300 research outputs found
University Blockchain Research Initiative (UBRI): Boosting blockchain education and research
Get PDFSince its conceptualization, blockchain technology has witnessed continuous and rapid development, bringing profound changes to computer science, law, and economics. In 2008, the initial blockchain system was merely a growing list of records linked together using cryptography. Today, however, blockchains have become the foundation of most digital currencies, robust cloud computing platforms, and dependable databases for tracking supply chain information. Despite challenges and controversies, blockchain technology has the potential to help build a trustworthy and efficient digital world
Pauli's Principle in Probe Microscopy
Get PDFExceptionally clear images of intramolecular structure can be attained in
dynamic force microscopy through the combination of a passivated tip apex and
operation in what has become known as the "Pauli exclusion regime" of the
tip-sample interaction. We discuss, from an experimentalist's perspective, a
number of aspects of the exclusion principle which underpin this ability to
achieve submolecular resolution. Our particular focus is on the origins,
history, and interpretation of Pauli's principle in the context of interatomic
and intermolecular interactions.Comment: This is a chapter from "Imaging and Manipulation of Adsorbates using
Dynamic Force Microscopy", a book which is part of the "Advances in Atom and
Single Molecule Machines" series published by Springer
[http://www.springer.com/series/10425]. To be published late 201
Applying Digital Spatial Profiling of the Transcriptome to Elucidate Disease Mechanisms of Psychosis in Alzheimer’s disease
Get PDFBackground:
Psychosis occurs in 30-40% of individuals with AD. New insights into disease mechanisms may lead to novel pharmacological targets and treatments. Previous studies have focused on bulk tissue analysis with limited results. Digital spatial profiling (DSP) is a new technique for spatial analysis of RNA or proteins in fixed tissue. It allows quantitative profiling with spatial complexity to be collected from samples in a non-destructive manner. In this pilot study we used DSP to compare whole transcriptome data in amyloid beta and non-amyloid beta regions in participants with and without psychosis (AD+P; AD-P).
Method:
Six post-mortem brain samples from prefrontal cortex were provided by the Kings College London Brains for Dementia Research (BDR) brain bank. Frozen and formalin fixed, paraffin embedded (FFPE) sections were supplied in order to test the platform on each type. Psychosis positive and negative groups were selected based on Neuropsychiatric Inventory (NPI) assessments. Samples were hematoxylin and eosin (H&E) stained as well as stained with fluorescent antibodies for AT8, NeuN, SYTO13 and Aβ. Regions of interest (ROIs) are selected based on morphology markers and tissue morphology (see Figure 1 for Amyloid ROI selection).
Result:
H&E staining revealed the frozen samples to be too badly degraded so the analysis was conducted on FFPE sections. AT8 staining showed widespread tau pathology to the extent that it was not possible to confidently select non-tau ROIs. Analysis of Aβ plaque containing and Aβ plaque free regions, comparing AD+P and AD-P groups, found 314 differentially expressed genes in plaque free regions, and 172 differentially expressed genes in plaque containing regions (Figure 2). Of these 172 genes, 28 were not differentially expressed in plaque free regions, forming a plaque-specific signature of genes differentially expressed in AD+P.
Conclusion:
This pilot study demonstrates the potential of the NanoString GeoMx™ DSP platform as an innovative spatial transcriptomics methodology for investigating AD+P with the potential to uncover differentially expressed genes that may be missed by bulk RNA sequencing studies. FFPE sections appear to be optimal. Analysing earlier stage disease and more sections per subject may help with better differentiation of tau and non-tau ROIs
New project to support scientific collaboration electronically
Full text linkPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95417/1/eost10181.pd
Unique determination of “subatomic” contrast by imaging covalent backbonding
Get PDFThe origin of so-called “subatomic” resolution in dynamic force microscopy has remained controversial since its first observation in 2000. A number of detailed experimental and theoretical studies have identified different possible physicochemical mechanisms potentially giving rise to subatomic contrast. In this study, for the first time we are able to assign the origin of a specific instance of subatomic contrast as being due to the back bonding of a surface atom in the tip−sample junction
Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: A DNA co-methylation network analysis
Get PDFData availability:
DNA methylation data used in this study was provided for the study by the authors of a previous publication45. It is available via figshare https://doi.org/10.17035/cardiff.27195645.v1. Data used in the preparation of this article were obtained on 1st June 2020 from the Parkinson’s Progression Markers Initiative (PPMI) database (https://www.ppmi-info.org/access-data-specimens/download-data), RRID:SCR_006431. This analysis used data openly available from PPMI. For up-to-date information on the study, visit http://www.ppmi-info.org.Code availability:
All codes are available at https://github.com/JoshHarveyGit/PD_TraitNetworkAnalysis.Supplementary information is available online at: https://www.nature.com/articles/s41531-025-00877-5#Sec18 .Parkinson’s disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinson’s disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. Of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regards to depressive symptoms in Parkinson’s disease.This work was funded by research grants from the Medical Research Council (MRC (MR/S011625/1), the National Institute of Aging (NIA) of the National Institutes of Health (NIH) (R01AG067015), BRACE and the Charles Wolfson Charitable Trust to KL and from Parkinson’s UK (Project Grants G-1309 and G-1502) to NW. This study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre
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Understanding disability glare: light scatter and retinal illuminance as predictors of sensitivity to contrast
Get PDFThe presence of a bright light in the visual field has two main effects on the retinal image: reduced contrast and increased retinal illuminance due to scattered light; the latter can, under some conditions, lead to an improvement in retinal sensitivity. The combined effect remains poorly understood, particularly at low light levels. A psychophysical flicker-cancellation test was used to measure the amount and angular distribution of scattered light in the eye for 40 observers. Contrast thresholds were measured using a functional contrast sensitivity test. Pupil-plane glare-source illuminances (i.e. 0, 1.35, 19.21 lm/m2), eccentricities (5°, 10°, 15°), and background luminances (1, 2.6, 26 cd/m2) were investigated. Visual performance was better than predicted, based on loss of retinal image contrast caused by scattered light, particularly in the mesopic range. Prediction accuracy improved significantly when the expected increase in retinal sensitivity in the presence of scattered light was also incorporated in the model
High-precision measurements of low-lying isomeric states in In with JYFLTRAP double Penning trap
Full text linkNeutron-rich In isotopes have been studied utilizing the double
Penning trap mass spectrometer JYFLTRAP at the IGISOL facility. Using the
phase-imaging ion-cyclotron-resonance technique, the isomeric states were
resolved from ground states and their excitation energies measured with high
precision in In. In In, the states were
separated and their masses were measured while the energy difference between
the unresolved and states, whose presence was confirmed by
post-trap decay spectroscopy was determined to be keV. In addition,
the half-life of Cd, s, was extracted.
Experimental results were compared with energy density functionals, density
functional theory and shell-model calculations.Comment: 11 pages, 7 figure
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