ORCID Profile
0000-0003-1550-2276
Current Organisations
Australian National University
,
University of Tasmania
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Publisher: American Physical Society (APS)
Date: 25-05-2022
Publisher: Informa UK Limited
Date: 07-2019
DOI: 10.2147/COPD.S208428
Publisher: Cold Spring Harbor Laboratory
Date: 19-06-2022
DOI: 10.1101/2022.06.17.496569
Abstract: Heterogenous fluid shear stress is known to provide mechanical cues for cell adhesion and translocation. To assemble 3D microstructures using current fabrication methods in a single channel and recapitulate in vivo heterogenous fluid flow would require hours of fabrication and specialized equipment. Inspired by the traditional art form of inside painting, we developed a technique for 3D fabrication of micro-patterned flow channels and mixed in vivo fluid flow in a matter of minutes. We termed this technique Multiphoton Inner Laser Lithography (MILL). We further showed that when combined with adaptive optics, MILL is compatible with both flat and curved channel shapes. MILL recapitulated in vivo tissue topology and 3D fluid flow within tissue stroma (low fluid shear, 0 - 3.5 dynes/cm2) and blood vessel (high fluid shear, 0 - 80 dynes/cm2). We demonstrate fibroblast cell and platelets adhere and translocate differently between laminar flow patterns that are homogenous versus heterogeneous in real time. Parallel strips of MILL channels were assembled for simultaneous platelet function test to quantify the efficacy of an antithrombotic GPVI Fab (~2000 microthrombi per test). The MILL technique can be readily reproduced in vivo fluid flow in minutes and benefit preclinical screening of drug pharmacokinetics.
Publisher: Springer Science and Business Media LLC
Date: 05-2022
DOI: 10.1140/EPJC/S10052-022-10217-Z
Abstract: This paper presents an analysis at next-to-next-to-leading order in the theory of quantum chromodynamics for the determination of a new set of proton parton distribution functions using erse measurements in pp collisions at $$\\sqrt{s} = 7$$ s = 7 , 8 and 13 TeV, performed by the ATLAS experiment at the Large Hadron Collider, together with deep inelastic scattering data from ep collisions at the HERA collider. The ATLAS data sets considered are differential cross-section measurements of inclusive $$W^{\\pm }$$ W ± and $$Z/\\gamma ^*$$ Z / γ ∗ boson production, $$W^{\\pm }$$ W ± and Z boson production in association with jets, $$t\\bar{t}$$ t t ¯ production, inclusive jet production and direct photon production. In the analysis, particular attention is paid to the correlation of systematic uncertainties within and between the various ATLAS data sets and to the impact of model, theoretical and parameterisation uncertainties. The resulting set of parton distribution functions is called ATLASpdf21.
Publisher: Informa UK Limited
Date: 31-12-2015
Publisher: Cold Spring Harbor Laboratory
Date: 29-07-2020
DOI: 10.1101/2020.07.26.20162248
Abstract: COVID-19 is complicated by acute lung injury, and death in some in iduals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter airway epithelial cells (AECs). To determine what factors are associated with ACE2 expression particularly in patients with asthma and chronic obstructive pulmonary disease (COPD). We obtained upper and lower AECs from 145 people from two independent cohorts, aged 2-89, Newcastle (n=115), and from Perth (n= 30) Australia. The Newcastle cohort was enriched with people with asthma (n=37) and COPD (n=38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry were assessed by quantitative PCR, protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AECs. Increased gene expression of ACE2 was associated with older age (p=0.02) and male sex (p=0.03), but not pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma (p=0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in asthma (p=0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface was increased (p=0.02). ACE2 protein levels were lower in endobronchial biopsies from asthma patients. Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications. ACE2 is the primary receptor for SARS-COV-2. We demonstrate that lower airway expression of ACE2 is increased in older adults and males. We also find that lower ACE2 expression in epithelial cells occurs in people with asthma and is associated with reduced Furin expression and increased ADAM-17 expression. This may explain at least in part the relative sparing of people with asthma from severe COVID-19 disease.
Publisher: Springer Science and Business Media LLC
Date: 2022
DOI: 10.1140/EPJC/S10052-021-09843-W
Abstract: A technique is presented to measure the efficiency with which c -jets are mistagged as b -jets (mistagging efficiency) using $$t\\bar{t}$$ t t ¯ events, where one of the W bosons decays into an electron or muon and a neutrino and the other decays into a quark–antiquark pair. The measurement utilises the relatively large and known $$W\\rightarrow cs$$ W → c s branching ratio, which allows a measurement to be made in an inclusive c -jet s le. The data s le used was collected by the ATLAS detector at $$\\sqrt{s} = 13$$ s = 13 $$\\text {TeV}$$ TeV and corresponds to an integrated luminosity of 139 fb $$^{-1}$$ - 1 . Events are reconstructed using a kinematic likelihood technique which selects the mapping between jets and $$t\\bar{t}$$ t t ¯ decay products that yields the highest likelihood value. The distribution of the b -tagging discriminant for jets from the hadronic W decays in data is compared with that in simulation to extract the mistagging efficiency as a function of jet transverse momentum. The total uncertainties are in the range 3–17%. The measurements generally agree with those in simulation but there are some differences in the region corresponding to the most stringent b -jet tagging requirement.
Publisher: American Chemical Society (ACS)
Date: 26-12-2019
DOI: 10.1021/ACS.BIOCHEM.8B01231
Abstract: The heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of l-tryptophan oxidation along the kynurenine pathway. IDO1 is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Here we demonstrate that IDO1 is a mammalian nitrite reductase capable of chemically reducing nitrite to nitric oxide (NO) under hypoxia. Ultraviolet-visible absorption and resonance Raman spectroscopy showed that incubation of dithionite-reduced, ferrous-IDO1 protein (Fe
Publisher: American Thoracic Society
Date: 08-2020
Publisher: MDPI AG
Date: 15-05-2020
DOI: 10.3390/IJMS21103498
Abstract: T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of ζ-chain in a light controlled manner. We showed that spatial clustering of the ζ-chain intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of ζ-chain, Zap70, PLCγ, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate ζ-chain phosphorylation upon ζ-chain clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed ζ-chain clusters at the plasma membrane. Taken together, our data demonstrated the biophysical relevance of receptor clustering in TCR signaling.
Publisher: Cold Spring Harbor Laboratory
Date: 19-02-2020
DOI: 10.1101/2020.02.17.953463
Abstract: T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of CD3ζ chains in a light controlled manner. We showed that spatial clustering of the CD3ζ intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of CD3ζ, Zap70, PLCγ, ERK and initiated Ca 2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate CD3ζ phosphorylation upon CD3ζ clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3ζ clusters at the plasma membrane. Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.
Publisher: Elsevier BV
Date: 06-2022
Publisher: American Physical Society (APS)
Date: 06-09-2022
Publisher: American Physical Society (APS)
Date: 11-05-2022
Publisher: Springer Science and Business Media LLC
Date: 11-07-2022
DOI: 10.1140/EPJC/S10052-022-10489-5
Abstract: A search for long-lived charginos produced either directly or in the cascade decay of heavy prompt gluino states is presented. The search is based on proton–proton collision data collected at a centre-of-mass energy of $$\\sqrt{s}$$ s = 13 T $$\\text {eV}$$ eV between 2015 and 2018 with the ATLAS detector at the LHC, corresponding to an integrated luminosity of 136 fb $$^{-1}$$ - 1 . Long-lived charginos are characterised by a distinct signature of a short and then disappearing track, and are reconstructed using at least four measurements in the ATLAS pixel detector, with no subsequent measurements in the silicon-microstrip tracking volume nor any associated energy deposits in the calorimeter. The final state is complemented by a large missing transverse-momentum requirement for triggering purposes and at least one high-transverse-momentum jet. No excess above the expected backgrounds is observed. Exclusion limits are set at 95% confidence level on the masses of the chargino and gluino for different chargino lifetimes. Chargino masses up to 660 (210) G $$\\text {eV}$$ eV are excluded in scenarios where the chargino is a pure wino (higgsino). For charginos produced during the cascade decay of a heavy gluino, gluinos with masses below 2.1 T $$\\text {eV}$$ eV are excluded for a chargino mass of 300 G $$\\text {eV}$$ eV and a lifetime of 0.2 ns.
Publisher: Frontiers Media SA
Date: 31-01-2020
Publisher: American Physical Society (APS)
Date: 11-05-2022
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: American Thoracic Society
Date: 02-2022
Publisher: Frontiers Media SA
Date: 12-01-2021
Publisher: Springer Science and Business Media LLC
Date: 08-08-2022
Abstract: A direct search for Higgs bosons produced via vector-boson fusion and subsequently decaying into invisible particles is reported. The analysis uses 139 fb − 1 of pp collision data at a centre-of-mass energy of $$ \\sqrt{s} $$ s = 13 TeV recorded by the ATLAS detector at the LHC. The observed numbers of events are found to be in agreement with the background expectation from Standard Model processes. For a scalar Higgs boson with a mass of 125 GeV and a Standard Model production cross section, an observed upper limit of 0 . 145 is placed on the branching fraction of its decay into invisible particles at 95% confidence level, with an expected limit of 0 . 103. These results are interpreted in the context of models where the Higgs boson acts as a portal to dark matter, and limits are set on the scattering cross section of weakly interacting massive particles and nucleons. Invisible decays of additional scalar bosons with masses from 50 GeV to 2 TeV are also studied, and the derived upper limits on the cross section times branching fraction decrease with increasing mass from 1 . 0 pb for a scalar boson mass of 50 GeV to 0 . 1 pb at a mass of 2 TeV.
Publisher: Springer Science and Business Media LLC
Date: 11-2021
Abstract: A measurement of prompt photon-pair production in proton-proton collisions at $$ \\sqrt{s} $$ s = 13 TeV is presented. The data were recorded by the ATLAS detector at the LHC with an integrated luminosity of 139 fb − 1 . Events with two photons in the well-instrumented region of the detector are selected. The photons are required to be isolated and have a transverse momentum of $$ {p}_{\\mathrm{T}{,}_{\\gamma 1(2)}} $$ p T , γ 1 2 40 (30) GeV for the leading (sub-leading) photon. The differential cross sections as functions of several observables for the diphoton system are measured and compared with theoretical predictions from state-of-the-art Monte Carlo and fixed-order calculations. The QCD predictions from next-to-next-to-leading-order calculations and multi-leg merged calculations are able to describe the measured integrated and differential cross sections within uncertainties, whereas lower-order calculations show significant deviations, demonstrating that higher-order perturbative QCD corrections are crucial for this process. The resummed predictions with parton showers additionally provide an excellent description of the low transverse-momentum regime of the diphoton system.
Publisher: American Physical Society (APS)
Date: 09-08-2022
Publisher: Optica Publishing Group
Date: 2020
DOI: 10.1364/CLEO_AT.2020.AM2I.1
Abstract: We propose a raster scanning adaptive optics method that uses digital image segmentation and a low-resolution deformable mirror with a maximum of 50 wavefront masks, which removes spatially varying aberrations (both s le and lens) across a field of view of 0.8 mm at 500 ms.
Publisher: American Physical Society (APS)
Date: 04-08-2022
Publisher: American Physical Society (APS)
Date: 08-08-2023
Publisher: American Physical Society (APS)
Date: 09-08-2022
Publisher: Elsevier BV
Date: 11-2016
Publisher: Elsevier BV
Date: 11-2016
Publisher: European Respiratory Society (ERS)
Date: 28-08-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0LC00598C
Abstract: Sub-micrometer lightsheet imaging of live fibroblast cell in PDMS microdevices by m-iSPIM.
Publisher: Wiley
Date: 17-01-2021
DOI: 10.1111/RESP.14003
Abstract: COVID‐19 is complicated by acute lung injury, and death in some in iduals. It is caused by SARS‐CoV‐2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. We obtained lower AEC from 145 people from two independent cohorts, aged 2–89 years, Newcastle ( n = 115) and Perth ( n = 30), Australia. The Newcastle cohort was enriched with people with asthma ( n = 37) and COPD ( n = 38). Gene expression for ACE2 and other genes potentially associated with SARS‐CoV‐2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Increased gene expression of ACE2 was associated with older age ( P = 0.03) and male sex ( P = 0.03), but not with pack‐years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients ( P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma ( P = 0.02), while ADAM‐17, a disintegrin that cleaves ACE2 from the surface, was increased ( P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over‐represented in those with COVID‐19 complications.
Publisher: AIP Publishing
Date: 08-2022
DOI: 10.1063/5.0091615
Abstract: Single-objective scanning light sheet (SOLS) imaging has fueled major advances in volumetric bioimaging because it supports low phototoxic, high-resolution imaging over an extended period. The remote imaging unit in the SOLS does not use a conventional epifluorescence image detection scheme (a single tube lens). In this paper, we propose a technique called the computational SOLS (cSOLS) that achieves light sheet imaging without the remote imaging unit. Using a single microlens array after the tube lens (lightfield imaging), the cSOLS is immediately compatible with conventional epifluorescence detection. The core of cSOLS is a Fast Optical Ray (FOR) model. FOR generates 3D imaging volume (40 × 40 × 14 µm3) using 2D lightfield images taken under SOLS illumination within 0.5 s on a standard central processing unit (CPU) without multicore parallel processing. In comparison with traditional lightfield retrieval approaches, FOR reassigns fluorescence photons and removes out-of-focus light to improve optical sectioning by a factor of 2, thereby achieving a spatial resolution of 1.59 × 1.92 × 1.39 µm3. cSOLS with FOR can be tuned over a range of oblique illumination angles and directions and, therefore, paves the way for next-generation SOLS imaging. cSOLS marks an important and exciting development of SOLS imaging with computational imaging capabilities.
Publisher: American Physiological Society
Date: 10-2020
DOI: 10.1152/AJPLUNG.00160.2020
Abstract: In 2019, the United States experienced the emergence of the vaping-associated lung injury (VALI) epidemic. Vaping is now known to result in the development and progression of severe lung disease in the young and healthy. Lack of regulation on electronic cigarettes in the United States has resulted in over 2,000 patients and 68 deaths. We examine the clinical representation of VALI and the delve into the scientific evidence of how deadly exposure to electronic cigarettes can be. E-cigarette vapor is shown to affect numerous cellular processes, cellular metabolism, and cause DNA damage (which has implications for cancer). E-cigarette use is associated with a higher risk of developing crippling lung conditions such as chronic obstructive pulmonary disease (COPD), which would develop several years from now, increasing the already existent smoking-related burden. The role of vaping and virus susceptibility is yet to be determined however, vaping can increase the virulence and inflammatory potential of several lung pathogens and is also linked to an increased risk of pneumonia. As it has emerged for cigarette smoking, great caution should also be given to vaping in relation to SARS-CoV-2 infection and the COVID-19 pandemic. Sadly, e-cigarettes are continually promoted and perceived as a safer alternative to cigarette smoking. E-cigarettes and their modifiable nature are harmful, as the lungs are not designed for the chronic inhalation of e-cigarette vapor. It is of interest that e-cigarettes have been shown to be of no help with smoking cessation. A true danger lies in vaping, which, if ignored, will lead to disastrous future costs.
Publisher: Informa UK Limited
Date: 19-06-2018
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JPBA.2016.08.013
Abstract: The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is formed from nicotine and related compounds during tobacco curing and is classified as a human carcinogen. Its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), is thought to be useful in the assessment of cigarette smoking harm minimisation strategies. Urine s les were collected from 24 current Caucasian smokers participating in a smoking cessation study before and four weeks after a quit attempt. S les were spiked with NNAL-d Free NNAL levels (193.5±158.2pg/mL [mean±standard deviation]) measured in urine s les obtained at baseline (during ad lib smoking) were indicative of biological exposure to NNK. Free NNAL levels were significantly reduced four weeks after the quit attempt (64.5±77.6pg/mL p<0.002). Assay performance met acceptance criteria with mean recovery of 59±23%, intra-day accuracy was 3.7%, 3.7 and 3.6% and precision was 11.3%, 5.1% and 5.3% at 5pg/mL, 20pg/mL and 100pg/mL levels respectively. Enzymatic hydrolysis of NNAL-glucuronide proved unreliable with complete loss of NNAL aglycone in some subject s les following the hydrolysis procedure. Liquid-liquid extraction with UPLC-MS/MS is a convenient approach to measure low levels of NNAL in urine as a marker of biological NNK exposure, which can be used to assess the effectiveness of smoking reduction harm minimisation strategies. Enzymatic hydrolysis of NNAL-glucuronide and measuring the aglycone is not recommended.
Publisher: American Physical Society (APS)
Date: 11-01-2022
Publisher: Springer Science and Business Media LLC
Date: 13-06-2022
Abstract: Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb − 1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at $$ \\sqrt{s} $$ s = 13 TeV is measured to be σ = 1 . 267 ± 0 . 005 ± 0 . 053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4 . 2%. The cross-section is measured differentially as a function of variables characterising the $$ t\\overline{t} $$ t t ¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators O tG and $$ {O}_{tq}^{(8)} $$ O tq 8 , where the limits on the latter are the most stringent to date.
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Physical Society (APS)
Date: 07-01-2022
Publisher: Springer Science and Business Media LLC
Date: 24-03-2017
DOI: 10.1007/S00213-017-4604-Y
Abstract: In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation outcomes. The objective of the current study was to test the effects of the pre-quit use of varenicline and nicotine patch on smoking rate and satisfaction with smoking. All participants were required to attend up to five study visit sections. Participants (n = 213) who were interested in quitting were randomised (open-label) to receive either pre-quit patch or varenicline (both treatments started 2 weeks prior to an assigned quit day, followed by 10 weeks post-quit) or standard patch (10 weeks starting from an assigned quit day). Participants used modified smartphones to monitor their smoking in real time for 4 weeks. Participants in the two pre-quit treatment groups reported significant reductions in both their satisfaction with smoking (p < 0.001) and smoking rate (p < 0.001) from baseline to the end of pre-quit period participants in the standard patch group did not. The observed reduction of smoking rate was associated with the satisfaction with smoking (p < 0.01), although the mediation effect of satisfaction was small. Pre-quit treatment caused reductions in satisfaction with smoking and smoking rate. Satisfaction was associated with changes in smoking rate, but the relationship was weak. As such, monitoring reductions in satisfaction do not appear to be a viable method of evaluating responsiveness to treatment.
Publisher: Springer Science and Business Media LLC
Date: 04-07-2022
DOI: 10.1038/S41586-022-04893-W
Abstract: The standard model of particle physics 1–4 describes the known fundamental particles and forces that make up our Universe, with the exception of gravity. One of the central features of the standard model is a field that permeates all of space and interacts with fundamental particles 5–9 . The quantum excitation of this field, known as the Higgs field, manifests itself as the Higgs boson, the only fundamental particle with no spin. In 2012, a particle with properties consistent with the Higgs boson of the standard model was observed by the ATLAS and CMS experiments at the Large Hadron Collider at CERN 10,11 . Since then, more than 30 times as many Higgs bosons have been recorded by the ATLAS experiment, enabling much more precise measurements and new tests of the theory. Here, on the basis of this larger dataset, we combine an unprecedented number of production and decay processes of the Higgs boson to scrutinize its interactions with elementary particles. Interactions with gluons, photons, and W and Z bosons—the carriers of the strong, electromagnetic and weak forces—are studied in detail. Interactions with three third-generation matter particles (bottom ( b ) and top ( t ) quarks, and tau leptons ( τ )) are well measured and indications of interactions with a second-generation particle (muons, μ ) are emerging. These tests reveal that the Higgs boson discovered ten years ago is remarkably consistent with the predictions of the theory and provide stringent constraints on many models of new phenomena beyond the standard model.
Publisher: Cold Spring Harbor Laboratory
Date: 22-07-2022
DOI: 10.1101/2022.07.22.501104
Abstract: To determine the molecular and/or mechanical basis of cell migration using live cell imaging tools, it is necessary to correlate multiple 3D spatiotemporal events simultaneously. Fluorescence nanoscopy and label free nanoscale imaging can complement each other by providing both molecular specificity and structural dynamics of sub-cellular structure. In doing so, a combined imaging system would permit quantitative 3D spatial temporal detail of in idual cellular components. In this paper, we empirically determined a series of optimal azimuthal scanning angles and rotating beam to achieve simultaneous and label-free nanoscale and fluorescence imaging. Label-free nanoscale imaging here refers to interferometric, brightfield (BF) and darkfield (DF) rotating coherence scattering (ROCS) microscopy, while fluorescence refers to high inclined Laminated Oblique (HiLO) and total internal reflection fluorescence (TIRF) imaging. The combined capabilities of interferometric, scattering and fluorescence imaging enables (1) the identification of molecular targets (substrate or organelle), (2) quantification of 3D cell morphodynamics, and (3) tracking of intracellular organelles in 3D. This combined imaging tool was then used to characterize migrating platelets and adherent endothelial cells, both critical to the process of infection and wound healing. The combined imaging results of over ∼1000 platelets, suggested that serum albumin (bovine) was necessary for platelets to migrate and scavenge fibrin/fibrinogen. Furthermore, we determine new asynchronous membrane fluctuations between the leading and rear edge of a migrating platelet. We further demonstrated that interferometric imaging permitted the quantification of mitochondria dynamics on lung microvascular cells (HMVEC). Our data suggests that axial displacement of mitochondria is minimized when it is closer to the nucleus or the leading edge of a cell membrane that exhibits retrograde motion. Taken together, this combined imaging platform has proven to quantify multiple spatial temporal events of a migrating cell, that will undoubtedly open ways to new quantitative correlative nanoscale live cell imaging.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2022
DOI: 10.1007/S41781-021-00062-2
Abstract: The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of s ling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are pres led, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such pres led event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
Publisher: Cold Spring Harbor Laboratory
Date: 20-08-2020
DOI: 10.1101/2020.08.17.254292
Abstract: Although existing microfluidics in vitro assays recapitulate blood vessel microenvironment using surface-immobilized agonists under biofluidic flows, these assays do not quantify intra-thrombus mass and activities of adhesive platelets at agonist margin and uses fluorescence labeling, therefore limiting clinical translation potential. Here, we describe a real time label-free in vitro quantitative imaging flow assay called C oherent O ptical S cattering and phase I nterferometry (COSI) that evaluates both intra-thrombus and adhesive-only platelet dynamics using only changes in refractive index. By combining coherent optical scattering and optical interferometry, we evaluated and quantified both intra-thrombus mass with picogram accuracy and adhesive platelet-only events/dynamics with high spatial-temporal resolution (400 nm/s) under fluid shear stress using only changes in refractive index. Using oblique illumination, COSI provide a ∼ 4 µm thin axial slice that quantifies the magnitude of physical of surface adhesive platelets (spreading, adhesion and consolidation) in a developing thrombus without labelling under fluid shear stress. We achieve real time visualization of recruitment of single platelet into thrombus and further correlate it to the developing mass of a thrombus. The adhesive platelet activity exhibit stabilized surface activity of around 2 µm/s and intra-thrombus mass exchange were balanced at around 1 picogram after treatment of a broad range metalloproteinase inhibitor (250 µM GM6001). The combination of phase imaging with transmitted light and backscattering imaging via oblique illumination in COSI unpicked intra-thrombus mass and adhesive platelet-only activity events at picogram and sub-micrometer precision with millisecond time resolution under fluid shear stress. COSI maps the longitudinal time dynamics of adhesive platelets along changing thrombus mass under metalloproteinase inhibition, and demonstrates potential for real-time correlative microfluidic label-free imaging for flow-dependent biological adhesive events.
Publisher: MDPI AG
Date: 15-11-2019
DOI: 10.3390/JCM8111986
Abstract: microRNAs (miRNAs) bind to mRNAs and inhibit their expression through post-transcriptionally regulating gene expression. Here, we elaborate upon the concise summary of the role of miRNAs in carcinogenesis with specific attention to precursor respiratory pathogenesis caused by cigarette smoke modulation of these miRNAs. We review how miRNAs are implicated in cigarette-smoke-driven mechanisms, such as epithelial to mesenchymal transition, autophagy modulation, and lung ageing, which are important in the development of chronic obstructive pulmonary disease and potential progression to lung cancer. Extracellular vesicles are key to inter-cellular communication and sharing of miRNAs. A deeper understanding of the role of miRNAs in chronic respiratory disease and their use as clinical biomarkers has great potential. Therapeutic targeting of miRNAs may significantly benefit the prevention of cancer progression.
Publisher: European Respiratory Society (ERS)
Date: 10-2022
DOI: 10.1183/23120541.00254-2022
Abstract: Pulmonary vascular remodelling in chronic obstructive pulmonary disease (COPD) has detrimental consequences for lung physiology. The aim of our study was to provide a comprehensive size-based morphometric quantification of pulmonary arterial remodelling in smokers and in patients with small airway disease (SAD) or COPD. Movat's pentachrome staining was performed on lung resections for 46 subjects: 12 never-smoker normal controls (NC), six normal lung function smokers (NLFS), nine patients with SAD, nine patients with mild-to-moderate COPD who were current smokers (COPD-CS) and 10 patients with mild-to-moderate COPD who were ex-smokers (COPD-ES). Following a size-based classification of pulmonary arteries, image analysis software was used to measure their number, total wall thickness, in idual layer thickness and elastin percentage. All pathological groups showed decreased numbers of pulmonary arteries compared with the NC group in all artery sizes. Arterial wall thickness was greater in NLFS and COPD-CS than in NC. Thickness in COPD-ES was decreased compared with COPD-CS. Intimal thickness was greater in all pathological groups in all arterial sizes than in the NC group. Medial thickness was also greater in small and medium arteries. Intimal thickness of larger arteries in COPD-CS correlated negatively to forced expiratory volume in 1 s/forced vital capacity (FVC) % and forced expiratory flow at 25–75% of FVC. Elastin deposition in small arteries was greatest in COPD-CS. Intimal elastin deposition had a more negative correlation with intimal thickness in NLFS and SAD than in COPD-CS. Smoking, SAD and mild-to-moderate COPD are associated with pruning and a decrease in the number of pulmonary arteries, increased wall thickness and variable elastin deposition. These changes were associated with worse airway obstruction.
Publisher: Informa UK Limited
Date: 2022
DOI: 10.2147/COPD.S329783
Publisher: MDPI AG
Date: 09-10-2020
DOI: 10.3390/BIOMEDICINES8100402
Abstract: The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2022
Abstract: A study of $$ {B}_c^{+}\\to J/\\psi {D}_s^{+} $$ B c + → J / ψ D s + and $$ {B}_c^{+}\\to J/\\psi {D}_s^{\\ast +} $$ B c + → J / ψ D s ∗ + decays using 139 fb − 1 of integrated luminosity collected with the ATLAS detector from $$ \\sqrt{s} $$ s = 13 TeV pp collisions at the LHC is presented. The ratios of the branching fractions of the two decays to the branching fraction of the $$ {B}_c^{+} $$ B c + → J/ψπ + decay are measured: $$ \\mathcal{B}\\left({B}_c^{+}\\to J/\\psi {D}_s^{+}\\right)/\\mathcal{B}\\left({B}_c^{+}\\to J/{\\psi \\pi}^{+}\\right) $$ B B c + → J / ψ D s + / B B c + → J / ψπ + = 2 . 76 ± 0 . 47 and $$ \\mathcal{B}\\left({B}_c^{+}\\to J/\\psi {D}_s^{\\ast +}\\right)/\\mathcal{B}\\left({B}_c^{+}\\to J/{\\psi \\pi}^{+}\\right) $$ B B c + → J / ψ D s ∗ + / B B c + → J / ψπ + = 5 . 33 ± 0 . 96. The ratio of the branching fractions of the two decays is found to be $$ \\mathcal{B}\\left({B}_c^{+}\\to J/\\psi {D}_s^{\\ast +}\\right)/\\mathcal{B}\\left({B}_c^{+}\\to J/\\psi {D}_s^{\\ast +}\\right) $$ B B c + → J / ψ D s ∗ + / B B c + → J / ψ D s ∗ + = 1 . 93 ± 0 . 26. For the $$ {B}_c^{+}\\to J/\\psi {D}_s^{\\ast +} $$ B c + → J / ψ D s ∗ + decay, the transverse polarization fraction, Γ ±± / Γ, is measured to be 0 . 70 ± 0 . 11. The reported uncertainties include both the statistical and systematic components added in quadrature. The precision of the measurements exceeds that in all previous studies of these decays. These results supersede those obtained in the earlier ATLAS study of the same decays with $$ \\sqrt{s} $$ s = 7 and 8 TeV pp collision data. A comparison with available theoretical predictions for the measured quantities is presented.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2022
Abstract: This paper presents updated Monte Carlo configurations used to model the production of single electroweak vector bosons ( W , Z/γ ∗ ) in association with jets in proton-proton collisions for the ATLAS experiment at the Large Hadron Collider. Improvements pertaining to the electroweak input scheme, parton-shower splitting kernels and scale-setting scheme are shown for multi-jet merged configurations accurate to next-to-leading order in the strong and electroweak couplings. The computational resources required for these set-ups are assessed, and approximations are introduced resulting in a factor three reduction of the per-event CPU time without affecting the physics modelling performance. Continuous statistical enhancement techniques are introduced by ATLAS in order to populate low cross-section regions of phase space and are shown to match or exceed the generated effective luminosity. This, together with the lower per-event CPU time, results in a 50% reduction in the required computing resources compared to a legacy set-up previously used by the ATLAS collaboration. The set-ups described in this paper will be used for future ATLAS analyses and lay the foundation for the next generation of Monte Carlo predictions for single vector-boson plus jets production.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1140/EPJC/S10052-022-10785-0
Abstract: A search for the pair production of heavy leptons as predicted by the type-III seesaw mechanism is presented. The search uses proton–proton collision data at a centre-of-mass energy of 13 TeV, corresponding to $$139\\,\\text {fb}^{-1}$$ 139 fb - 1 of integrated luminosity recorded by the ATLAS detector during Run 2 of the Large Hadron Collider. The analysis focuses on final states with three or four electrons or muons from the possible decays of new heavy leptons via intermediate electroweak bosons. No significant deviations above the Standard Model expectation are observed upper and lower limits on the heavy lepton production cross-section and masses are derived respectively. These results are then combined for the first time with the ones already published by ATLAS using the channel with two leptons in the final state. The observed lower limit on the mass of the type-III seesaw heavy leptons combining two, three and four lepton channels together is 910 GeV at the 95% confidence level.
Publisher: Elsevier BV
Date: 2022
Publisher: European Respiratory Society (ERS)
Date: 16-02-2023
DOI: 10.1183/23120541.00487-2022
Abstract: We have previously reported arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and suggested that endothelial-to-mesenchymal transition (EndMT) might be central to these changes. This study aims to provide evidence for active EndMT in IPF patients. Lung resections from 13 patients with IPF and 15 normal controls (NCs) were immunostained for EndMT biomarkers: vascular endothelial cadherin (VE-cadherin), neural cadherin (N-cadherin), S100A4 and vimentin. Pulmonary arteries were analysed for EndMT markers by using computer- and microscope-assisted image analysis software Image ProPlus7.0. All the analysis was done with observer blinded to subject and diagnosis. Increased expression of mesenchymal markers N-cadherin (p .0001), vimentin (p .0001) and S100A4 (p .05) was noted with downregulation of junctional endothelial VE-cadherin (p .01) in the intimal layer of the arteries from patients with IPF compared to NCs. Cadherin switch was observed in IPF patients, showing increase in endothelial N-cadherin and decrease in VE-cadherin (p .01). There was also VE-cadherin shift from junctions to cytoplasm (p .01), effecting endothelial cell integrity in patients with IPF. In IPF, in idual mesenchymal markers vimentin and N-cadherin negatively correlated with diffusing capacity of the lungs for carbon monoxide (r′= −0.63, p=0.03 and r′= −0.66, p=0.01). Further, N-cadherin positively correlated with arterial thickness (r′=0.58, p=0.03). This is the first study to demonstrate active EndMT in size-based classified pulmonary arteries from IPF patients and potential role in driving remodelling changes. The mesenchymal markers had a negative impact on the diffusing capacity of the lungs for carbon monoxide. This work also informs early origins of pulmonary hypertension in patients with IPF.
Publisher: American Chemical Society (ACS)
Date: 14-11-2022
Publisher: MDPI AG
Date: 03-03-2021
DOI: 10.3390/JCM10051028
Abstract: Tobacco smoking has emerged as a risk factor for increasing the susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via increased expression of angiotensin-converting enzyme-2 (ACE2) in the lung, linked to coronavirus disease 2019 (COVID-19) development. Given the modifiable nature of electronic cigarettes and the delivery of high concentrations of nicotine, we investigate whether electronic cigarette vaping has the potential to increase susceptibility to SARS-CoV-2 infection. We exposed BEAS-2B cells (bronchial epithelium transformed with Ad12-SV40 2B) and primary small airway epithelial cells (SAECs) to electronic cigarette aerosol condensates produced from propylene glycol/vegetable glycerin or commercially bought e-liquid (±added nicotine) and cigarette smoke extract to investigate if electronic cigarette exposure, like cigarette smoke, increases the expression of ACE2 in lung epithelial cells. In BEAS-2B cells, cytotoxicity (CCK-8), membrane integrity (LDH), and ACE2 protein expression (immunofluorescence) were measured for both 4- and 24 h treatments in BEAS-2B cells and 4 h in SAECs ACE2 gene expression was measured using quantitative polymerase chain reaction (qPCR) for 4 h treatment in BEAS-2B cells. Nicotine-free condensates and higher concentrations of nicotine-containing condensates were cytotoxic to BEAS-2B cells. Higher LDH release and reduced membrane integrity were seen in BEAS-2B cells treated for 24 h with higher concentrations of nicotine-containing condensates. ACE2 protein expression was observably increased in all treatments compared to cell controls, particularly for 24 h exposures. ACE2 gene expression was significantly increased in cells exposed to the locally bought e-liquid condensate with high nicotine concentration and cigarette smoke extract compared with cell controls. Our study suggests that vaping alone and smoking alone can result in an increase in lung ACE2 expression. Vaping and smoking are avoidable risk factors for COVID-19, which, if avoided, could help reduce the number of COVID-19 cases and the severity of the disease. This is the first study to utilize electronic cigarette aerosol condensates, novel and developed in our laboratory, for investigating ACE2 expression in human airway epithelial cells.
Publisher: MDPI AG
Date: 06-07-2020
DOI: 10.20944/PREPRINTS202007.0097.V1
Abstract: The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticular stress (ER stress). Since GPCR signalling is pivotal in numerous malignant pathologies, they are targeted by a number of clinically used drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.
Publisher: Informa UK Limited
Date: 15-06-2015
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1038/S41374-018-0146-0
Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation. Small airway fibrosis and obliteration are known to cause fixed airflow obstruction in COPD, and the consequential damage to the lung has an early onset. So far, there is little evidence of the mechanisms that underlie this aspect of pathology. However, emerging research confirms that airway epithelial reprogramming or epithelial to mesenchymal transition (EMT) is a key mechanism that drives fibrotic remodelling changes in smokers and patients with COPD. A recent study by Lai et al. further highlights the importance of EMT in smoking-related COPD pathology. The authors identify HB-EGF, an EGFR ligand, as a key driver of EMT and a potential new therapeutic target for the amelioration of EMT and airway remodelling. There are also wider implications in lung cancer prophylaxis, which is another major comorbidity associated with COPD. We consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2022
DOI: 10.1140/EPJC/S10052-022-10588-3
Abstract: A search for the Higgs boson decaying into a pair of charm quarks is presented. The analysis uses proton–proton collisions to target the production of a Higgs boson in association with a leptonically decaying W or Z boson. The dataset delivered by the LHC at a centre-of-mass energy of "Equation missing" and recorded by the ATLAS detector corresponds to an integrated luminosity of 139 $$\text{ fb}^{-1}$$ fb - 1 . Flavour-tagging algorithms are used to identify jets originating from the hadronisation of charm quarks. The analysis method is validated with the simultaneous measurement of WW , WZ and ZZ production, with observed (expected) significances of 2.6 (2.2) standard deviations above the background-only prediction for the $$(W/Z)Z(\rightarrow c{\bar{c}})$$ ( W / Z ) Z ( → c c ¯ ) process and 3.8 (4.6) standard deviations for the $$(W/Z)W(\rightarrow cq)$$ ( W / Z ) W ( → c q ) process. The $$(W/Z)H(\rightarrow c {\bar{c}})$$ ( W / Z ) H ( → c c ¯ ) search yields an observed (expected) upper limit of 26 (31) times the predicted Standard Model cross-section times branching fraction for a Higgs boson with a mass of "Equation missing" , corresponding to an observed (expected) constraint on the charm Yukawa coupling modifier $$|\kappa _c| 8.5~(12.4)$$ | κ c | 8.5 ( 12.4 ) , at the 95% confidence level. A combination with the ATLAS $$(W/Z)H, H\rightarrow b{\bar{b}}$$ ( W / Z ) H , H → b b ¯ analysis is performed, allowing the ratio $$\kappa _c / \kappa _b$$ κ c / κ b to be constrained to less than 4.5 at the 95% confidence level, smaller than the ratio of the b- and c-quark masses, and therefore determines the Higgs-charm coupling to be weaker than the Higgs-bottom coupling at the 95% confidence level.
Publisher: Springer Science and Business Media LLC
Date: 06-2022
Abstract: A search for decays of pair-produced neutral long-lived particles (LLPs) is presented using 139 fb − 1 of proton-proton collision data collected by the ATLAS detector at the LHC in 2015–2018 at a centre-of-mass energy of 13 TeV. Dedicated techniques were developed for the reconstruction of displaced jets produced by LLPs decaying hadronically in the ATLAS hadronic calorimeter. Two search regions are defined for different LLP kinematic regimes. The observed numbers of events are consistent with the expected background, and limits for several benchmark signals are determined. For a SM Higgs boson with a mass of 125 GeV, branching ratios above 10% are excluded at 95% confidence level for values of c times LLP mean proper lifetime in the range between 20 mm and 10 m depending on the model. Upper limits are also set on the cross-section times branching ratio for scalars with a mass of 60 GeV and for masses between 200 GeV and 1 TeV.
Publisher: Springer Science and Business Media LLC
Date: 11-2021
Abstract: A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb − 1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b -hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be $$ {26}_{-15}^{+17} $$ 26 − 15 + 17 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be $$ {24}_{-6}^{+7} $$ 24 − 6 + 7 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12 . 0 ± 2 . 4 fb.
Publisher: MDPI AG
Date: 23-01-2021
Abstract: The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion’s instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.
Publisher: American Physiological Society
Date: 2021
DOI: 10.1152/AJPLUNG.00437.2020
Abstract: Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack. The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with COPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were never-smoking normal controls. Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using Image ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.
Publisher: American Physiological Society
Date: 10-2022
DOI: 10.1152/AJPLUNG.00137.2022
Abstract: Management of patients with asthma COPD overlap (ACO) is clinically challenging due to insufficient evidence of pathological changes in these patients. In this cross-sectional study, we evaluated airway remodeling in endobronchial biopsies from a total of 90 subjects, which included 12 ACO, 14 patients with asthma, 12 COPD exsmokers (ES), 11 current smokers (CS), 28 healthy controls (HC), and 13 normal lung function smokers (NLFS). Tissue was stained with Masson’s trichrome. Epithelium, goblet cells, reticular basement membrane (RBM), cellularity, lamina propria (LP), and smooth muscle (SM) changes were measured using Image-Pro Plus v7 software. Differential airway remodeling pattern was seen in patients with ACO. A limited change was noted in the ACO epithelium compared with other pathological groups. RBM was substantially thicker in patients with ACO than in HC ( P 0.0002) and tended to be thicker than in patients with asthma and NLFS. The total RBM cells were higher in ACO than in the HC ( P 0.0001), COPD-CS ( P = 0.0559), -ES ( P = 0.0345), and NLFS ( P 0.0002), but did not differ from patients with asthma. Goblet cells were higher in the ACO than in the HC ( P = 0.0028) and COPD-ES ( P = 0.0081). The total LP cells in ACO appeared to be higher than in HC, COPD-CS, and NLFS but appeared to be lower than in patients with asthma. Finally, SM area was significantly lower in the ACO than in patients with asthma ( P = 0.001), COPD-CS (=0.0290), and NLFS ( P = 0.0011). This first comprehensive study suggests that patients with ACO had distinguishable tissue remodeling that appeared to be more severe than patients with asthma and COPD. This study will help in informed decision-making for better patient management in clinical practice.
Publisher: Springer Science and Business Media LLC
Date: 03-2022
Abstract: Searches are conducted for new spin-0 or spin-1 bosons using events where a Higgs boson with mass 125 GeV decays into four leptons ( ℓ = e , μ ). This decay is presumed to occur via an intermediate state which contains two on-shell, promptly decaying bosons: H → XX/ZX → 4 ℓ , where the new boson X has a mass between 1 and 60 GeV. The search uses pp collision data collected with the ATLAS detector at the LHC with an integrated luminosity of 139 fb − 1 at a centre-of-mass energy $$ \\sqrt{s} $$ s = 13 TeV. The data are found to be consistent with Standard Model expectations. Limits are set on fiducial cross sections and on the branching ratio of the Higgs boson to decay into XX/ZX , improving those from previous publications by a factor between two and four. Limits are also set on mixing parameters relevant in extensions of the Standard Model containing a dark sector where X is interpreted to be a dark boson.
Publisher: SPIE
Date: 29-04-2017
DOI: 10.1117/12.2275706
Publisher: Optica Publishing Group
Date: 09-09-2020
DOI: 10.1364/BOE.395302
Abstract: Intensity shot noise in digital holograms distorts the quality of the phase images after phase retrieval, limiting the usefulness of quantitative phase microscopy (QPM) systems in long term live cell imaging. In this paper, we devise a hologram-to-hologram neural network, Holo-UNet, that restores high quality digital holograms under high shot noise conditions (sub-mW/cm 2 intensities) at high acquisition rates (sub-milliseconds). In comparison to current phase recovery methods, Holo-UNet denoises the recorded hologram, and so prevents shot noise from propagating through the phase retrieval step that in turn adversely affects phase and intensity images. Holo-UNet was tested on 2 independent QPM systems without any adjustment to the hardware setting. In both cases, Holo-UNet outperformed existing phase recovery and block-matching techniques by ∼ 1.8 folds in phase fidelity as measured by SSIM. Holo-UNet is immediately applicable to a wide range of other high-speed interferometric phase imaging techniques. The network paves the way towards the expansion of high-speed low light QPM biological imaging with minimal dependence on hardware constraints.
Publisher: AME Publishing Company
Date: 05-2019
Publisher: American Physical Society (APS)
Date: 07-06-2022
Publisher: Springer Science and Business Media LLC
Date: 09-11-2022
Abstract: A simultaneous measurement of the three components of the top-quark and top-antiquark polarisation vectors in t -channel single-top-quark production is presented. This analysis is based on data from proton–proton collisions at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 139 fb − 1 , collected with the ATLAS detector at the LHC. Selected events contain exactly one isolated electron or muon, large missing transverse momentum and exactly two jets, one being b -tagged. Stringent selection requirements are applied to discriminate t -channel single-top-quark events from the background contributions. The top-quark and top-antiquark polarisation vectors are measured from the distributions of the direction cosines of the charged-lepton momentum in the top-quark rest frame. The three components of the polarisation vector for the selected top-quark event s le are $$ {P}_{x^{\\prime }} $$ P x ′ = 0 . 01 ± 0 . 18, $$ {P}_{y^{\\prime }} $$ P y ′ = − 0 . 029 ± 0 . 027, $$ {P}_{z^{\\prime }} $$ P z ′ = 0 . 91 ± 0 . 10 and for the top-antiquark event s le they are $$ {P}_{x^{\\prime }} $$ P x ′ = − 0 . 02 ± 0 . 20, $$ {P}_{y^{\\prime }} $$ P y ′ = − 0 . 007 ± 0 . 051, $$ {P}_{z^{\\prime }} $$ P z ′ = 0 . 79 ± 0 . 16. Normalised differential cross-sections corrected to a fiducial region at the stable-particle level are presented as a function of the charged-lepton angles for top-quark and top-antiquark events inclusively and separately. These measurements are in agreement with Standard Model predictions. The angular differential cross-sections are used to derive bounds on the complex Wilson coefficient of the dimension-six $$ \\mathcal{O} $$ O tW operator in the framework of an effective field theory. The obtained bounds are C tW ∈ [ − 0 . 9 , 1 . 4] and C itW ∈ [ − 0 . 8 , 0 . 2], both at 95% confidence level.
Publisher: Springer Science and Business Media LLC
Date: 02-08-2022
Abstract: A measurement of inclusive and differential fiducial cross-sections for the production of the Higgs boson decaying into two photons is performed using 139 fb − 1 of proton-proton collision data recorded at $$ \\sqrt{s} $$ s = 13 TeV by the ATLAS experiment at the Large Hadron Collider. The inclusive cross-section times branching ratio, in a fiducial region closely matching the experimental selection, is measured to be 67 ± 6 fb, which is in agreement with the state-of-the-art Standard Model prediction of 64 ± 4 fb. Extrapolating this result to the full phase space and correcting for the branching ratio, the total cross-section for Higgs boson production is estimated to be 58 ± 6 pb. In addition, the cross-sections in four fiducial regions sensitive to various Higgs boson production modes and differential cross-sections as a function of either one or two of several observables are measured. All the measurements are found to be in agreement with the Standard Model predictions. The measured transverse momentum distribution of the Higgs boson is used as an indirect probe of the Yukawa coupling of the Higgs boson to the bottom and charm quarks. In addition, five differential cross-section measurements are used to constrain anomalous Higgs boson couplings to vector bosons in the Standard Model effective field theory framework.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
Abstract: The fragmentation properties of jets containing b -hadrons are studied using charged B mesons in 139 fb − 1 of pp collisions at $$ \\sqrt{s} $$ s = 13 TeV, recorded with the ATLAS detector at the LHC during the period from 2015 to 2018. The B mesons are reconstructed using the decay of B ± into J/ψK ± , with the J/ψ decaying into a pair of muons. Jets are reconstructed using the anti- k t algorithm with radius parameter R = 0 . 4. The measurement determines the longitudinal and transverse momentum profiles of the reconstructed B hadrons with respect to the axes of the jets to which they are geometrically associated. These distributions are measured in intervals of the jet transverse momentum, ranging from 50 GeV to above 100 GeV. The results are corrected for detector effects and compared with several Monte Carlo predictions using different parton shower and hadronisation models. The results for the longitudinal and transverse profiles provide useful inputs to improve the description of heavy-flavour fragmentation in jets.
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1140/EPJC/S10052-022-10101-W
Abstract: A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using $$139\\,{\\mathrm {fb}}^{-1}$$ 139 fb - 1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at $$\\sqrt{s}=13\\,\\text {TeV}$$ s = 13 TeV . The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic $$t{\\bar{t}}$$ t t ¯ decay channel, and the hadronically decaying top quark must have transverse momentum above $$350\\,\\text {GeV}$$ 350 GeV . The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be $$-0.043\\pm 0.020$$ - 0.043 ± 0.020 , in agreement with the SM prediction of $$-0.037\\pm 0.003$$ - 0.037 ± 0.003 . Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2022
DOI: 10.1140/EPJC/S10052-022-10366-1
Abstract: This article presents the results of two studies of Higgs boson properties using the $$WW^*(\\rightarrow e\\nu \\mu \\nu )jj$$ W W ∗ ( → e ν μ ν ) j j final state, based on a dataset corresponding to $${36.1}{{\\mathrm{fb}}^{-1}}$$ 36.1 fb - 1 of $$\\sqrt{s}=13$$ s = 13 TeV proton–proton collisions recorded by the ATLAS experiment at the Large Hadron Collider. The first study targets Higgs boson production via gluon–gluon fusion and constrains the CP properties of the effective Higgs–gluon interaction. Using angular distributions and the overall rate, a value of $$\\tan (\\alpha ) = 0.0 \\pm 0.4 (\\mathrm {stat.}) \\pm 0.3 (\\mathrm {syst.})$$ tan ( α ) = 0.0 ± 0.4 ( stat . ) ± 0.3 ( syst . ) is obtained for the tangent of the mixing angle for CP-even and CP-odd contributions. The second study exploits the vector-boson fusion production mechanism to probe the Higgs boson couplings to longitudinally and transversely polarised W and Z bosons in both the production and the decay of the Higgs boson these couplings have not been directly constrained previously. The polarisation-dependent coupling-strength scale factors are defined as the ratios of the measured polarisation-dependent coupling strengths to those predicted by the Standard Model, and are determined using rate and kinematic information to be $$a_\\mathrm {L}=0.91^{+0.10}_{-0.18}$$ a L = 0 . 91 - 0.18 + 0.10 (stat.) $$^{+0.09}_{-0.17}$$ - 0.17 + 0.09 (syst.) and $$a_{\\mathrm {T}}=1.2 \\pm 0.4 $$ a T = 1.2 ± 0.4 (stat.) $$ ^{+0.2}_{-0.3} $$ - 0.3 + 0.2 (syst.). These coupling strengths are translated into pseudo-observables, resulting in $$\\kappa _{VV}= 0.91^{+0.10}_{-0.18}$$ κ VV = 0 . 91 - 0.18 + 0.10 (stat.) $$^{+0.09}_{-0.17}$$ - 0.17 + 0.09 (syst.) and $$\\epsilon _{VV} =0.13^{+0.28}_{-0.20}$$ ϵ VV = 0 . 13 - 0.20 + 0.28 (stat.) $$^{+0.08}_{-0.10}$$ - 0.10 + 0.08 (syst.). All results are consistent with the Standard Model predictions.
Publisher: Optica Publishing Group
Date: 2020
DOI: 10.1364/MICROSCOPY.2020.MTH3A.3
Abstract: In this work, we propose a label-free COSI system to investigating morphological changes and platelet-platelet interactions within a thrombus during embolism events to interrogate prothrombotic events within a microfluidics channel under flow.
Publisher: Springer Science and Business Media LLC
Date: 17-06-2022
Abstract: The associated production of a Higgs boson and a top-quark pair is measured in events characterised by the presence of one or two electrons or muons. The Higgs boson decay into a b -quark pair is used. The analysed data, corresponding to an integrated luminosity of 139 fb − 1 , were collected in proton-proton collisions at the Large Hadron Collider between 2015 and 2018 at a centre-of-mass energy of $$ \\sqrt{s} $$ s = 13 TeV. The measured signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model, is $$ {0.35}_{-0.34}^{+0.36} $$ 0.35 − 0.34 + 0.36 . This result is compatible with the Standard Model prediction and corresponds to an observed (expected) significance of 1.0 (2.7) standard deviations. The signal strength is also measured differentially in bins of the Higgs boson transverse momentum in the simplified template cross-section framework, including a bin for specially selected boosted Higgs bosons with transverse momentum above 300 GeV.
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1140/EPJC/S10052-022-10182-7
Abstract: A search is presented for the production of a single top quark via left-handed flavour-changing neutral-current (FCNC) interactions of a top quark, a gluon and an up or charm quark. Two production processes are considered: $$u+g\rightarrow t$$ u + g → t and $$c+g\rightarrow t$$ c + g → t . The analysis is based on proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. The data set corresponds to an integrated luminosity of 139 fb $$^{-1}$$ - 1 . Events with exactly one electron or muon, exactly one b -tagged jet and missing transverse momentum are selected, resembling the decay products of a singly produced top quark. Neural networks based on kinematic variables differentiate between events from the two signal processes and events from background processes. The measured data are consistent with the background-only hypothesis, and limits are set on the production cross-sections of the signal processes: $$\sigma (u+g\rightarrow t)\times \mathcal {B}(t\rightarrow Wb)\times \mathcal {B}(W\rightarrow \ell \nu ) .0\,$$ σ ( u + g → t ) × B ( t → W b ) × B ( W → ℓ ν ) 3.0 pb and $$\sigma (c+g\rightarrow t)\times \mathcal {B}(t\rightarrow Wb)\times \mathcal {B}(W\rightarrow \ell \nu ) .7\,$$ σ ( c + g → t ) × B ( t → W b ) × B ( W → ℓ ν ) 4.7 pb at the 95% confidence level, with $$\mathcal {B}(W\rightarrow \ell \nu )=0.325$$ B ( W → ℓ ν ) = 0.325 being the sum of branching ratios of all three leptonic decay modes of the W boson. Based on the framework of an effective field theory, the cross-section limits are translated into limits on the strengths of the tug and tcg couplings occurring in the theory: $$|C^{\,ut}_{uG}|/\Lambda ^2 0.057\,$$ | C uG u t | / Λ 2 0.057 TeV $$^{-2}$$ - 2 and $$|C^{\,ct}_{uG}|/\Lambda ^2 0.14\,$$ | C uG c t | / Λ 2 0.14 TeV $$^{-2}$$ - 2 . These bounds correspond to limits on the branching ratios of FCNC-induced top-quark decays: $$\mathcal {B}(t\rightarrow u+g) 0.61\times 10^{-4}$$ B ( t → u + g ) 0.61 × 10 - 4 and $$\mathcal {B}(t\rightarrow c+g) 3.7\times 10^{-4}$$ B ( t → c + g ) 3.7 × 10 - 4 .
Publisher: European Respiratory Society (ERS)
Date: 07-2022
DOI: 10.1183/13993003.01431-2021
Abstract: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase (hCMA)1 and its orthologue mCMA1/mouse mast cell protease (mMCP)5 are exocytosed from activated mast cells and have adverse roles in numerous disorders, but their role in COPD is unknown. We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5 -deficient ( −/− ) mice to evaluate this protease's role and potential for therapeutic targeting in CS-induced experimental COPD. In addition, we used ex vivo/in vitro studies to define mechanisms. The levels of hCMA1 mRNA and CMA1 + mast cells were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated mast cell numbers and mMCP5 protein were increased in lung tissues of wild-type mice with experimental COPD. mmcp5 −/− mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of mast cells from wild-type, but not mmcp5 −/− mice with wild-type lung macrophages increased in tumour necrosis factor (TNF)-α release. It also caused the release of CMA1 from human mast cells, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD. CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2022
Abstract: Measurements of the production cross-sections of the Standard Model (SM) Higgs boson ( H ) decaying into a pair of τ -leptons are presented. The measurements use data collected with the ATLAS detector from pp collisions produced at the Large Hadron Collider at a centre-of-mass energy of $$ \sqrt{s} $$ s = 13 TeV, corresponding to an integrated luminosity of 139 fb − 1 . Leptonic ( τ → ℓν ℓ ν τ ) and hadronic ( τ → hadrons ν τ ) decays of the τ -lepton are considered. All measurements account for the branching ratio of H → ττ and are performed with a requirement |y H | 2 . 5, where y H is the true Higgs boson rapidity. The cross-section of the pp → H → ττ process is measured to be 2 . 94 ± $$ 0.21{\left(\mathrm{stat}\right)}_{-0.32}^{+0.37} $$ 0.21 stat − 0.32 + 0.37 (syst) pb, in agreement with the SM prediction of 3 . 17 ± 0 . 09 pb. Inclusive cross-sections are determined separately for the four dominant production modes: 2 . 65 ± $$ 0.41{\left(\mathrm{stat}\right)}_{-0.67}^{+0.91} $$ 0.41 stat − 0.67 + 0.91 (syst) pb for gluon-gluon fusion, 0 . 197 ± $$ 0.028{\left(\mathrm{stat}\right)}_{-0.026}^{+0.032} $$ 0.028 stat − 0.026 + 0.032 (syst) pb for vector-boson fusion, 0 . 115 ± $$ 0.058{\left(\mathrm{stat}\right)}_{-0.040}^{+0.042} $$ 0.058 stat − 0.040 + 0.042 (syst) pb for vector-boson associated production, and 0 . 033 ± $$ 0.031{\left(\mathrm{stat}\right)}_{-0.017}^{+0.022} $$ 0.031 stat − 0.017 + 0.022 (syst) pb for top-quark pair associated production. Measurements in exclusive regions of the phase space, using the simplified template cross-section framework, are also performed. All results are in agreement with the SM predictions.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2022
DOI: 10.1007/S41781-021-00079-7
Abstract: The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.
Publisher: Elsevier BV
Date: 10-2021
Publisher: European Respiratory Society (ERS)
Date: 07-2019
Publisher: American Physical Society (APS)
Date: 27-12-2021
Publisher: American Physical Society (APS)
Date: 25-08-2023
Publisher: Elsevier BV
Date: 08-2021
Publisher: Optica Publishing Group
Date: 2020
DOI: 10.1364/CLEO_AT.2020.AM1I.4
Abstract: In this work, we propose a label-free COSI system to quantify morphological changes and platelet activity along non-patterned collagen fibers within millisecond in microfluidics channels under flow at sub-platelet imaging resolution.
Publisher: American Physical Society (APS)
Date: 14-08-2023
Publisher: Springer Science and Business Media LLC
Date: 11-07-2022
DOI: 10.1140/EPJC/S10052-022-10472-0
Abstract: This paper presents studies of Bose–Einstein correlations (BEC) in proton–proton collisions at a centre-of-mass energy of 13 TeV, using data from the ATLAS detector at the CERN Large Hadron Collider. Data were collected in a special low-luminosity configuration with a minimum-bias trigger and a high-multiplicity track trigger, accumulating integrated luminosities of 151 $$\upmu $$ μ b $$^{-1}$$ - 1 and 8.4 nb $$^{-1}$$ - 1 , respectively. The BEC are measured for pairs of like-sign charged particles, each with $$|\eta | 2.5$$ | η | 2.5 , for two kinematic ranges: the first with particle $$p_{\mathrm {T}} 100$$ p T 100 MeV and the second with particle $$p_{\mathrm {T}} 500$$ p T 500 MeV. The BEC parameters, characterizing the source radius and particle correlation strength, are investigated as functions of charged-particle multiplicity (up to 300) and average transverse momentum of the pair (up to 1.5 GeV). The double-differential dependence on charged-particle multiplicity and average transverse momentum of the pair is also studied. The BEC radius is found to be independent of the charged-particle multiplicity for high charged-particle multiplicity (above 100), confirming a previous observation at lower energy. This saturation occurs independent of the transverse momentum of the pair.
Publisher: MDPI AG
Date: 20-03-2020
DOI: 10.3390/JCM9030841
Abstract: The epicenter of the original outbreak in China has high male smoking rates of around 50%, and early reported death rates have an emphasis on older males, therefore the likelihood of smokers being overrepresented in fatalities is high. In Iran, China, Italy, and South Korea, female smoking rates are much lower than males. Fewer females have contracted the virus. If this analysis is correct, then Indonesia would be expected to begin experiencing high rates of Covid-19 because its male smoking rate is over 60% (Tobacco Atlas). Smokers are vulnerable to respiratory viruses. Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. This could also be true for new electronic smoking devices such as electronic cigarettes and “heat-not-burn” IQOS devices. ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation. Data on smoking status should be collected on all identified cases of Covid-19.
Publisher: MDPI AG
Date: 31-01-2022
DOI: 10.3390/JCM11030777
Abstract: We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-β1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF (p 0.01) and LAM (p 0.001) patients, and in the alveolar areas of IPF (p 0.001) and LAM (p 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, p 0.05) and alveolar areas (r = 0.941, p 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-β1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF.
Publisher: European Respiratory Society (ERS)
Date: 26-03-2021
DOI: 10.1183/23120541.00876-2020
Abstract: Previous reports have shown epithelial–mesenchymal transition (EMT) as an active process that contributes to small airway fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate small airway myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients. Lung resections from nonsmoker controls, normal lung function smokers and COPD current and ex-smokers were stained with anti-human α-smooth muscle actin (SMA), collagen 1 and fibronectin. αSMA + cells were computed in reticular basement membrane (Rbm), lamina propria and adventitia and presented per mm of Rbm and mm 2 of lamina propria. Collagen-1 and fibronectin are presented as a percentage change from normal. All analyses including airway thickness were measured using Image-pro-plus 7.0. We found an increase in subepithelial lamina propria (especially) and adventitia thickness in all pathological groups compared to nonsmoker controls. Increases in αSMA + myofibroblasts were observed in subepithelial Rbm, lamina propria and adventitia in both the smoker and COPD groups compared to nonsmoker controls. Furthermore, the increase in the myofibroblast population in the lamina propria was strongly associated with decrease in lung function, lamina propria thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells. This is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.
Publisher: Frontiers Media SA
Date: 03-11-2021
DOI: 10.3389/FMOLB.2021.780284
Abstract: Serum and glucocorticoid-regulated kinase 1 (SGK1) is a Ser/Thr protein kinase involved in regulating cell survival, growth, proliferation, and migration. Its elevated expression and dysfunction are reported in breast, prostate, hepatocellular, lung adenoma, and renal carcinomas. We have analyzed the SGK1 mutations to explore their impact at the sequence and structure level by utilizing state-of-the-art computational approaches. Several pathogenic and destabilizing mutations were identified based on their impact on SGK1 and analyzed in detail. Three amino acid substitutions, K127M, T256A, and Y298A, in the kinase domain of SGK1 were identified and incorporated structurally into original coordinates of SGK1 to explore their time evolution impact using all-atom molecular dynamic (MD) simulations for 200 ns. MD results indicate substantial conformational alterations in SGK1, thus its functional loss, particularly upon T256A mutation. This study provides meaningful insights into SGK1 dysfunction upon mutation, leading to disease progression, including cancer, and neurodegeneration.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Optica Publishing Group
Date: 23-01-2020
DOI: 10.1364/BOE.377044
Abstract: Removal of complex aberrations at millisecond time scales over millimeters in distance in multiphoton laser scanning microscopy limits the total spatiotemporal imaging throughput for deep tissue imaging. Using a single low resolution deformable mirror and time multiplexing (TM) adaptive optics, we demonstrate video rate aberration correction (5 ms update rate for a single wavefront mask) for a complex heterogeneous distribution of refractive index differences through a depth of up to 1.1 mm and an extended imaging FOV of up to 0.8 mm, with up to 167% recovery of fluorescence intensity 335 µm from the center of the FOV. The proposed approach, termed raster adaptive optics (RAO), integrates image-based aberration retrieval and video rate removal of arbitrarily defined regions of dominant, spatially varied wavefronts. The extended FOV was achieved by demonstrating rapid recovery of up to 50 distinct wavefront masks at 500 ms update rates that increased imaging throughput by 2.3-fold. Because RAO only requires a single deformable mirror with image-based aberration retrieval, it can be directly implemented on a standard laser scanning multiphoton microscope.
Publisher: Elsevier BV
Date: 06-2022
Publisher: European Respiratory Society (ERS)
Date: 19-05-2020
No related grants have been discovered for Wenying Lu.