83 research outputs found

    Recent Advancements in Fractal Geometric-Based Nonlinear Time Series Solutions to the Micro-Quasistatic Thermoviscoelastic Creep for Rough Surfaces in Contact

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    To understand the tripological contact phenomena, both mathematical and experimental models are needed. In this work, fractal mathematical models are used to model the experimental results obtained from literature. Fractal geometry, using a deterministic Cantor structure, is used to model the surface topography, where recent advancements in thermoviscoelastic creep contact of rough surfaces are introduced. Various viscoelastic idealizations are used to model the surface materials, for example, Maxwell, Kelvin-Voigt, Standard Linear Solid and Jeffrey media. Such media are modelled as arrangements of elastic springs and viscous dashpots in parallel and/or in series. Asymptotic power laws, through hypergeometric series, were used to express the surface creep as a function of remote forces, body temperatures and time. The introduced models are valid only when the creep approach of the contact surfaces is in the order of the size of the surface roughness. The obtained results using such models, which admit closed-form solutions, are displayed graphically for selected values of the systems' parameters; the fractal surface roughness and various material properties. Results obtained showed good agreement with published experimental results, where the utilized methodology can be further extended to the utilization for the contact of surfaces within micro- and nano-electronic devices, circuits and systems

    Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling

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    In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo

    Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

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    peer reviewed[en] BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease

    Carcinoma Matrix Controls Resistance to Cisplatin through Talin Regulation of NF-kB

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    Extracellular matrix factors within the tumor microenvironment that control resistance to chemotherapeutics are poorly understood. This study focused on understanding matrix adhesion pathways that control the oral carcinoma response to cisplatin. Our studies revealed that adhesion of HN12 and JHU012 oral carcinomas to carcinoma matrix supported tumor cell proliferation in response to treatment with cisplatin. Proliferation in response to 30 µM cisplatin was not observed in HN12 cells adherent to other purified extracellular matrices such as Matrigel, collagen I, fibronectin or laminin I. Integrin β1 was important for adhesion to carcinoma matrix to trigger proliferation after treatment with cisplatin. Disruption of talin expression in HN12 cells adherent to carcinoma matrix increased cisplatin induced proliferation. Pharmacological inhibitors were used to determine signaling events required for talin deficiency to regulate cisplatin induced proliferation. Pharmacological inhibition of NF-kB reduced proliferation of talin-deficient HN12 cells treated with 30 µM cisplatin. Nuclear NF-kB activity was assayed in HN12 cells using a luciferase reporter of NF-kB transcriptional activity. Nuclear NF-kB activity was similar in HN12 cells adherent to carcinoma matrix and collagen I when treated with vehicle DMSO. Following treatment with 30 µM cisplatin, NF-kB activity is maintained in cells adherent to carcinoma matrix whereas NF-kB activity is reduced in collagen I adherent cells. Expression of talin was sufficient to trigger proliferation of HN12 cells adherent to collagen I following treatment with 1 and 30 µM cisplatin. Talin overexpression was sufficient to trigger NF-kB activity following treatment with cisplatin in carcinoma matrix adherent HN12 cells in a process disrupted by FAK siRNA. Thus, adhesions within the carcinoma matrix create a matrix environment in which exposure to cisplatin induces proliferation through the function of integrin β1, talin and FAK pathways that regulate NF-kB nuclear activity

    Triple-GEM discharge probability studies at CHARM: Simulations and experimental results

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    The CMS muon system in the region with 2.03<|η|<2.82 is characterized by a very harsh radiation environment which can generate hit rates up to 144 kHz/cm2^{2} and an integrated charge of 8 C/cm2^{2} over ten years of operation. In order to increase the detector performance and acceptance for physics events including muons, a new muon station (ME0) has been proposed for installation in that region. The technology proposed is Triple—Gas Electron Multiplier (Triple-GEM), which has already been qualified for the operation in the CMS muon system. However, an additional set of studies focused on the discharge probability is necessary for the ME0 station, because of the large radiation environment mentioned above. A test was carried out in 2017 at the Cern High energy AcceleRator Mixed (CHARM) facility, with the aim of giving an estimation of the discharge probability of Triple-GEM detectors in a very intense radiation field environment, similar to the one of the CMS muon system. A dedicated standalone Geant4 simulation was performed simultaneously, to evaluate the behavior expected in the detector exposed to the CHARM field. The geometry of the detector has been carefully reproduced, as well as the background field present in the facility. This paper presents the results obtained from the Geant4 simulation, in terms of sensitivity of the detector to the CHARM environment, together with the analysis of the energy deposited in the gaps and of the processes developed inside the detector. The discharge probability test performed at CHARM will be presented, with a complete discussion of the results obtained, which turn out to be consistent with measurements performed by other groups

    Benchmarking LHC background particle simulation with the CMS triple-GEM detector

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    In 2018, a system of large-size triple-GEM demonstrator chambers was installed in the CMS experiment at CERN\u27s Large Hadron Collider (LHC). The demonstrator\u27s design mimicks that of the final detector, installed for Run-3. A successful Monte Carlo (MC) simulation of the collision-induced background hit rate in this system in proton-proton collisions at 13 TeV is presented. The MC predictions are compared to CMS measurements recorded at an instantaneous luminosity of 1.5 ×1034^{34} cm2^{-2} s1^{-1}. The simulation framework uses a combination of the FLUKA and GEANT4 packages. FLUKA simulates the radiation environment around the GE1/1 chambers. The particle flux by FLUKA covers energy spectra ranging from 1011^{-11} to 104^{4} MeV for neutrons, 103^{-3} to 104^{4} MeV for γ\u27s, 102^{-2} to 104^{4} MeV for e±^{±}, and 101^{-1} to 104^{4} MeV for charged hadrons. GEANT4 provides an estimate of the detector response (sensitivity) based on an accurate description of the detector geometry, the material composition, and the interaction of particles with the detector layers. The detector hit rate, as obtained from the simulation using FLUKA and GEANT4, is estimated as a function of the perpendicular distance from the beam line and agrees with data within the assigned uncertainties in the range 13.7-14.5%. This simulation framework can be used to obtain a reliable estimate of the background rates expected at the High Luminosity LHC

    Modeling the triple-GEM detector response to background particles for the CMS Experiment

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    An estimate of environmental background hit rate on triple-GEM chambers is performed using Monte Carlo (MC) simulation and compared to data taken by test chambers installed in the CMS experiment (GE1/1) during Run-2 at the Large Hadron Collider (LHC). The hit rate is measured using data collected with proton-proton collisions at 13 TeV and a luminosity of 1.5×1034\times10^{34} cm2^{-2} s1^{-1}. The simulation framework uses a combination of the FLUKA and Geant4 packages to obtain the hit rate. FLUKA provides the radiation environment around the GE1/1 chambers, which is comprised of the particle flux with momentum direction and energy spectra ranging from 101110^{-11} to 10410^{4} MeV for neutrons, 10310^{-3} to 10410^{4} MeV for γ\gamma's, 10210^{-2} to 10410^{4} MeV for e±e^{\pm}, and 10110^{-1} to 10410^{4} MeV for charged hadrons. Geant4 provides an estimate of detector response (sensitivity) based on an accurate description of detector geometry, material composition and interaction of particles with the various detector layers. The MC simulated hit rate is estimated as a function of the perpendicular distance from the beam line and agrees with data within the assigned uncertainties of 10-14.5%. This simulation framework can be used to obtain a reliable estimate of background rates expected at the High Luminosity LHC.Comment: 16 pages, 9 figures, 6 table

    Impact of magnetic field on the stability of the CMS GE1/1 GEM detector operation

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    The Gas Electron Multiplier (GEM) detectors of the GE1/1 station of the CMS experiment have been operated in the CMS magnetic field for the first time on the 7th^{th} of October 2021. During the magnetic field ramps, several discharge phenomena were observed, leading to instability in the GEM High Voltage (HV) power system. In order to reproduce the behavior, it was decided to conduct a dedicated test at the CERN North Area with the Goliath magnet, using four GE1/1 spare chambers. The test consisted in studying the characteristics of discharge events that occurred in different detector configurations and external conditions. Multiple magnetic field ramps were performed in sequence: patterns in the evolution of the discharge rates were observed with these data. The goal of this test is the understanding of the experimental conditions inducing discharges and short circuits in a GEM foil. The results of this test lead to the development of procedure for the optimal operation and performance of GEM detectors in the CMS experiment during the magnet ramps. Another important result is the estimation of the probability of short circuit generation, at 68 % confidence level, pshort_{short}HV^{HV} OFF^{OFF} = 0.420.35+0.94^{-0.35+0.94}% with detector HV OFF and pshort_{short}HV^{HV} OFF^{OFF} < 0.49% with the HV ON. These numbers are specific for the detectors used during this test, but they provide a first quantitative indication on the phenomenon, and a point of comparison for future studies adopting the same procedure

    CAD-based computer vision: the automatic generation of recognition stragtegies

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    Journal ArticleThree-dimensional model-based computer vision uses geometric models of objects and sensed data to recognize objects in a scene. Likewise, Computer Aided Design (CAD) systems are used to interactively generate three-dimensional models during these fields. Recently, the unification of CAD and vision systems has become the focus of research in the context of manufacturing automation. This paper explores the connection between CAD and computer vision. A method for the automatic generation of recognition strategies based on the geometric properties of shape has been devised and implemented. This uses a novel technique developed for quantifying the following properties of features which compose models used in computer vision: robustness, completeness, consistency, cost, and uniqueness. By utilizing this information, the automatic synthesis of a specialized recognition scheme, called a Strategy Tree, is accomplished. Strategy Trees describe, in a systematic and robust manner. the search process used for recognition and localization of particular objects in the given scene. They consist of selected features which satisfy system constraints and Corroborating Evidence Subtrees which are used in the formation of hypotheses. Verification techniques, used to substantiate or refute these hypotheses, are explored. Experiments utilizing 3-D data are presented
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