Lower limb hyperthermia augments functional hyperaemia during small muscle mass exercise similarly in trained elderly and young humans

Data availability statement: The raw, unidentified data collected throughout this study will be made available via Brunel Figshare, an online data repository database.Copyright © 2023 The Authors. New Findings: What is the central question of the study? Ageing is postulated to lead to underperfusion of human limb tissues during passive and exertional hyperthermia, but findings to date have been equivocal. Thus, does age have an independent adverse effect on local haemodynamics during passive single-leg hyperthermia, single-leg knee-extensor exercise and their combination? What is the main finding and its importance? Local hyperthermia increased leg blood flow over three-fold and had an additive effect during knee-extensor exercise with no absolute differences in leg perfusion between the healthy, exercise-trained elderly and the young groups. Our findings indicate that age per se does not compromise lower limb hyperaemia during local hyperthermia and/or small muscle mass exercise. Heat and exercise therapies are recommended to improve vascular health across the lifespan. However, the haemodynamic effects of hyperthermia, exercise and their combination are inconsistent in young and elderly people. Here we investigated the acute effects of local-limb hyperthermia and exercise on limb haemodynamics in nine healthy, trained elderly (69 ± 5 years) and 10 young (26 ± 7 years) adults, hypothesising that the combination of local hyperthermia and exercise interact to increase leg perfusion, albeit to a lesser extent in the elderly. Participants underwent 90 min of single whole-leg heating, with the contralateral leg remaining as control, followed by 10 min of low-intensity incremental single-leg knee-extensor exercise with both the heated and control legs. Temperature profiles and leg haemodynamics at the femoral and popliteal arteries were measured. In both groups, heating increased whole-leg skin temperature and blood flow by 9.5 ± 1.2°C and 0.7 ± 0.2 L min−1 (>3-fold), respectively (P < 0.0001). Blood flow in the heated leg remained 0.7 ± 0.6 and 1.0 ± 0.8 L min−1 higher during exercise at 6 and 12 W, respectively (P < 0.0001). However, there were no differences in limb haemodynamics between cohorts, other than the elderly group exhibiting a 16 ± 6% larger arterial diameter and a 51 ± 6% lower blood velocity following heating (P < 0.0001). In conclusion, local hyperthermia-induced limb hyperperfusion and/or small muscle mass exercise hyperaemia are preserved in trained older people despite evident age-related structural and functional alterations in their leg conduit arteries.This study was completed without external funding

Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice

A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy

Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. An early analysis noted that dwarf galaxies may not be isotropically distributed around our Galaxy, as several are correlated with streams of HI emission, and possibly form co-planar groups. These suspicions are supported by recent analyses, and it has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence (99.998% significance) of a planar sub-group of satellites in the Andromeda galaxy, comprising approximately 50% of the population. The structure is vast: at least 400 kpc in diameter, but also extremely thin, with a perpendicular scatter <14.1 kpc (99% confidence). Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This finding shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum, a new insight for our understanding of the origin of these most dark matter dominated of galaxies. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and is co-planar with the Milky Way to Andromeda position vector. The existence of such extensive coherent kinematic structures within the halos of massive galaxies is a fact that must be explained within the framework of galaxy formation and cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1 three-dimensional interactive figure. To view and manipulate the 3-D figure, an Adobe Reader browser plug-in is required; alternatively save to disk and view with Adobe Reade

UV-sensitive wearable devices for colorimetric monitoring of UV exposure

The extensive exposure of the human epidermis to solar radiation creates a health risk that results in skin cancer. Commercial sunscreens offer sufficient protection from ultraviolet (UV) radiation; however, the ability to determine UV exposure limits can provide informed decisions about the dose of sunscreen required and the frequency of re-application. Here, a wide range of wearable devices that colorimetrically report on UV exposure are developed. Under UV radiation, UV-sensitive dyes change their color from 280 to 400 nm in the visible spectrum. By correlating the current color value and the UV dose, the amount of sun exposure is determined with an accuracy of 95%. A smartphone camera algorithm is coded to automatically perform the color analysis of these dyes. The UV-sensitive dyes are incorporated in wearable devices, skin patches, textiles, contact lenses, and tattoo inks. The developed wearable devices will ensure monitoring UV radiation to rationally manage the user's behavior in order to prevent harmful sun exposure

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Low-pass filtering compensation in common-path digital holographic microscopy

A low-pass filtering compensation (LPFC) method is proposed to compensate for phase aberrations in point diffraction-based common-path digital holographic microscopy. This method estimates the phase aberration from the object hologram by Fourier transform and low-pass spatial filtering. The estimated phase aberration is subtracted from the object phase image to achieve single-hologram phase compensation. The accuracy and capability of LPFC for phase compensation were demonstrated by experiments on a Ronchi grating and a human blood smear. LPFC provides phase compensation for both smooth objects and objects containing abrupt edges, in the special case of a system with relatively high-frequency objects and low-frequency slight phase aberrations. LPFC operates without the need for fitting procedures, iterative steps, or prior knowledge of the optical parameters, which substantially simplifies the process of phase compensation in quantitative phase imaging. Digital holographic microscopy (DHM) has been developed for a wide range of applications in the examination of cell pathophysiology,1,2 semiconductors,3 and 2D materials.4 Common-path DHM combines common-path geometry and off-axis holography, and hence, it provides subnanometer level optical phase delay (OPD) imaging with high temporal stability and the acquisition speed is limited only by the detector.5–8 Point diffraction-based common-path DHM uses a spatial filter to generate holograms with uniform reference fields, resulting in a compact system with a full field of view (FOV).9–13 In these setups, the zeroth-order beam is low-pass filtered by a pinhole in the Fourier plane of the spatial filtering lens, which is generally assumed to be a uniform field at the surface of the image sensor.11,13 However, due to the use of a microscope objective (MO) and the complex spatial filter, or a non-optimal imaging system, the zeroth-order beam can be distorted, which introduces phase aberrations to the original off-axis holograms. An automatic aberration compensation is desirable to extract the sample phase images. Various approaches have been proposed to estimate the phase aberrations in DHM. Commonly used double-exposure compensation (DEC) relies on the manual double-exposure operation,14 allowing a calibration of the DHM setup from the second specimen-free hologram. This method requires that the wavefronts of the specimen-free hologram and the specimen hologram are parallel to each other strictly. Zernike polynomial fitting (ZPF) calculates the phase aberration through numerical processing such as computational fitting procedures, which requires prior knowledge about the optical parameters, or iterative procedures15–17 Methods based on a deep learning convolutional neural network (CNN),18 phase variation minimization,19 sparse optimization,20 and synthetic difference21 use complex algorithms to estimate residual aberrations. The self-overlapping approach has been applied without fitting procedures, but it limits the FOV due to the overlapping operations.22 The concept of self-reference conjugated hologram (self-RCH) was introduced for the phase compensation of smooth objects in a modified Mach–Zehnder interferometer.23 However, its accuracy is still to be demonstrated quantitatively. In this Letter, a low-pass filtering compensation (LPFC) method is proposed to compensate for phase aberrations of both smooth objects and objects with abrupt edges in point diffraction-based common-path DHM, which generates holograms with relatively high-frequency objects and low-frequency slight phase aberrations (the phase contribution due to the aberrations of the whole hologram is less than 10 rad). The capability and accuracy of LPFC are quantitatively proved by the compensation results of a Ronchi grating with abrupt edges and a human blood smear. LPFC requires no fitting procedures, iterative steps, or prior knowledge of the optical parameters, which substantially simplifies the process of phase compensation in quantitative phase imaging. The schematic of the experimental setup is shown in Fig. 1. A He–Ne laser beam (632 nm, 0.8 mW, HNLS008R-EC, Thorlabs) was expanded and collimated for plane illumination. M1, M2, BE1, and C1 were used to provide illumination in transmission mode. BS1, BE2, C2, and BS2 were for illumination in reflection mode. An infinity-corrected MO (NA = 0.25, Plan N, Olympus) was used to produce a magnified image of the sample. TL was used to collimate the light from MO. G (40 c/mm, Applied Image Inc.) was placed at the image plane to separate the magnified image field into multiple orders. L (f = 100 mm) was used for imaging and spatial filtering simultaneously. The multiple order image fields were isolated in the Fourier plane (the back focal plane) of L, where SF was placed. SF allowed for passing the entire zeroth diffraction order beam, which was used as the sample field. The first order was physically low-pass filtered by a pinhole, which was used as the reference field. All the other diffraction orders were blocked. A CMOS camera (1280 × 1024 pixels, monochrome sensor, DCC1545M, Thorlabs) was used as the detector

Thresholds of large N factorization in CFT4: exploring bulk spacetime in AdS(5)

52 pages, 6 figures52 pages, 6 figure

Efimov effect in quantum magnets

Physics is said to be universal when it emerges regardless of the underlying microscopic details. A prominent example is the Efimov effect, which predicts the emergence of an infinite tower of three-body bound states obeying discrete scale invariance when the particles interact resonantly. Because of its universality and peculiarity, the Efimov effect has been the subject of extensive research in chemical, atomic, nuclear and particle physics for decades. Here we employ an anisotropic Heisenberg model to show that collective excitations in quantum magnets (magnons) also exhibit the Efimov effect. We locate anisotropy-induced two-magnon resonances, compute binding energies of three magnons and find that they fit into the universal scaling law. We propose several approaches to experimentally realize the Efimov effect in quantum magnets, where the emergent Efimov states of magnons can be observed with commonly used spectroscopic measurements. Our study thus opens up new avenues for universal few-body physics in condensed matter systems.Comment: 7 pages, 5 figures; published versio

Self-Organized Hydrodynamics with congestion and path formation in crowds

A continuum model for self-organized dynamics is numerically investigated. The model describes systems of particles subject to alignment interaction and short-range repulsion. It consists of a non-conservative hyperbolic system for the density and velocity orientation. Short-range repulsion is included through a singular pressure which becomes infinite at the jamming density. The singular limit of infinite pressure stiffness leads to phase transitions from compressible to incompressible dynamics. The paper proposes an Asymptotic-Preserving scheme which takes care of the singular pressure while preventing the breakdown of the CFL stability condition near congestion. It relies on a relaxation approximation of the system and an elliptic formulation of the pressure equation. Numerical simulations of impinging clusters show the efficiency of the scheme to treat congestions. A two-fluid variant of the model provides a model of path formation in crowds

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine