticas de gestão e estruturas organizacionais que impactem positivamente o desempenho e, consequentemente, promova o crescimento e vigor dessas instituições. O setor da administração pública em nosso país é constantemente criticado pela disfunção da burocracia pertinente ao sistema, bem como a dificuldade de acompanhar as mudanças que são vivenciadas pelo setor privado, por exemplo. No presente trabalho, é realizado um estudo de caso no Departamento de Gestão Integrada (DGI) da PROPLAN – UFRGS (Universidade Federal do Rio Grande do Sul), que passou por mudanças na sua atuação e função como departamento perante a instituição. As modificações que foram propostas ao departamento podem ser divididas em dois campos. O primeiro em relação à orientação e função do departamento como um todo, que também influenciou uma mudança de mesmo teor em suas divisões internas. O segundo campo, pelo qual as modificações passaram, é o da força de trabalho, ou seja, pessoas. Em outras palavras, uma realocação de funções que promovesse um melhor aproveitamento das competências dos membros foi promovida. O presente estudo traça um paralelo entre o período anterior as modificações em contraste com o período após as modificações, verificando, junto ao departamento, questões ligadas ao desempenho e satisfação das pessoas que trabalham nesse espaço. Com os resultados, foi possível concluir que houve um aumento na satisfação geral dos membros, bem como aspectos relativos ao desempenho foram impactados positivamente pelas mudanças promovidas no DGI.Public administration in Brazil is a theme widely studied and criticized by authors in this area, because it stills immerged in doubts concerning the best managing practices, governance and organizational structures that impact positively the performance and, as a result, generate growth in this kind of institutions. The public administration sector in Brazil is constantly criticized by its burocracy disfunction related to the system it is involved, as well as a strong effort to be up to date with the changes that happen in the private sector of the economy. In this study, its presented a case study in the “Departamento de Gestão Integrada - (DGI)” which can be understood as the department responsible for the strategy deployment in the institution, that has been under several changes in its function an operation towards the university (Universidade Federal do Rio Grande do Sul – UFRGS). The changes on the department can be split in two, in order to be easily understood. The first is related to the orientation and function of the entire department, that influenced changes in its intern divisions. The second point in which the changes went through is people functions in the department. In other words, shifts in personal roles in the department aiming a better exploitation of each ones capacities and competences was implemented. This case study draws a parallel between the period before the changes and after them, verifying issues linked to the department’s overall performance and personal satisfaction with the role each person has in the organization. Analyzing the results, it was possible to conclude an increase in people satisfaction and aspects related to the department’s performance

Regional zircon U-Pb geochronology for the Maniitsoq region, southwest Greenland

The Ministry of Mineral Resources, Government of Greenland, funded this project. Analyses in the JdLC GeoHistory Facility were enabled by instrumentation supported by AuScope (auscope.org.au) and the Australian Government via the National Collaborative Research Infrastructure Strategy. The Tescan Mira3 FEG-SEM was funded through the Australian Research Council LIEF program.Zircon U-Pb geochronology places high-temperature geological events into temporal context. Here, we present a comprehensive zircon U-Pb geochronology dataset for the Meso- to Neoarchean Maniitsoq region in southwest Greenland, which includes the Akia Terrane, Tuno Terrane, and the intervening Alanngua Complex. The magmatic and metamorphic processes recorded in these terranes straddle a key change-point in early Earth geodynamics. This dataset comprises zircon U-Pb ages for 121 samples, including 46 that are newly dated. A principal crystallization peak occurs across all three terranes at ca. 3000 Ma, with subordinate crystallization age peaks at 3200 Ma (Akia Terrane and Alanngua Complex only), 2720 Ma and 2540 Ma. Metamorphic age peaks occur at 2990 Ma, 2820-2700 Ma, 2670-2600 Ma and 2540 Ma. Except for one sample, all dated metamorphic zircon growth after the Neoarchean occurred in the Alanngua Complex or within 20 km of its boundaries. This U-Pb dataset provides an important resource for addressing Earth Science topics as diverse as crustal evolution, fluid-rock interaction and mineral deposit genesis.Publisher PDFPeer reviewe