299 results on '"Prakash, Arun"'
Search Results
2. Scalar auxiliary variable (SAV) stabilization of implicit-explicit (IMEX) time integration schemes for nonlinear structural dynamics
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Kwon, Sun-Beom and Prakash, Arun
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Mathematics - Numerical Analysis - Abstract
Implicit-explicit (IMEX) time integration schemes are well suited for nonlinear structural dynamics because of their low computational cost and high accuracy. However, stability of IMEX schemes cannot be guaranteed for general nonlinear problems. In this article, we present a scalar auxiliary variable (SAV) stabilization of high-order IMEX time integration schemes that leads to unconditional stability. The proposed IMEX-BDFk-SAV schemes treat linear terms implicitly using kth-order backward difference formulas (BDFk) and nonlinear terms explicitly. This eliminates the need for iterations in nonlinear problems and leads to low computational cost. Truncation error analysis of the proposed IMEX-BDFk-SAV schemes confirms that up to kth-order accuracy can be achieved and this is verified through a series of convergence tests. Unlike existing SAV schemes for first-order ordinary differential equations (ODEs), we introduce a novel SAV for the proposed schemes that allows direct solution of the second-order ODEs without transforming them to a system of first-order ODEs. Finally, we demonstrate the performance of the proposed schemes by solving several nonlinear problems in structural dynamics and show that the proposed schemes can achieve high accuracy at a low computational cost while maintaining unconditional stability., Comment: 48 pages, 17 figures, 3 tables
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- 2024
3. Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19
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Matthay, Zachary A, Fields, Alexander T, Wick, Katherine D, Jones, Chayse, Lane, H Clifford, Herrera, Kimberly, Nuñez-Garcia, Brenda, Gennatas, Efstathios, Hendrickson, Carolyn M, Kornblith, Aaron E, Matthay, Michael A, Kornblith, Lucy Z, Group, the COVID-19 Associated Coagulopathy Inflammation Thrombosis Study, Ambachew, Biniam, Bainton, Roland J, Cary, Sarah, Chalwell, Lauren, Colwell, Christopher, Josephy, Clayton, Kurien, Philip, Lee, Deanna, LeGrand, Matthieu, Montoy, Juan Carlos, Nguyen, Viet, Park, John J, Prakash, Arun, Robinson, Brittany, and India, Shelley
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Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Coronaviruses ,Autoimmune Disease ,Infectious Diseases ,Coronaviruses Disparities and At-Risk Populations ,4.1 Discovery and preclinical testing of markers and technologies ,Infection ,Good Health and Well Being ,Humans ,COVID-19 ,SARS-CoV-2 ,Receptor for Advanced Glycation End Products ,Nucleocapsid ,Antigens ,Biomarkers ,Antigens ,Viral ,biomarkers ,thromboinflammation ,receptor for advanced glycation end products ,triage ,COVID-19 Associated Coagulopathy Inflammation Thrombosis (Co-ACIT) Study Group ,Immunology ,Medical Microbiology ,Biochemistry and cell biology ,Genetics - Abstract
IntroductionThere remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19.MethodsBlood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.ResultsDifferences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p80% on cut-point analysis.DiscussionElevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.
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- 2023
4. Multi-element flow-driven spectral chaos (ME-FSC) method for uncertainty quantification of dynamical systems
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Esquivel, Hugo, Prakash, Arun, and Lin, Guang
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Mathematics - Numerical Analysis - Abstract
The flow-driven spectral chaos (FSC) is a recently developed method for tracking and quantifying uncertainties in the long-time response of stochastic dynamical systems using the spectral approach. The method uses a novel concept called 'enriched stochastic flow maps' as a means to construct an evolving finite-dimensional random function space that is both accurate and computationally efficient in time. In this paper, we present a multi-element version of the FSC method (the ME-FSC method for short) to tackle (mainly) those dynamical systems that are inherently discontinuous over the probability space. In ME-FSC, the random domain is partitioned into several elements, and then the problem is solved separately on each random element using the FSC method. Subsequently, results are aggregated to compute the probability moments of interest using the law of total probability. To demonstrate the effectiveness of the ME-FSC method in dealing with discontinuities and long-time integration of stochastic dynamical systems, four representative numerical examples are presented in this paper, including the Van-der-Pol oscillator problem and the Kraichnan-Orszag three-mode problem. Results show that the ME-FSC method is capable of solving problems that have strong nonlinear dependencies over the probability space, both reliably and at low computational cost., Comment: Preprint submitted to Journal of Computational Physics (Elsevier)
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- 2022
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5. COVID-19–associated Lung Microvascular Endotheliopathy: A “From the Bench” Perspective
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Joffre, Jérémie, Rodriguez, Lauren, Matthay, Zachary A, Lloyd, Elliot, Fields, Alexander T, Bainton, Roland J, Kurien, Philip, Sil, Anita, Calfee, Carolyn S, Woodruff, Prescott G, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Langelier, Charles R, Matthay, Michael A, Kornblith, Lucy Z, Hellman, Judith, Bhide, Sharvari, Carrillo, Sidney A, Chak, Suzanna, Fragiadakis, Gabriela K, Ghale, Rajani, Giberson, Jeremy, Glenn, Pat, Gonzalez, Ana, Jauregui, Alejandra, Jones, Norman, Kangelaris, Kirsten, Ke, Serena, Lea, Tasha, Lee, Deanna, Lelidowicz, Aleskandra, Lota, Raphael, Matthay, Michael, Milush, Jeff, Nguyen, Viet, Rashid, Ahmad Sadeed, Rodriguez, Nicklaus, Sigman, Austin, Tang, Kevin, Altamirano, Luz Torres, Ward, Alyssa, Willmore, Andrew, Wilson, Michael, Ambachew, Biniam, Cary, Sarah, Chalwell, Lauren, Colwell, Christopher, Jones, Chayse, Josephy, Clayton, LeGrand, Matthieu, Montoy, Juan Carlos, Kornblith, Aaron E, Nunez-Garcia, Brenda, Park, John J, Prakash, Arun, Robinson, Brittany, Shelley, India, and Wick, Katherine D
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Medical Microbiology ,Biomedical and Clinical Sciences ,Prevention ,Biodefense ,Pneumonia & Influenza ,Pneumonia ,Acute Respiratory Distress Syndrome ,Vaccine Related ,Infectious Diseases ,Lung ,Rare Diseases ,Clinical Research ,Emerging Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Biomarkers ,COVID-19 ,Endothelial Cells ,Humans ,Inflammation Mediators ,Plasminogen Activator Inhibitor 1 ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Vascular Diseases ,Vascular Endothelial Growth Factor A ,acute respiratory distress syndrome ,endothelial permeability ,lung endothelial injury ,COVID-19 Multi-Phenotyping for Effective Therapies (COMET) Consortium ,COVID-19 Associated Coagulopathy ,Inflammation ,and Thrombosis (Co-ACIT) Study Group ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2; inactivated viral particles; or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.
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- 2022
6. Sintering of Alumina Nanoparticles: Comparison of Interatomic Potentials, Molecular Dynamics Simulations, and Data Analysis
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Roy, Shyamal, Prakash, Arun, and Sandfeld, Stefan
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Condensed Matter - Materials Science - Abstract
Sintering of alumina nanoparticles is of interest both from the view of fundamental research as well as for industrial applications. Atomistic simulations are tailor-made for understanding and predicting the time- and temperature-dependent sintering behaviour. However, the quality and predictability of such analysis is strongly dependent on the performance of the underlying interatomic potentials. In this work, we investigate and benchmark four empirical interatomic potentials and discuss the resulting properties and drawbacks based on experimental and density functional theory data from the literature. The potentials, which have different origins and formulations, are then used in molecular dynamics simulations to perform a systematic study of the sintering process. To analyse the results, we develop a number of tailored data analysis approaches that are able to characterise and quantify the sintering process. Subsequently, the disparities in the sintering behaviour predicted by the potentials are critically discussed. Finally, we conclude by providing explanations for the differences in performance of the potentials, together with recommendations for molecular dynamics sintering simulations of alumina.
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- 2022
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7. Immune regulation of disease tolerance and immune priming in Drosophila
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Prakash, Arun, Vale, Pedro, Wilson, Amy B. Pedersen, and Regan, Jenny
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Disease tolerance ,negative immune regulation ,immune priming ,tissue damage repair ,pathogen transmission - Abstract
To regain health following infection, hosts must not only identify and eliminate the source of infection, but also be able to reduce the resulting tissue damage in order to tolerate immunopathology. Compared to the mechanisms of pathogen clearance, we currently know less about how the mechanisms of damage prevention and repair contribute to disease tolerance phenotype. The aim of this thesis is to improve our understanding of mechanisms that enhance disease tolerance during bacterial infections. Here, I employed genetically manipulated fruit flies (Drosophila melanogaster) with disrupted mechanisms of immune regulation, damage prevention and repair to test how these mechanisms contribute to disease tolerance. We find that reduced expression of the negative regulators of IMD (immune deficiency pathway) or absence of regulation of Jak/Stat (Janus kinase/signal transducer and activator of transcription pathway), severely reduced the ability of flies to tolerate systemic infection with Pseudomonas entomophila. Therefore, in addition to regulating an efficient pathogen clearance response, negative immune regulators also contribute to disease tolerance. We also found that loss-of-function mutants lacking damage preventing dcy (drosocrystallin - a major component of the peritrophic matrix), damage signalling upd3 (unpaired protein, a cytokine-like molecule), damage repairing egfr1 (epidermal growth factor receptor) and damage controlling irc (immune-regulated catalase, a negative regulator of reactive oxygen species), affect the ability of flies to tolerate enteric infection, and that these effects are sexually dimorphic. Finally, we also investigated an additional defence mechanism of immune priming in Drosophila. Using UAS-RNAi knockdown, loss-of-function or immune deletion mutants and CRISPR knockout transgenic flies we found that immune priming is a long-lasting response, occurring in several backgrounds and is particularly stronger in male flies. Priming requires the regulation of the IMD-responsive antimicrobial peptide Diptercin in the fat body against the gram-negative bacteria Providencia rettgeri. We further found that priming has the potential to reduce disease spread and transmission by affecting pathogen shedding. The thesis concludes with an outlook on future research in the field of disease tolerance and damage limitation mechanisms to bacterial infections in Drosophila.
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- 2022
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8. Teaching computing for complex problems in civil engineering and geosciences using big data and machine learning: synergizing four different computing paradigms and four different management domains
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Babović, Zoran, Bajat, Branislav, Barac, Dusan, Bengin, Vesna, Đokić, Vladan, Đorđević, Filip, Drašković, Dražen, Filipović, Nenad, French, Stephan, Furht, Borko, Ilić, Marija, Irfanoglu, Ayhan, Kartelj, Aleksandar, Kilibarda, Milan, Klimeck, Gerhard, Korolija, Nenad, Kotlar, Miloš, Kovačević, Miloš, Kuzmanović, Vladan, Lehn, Jean-Marie, Madić, Dejan, Marinković, Marko, Mateljević, Miodrag, Mendelson, Avi, Mesinger, Fedor, Milovanović, Gradimir, Milutinović, Veljko, Mitić, Nenad, Nešković, Aleksandar, Nešković, Nataša, Nikolić, Boško, Novoselov, Konstantin, Prakash, Arun, Protić, Jelica, Ratković, Ivan, Rios, Diego, Shechtman, Dan, Stojadinović, Zoran, Ustyuzhanin, Andrey, and Zak, Stan
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- 2023
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9. Research in computing-intensive simulations for nature-oriented civil-engineering and related scientific fields, using machine learning and big data: an overview of open problems
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Babović, Zoran, Bajat, Branislav, Đokić, Vladan, Đorđević, Filip, Drašković, Dražen, Filipović, Nenad, Furht, Borko, Gačić, Nikola, Ikodinović, Igor, Ilić, Marija, Irfanoglu, Ayhan, Jelenković, Branislav, Kartelj, Aleksandar, Klimeck, Gerhard, Korolija, Nenad, Kotlar, Miloš, Kovačević, Miloš, Kuzmanović, Vladan, Marinković, Marko, Marković, Slobodan, Mendelson, Avi, Milutinović, Veljko, Nešković, Aleksandar, Nešković, Nataša, Mitić, Nenad, Nikolić, Boško, Novoselov, Konstantin, Prakash, Arun, Ratković, Ivan, Stojadinović, Zoran, Ustyuzhanin, Andrey, and Zak, Stan
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- 2023
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10. Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance in Early Human Sepsis
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Leligdowicz, Aleksandra, Kamm, Jack, Kalantar, Katrina, Jauregui, Alejandra, Vessel, Kathryn, Caldera, Saharai, Serpa, Paula Hayakawa, Abbott, Jason, Fang, Xiaohui, Tian, Xiaoli, Prakash, Arun, Kangelaris, Kirsten Neudoerffer, Liu, Kathleen D, Calfee, Carolyn S, Langelier, Charles, and Matthay, Michael A
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Biomedical and Clinical Sciences ,Immunology ,Genetics ,Clinical Research ,Sepsis ,Infectious Diseases ,Hematology ,Aetiology ,4.1 Discovery and preclinical testing of markers and technologies ,2.1 Biological and endogenous factors ,Detection ,screening and diagnosis ,Inflammatory and immune system ,Endotoxin Tolerance ,Endotoxins ,Humans ,Immune Tolerance ,Immunity ,Inflammation ,Lipopolysaccharides ,Transcriptome ,Endotoxin tolerance ,immune system ,RNA expression ,sepsis ,Clinical Sciences ,Emergency & Critical Care Medicine ,Clinical sciences - Abstract
BackgroundLimited studies have functionally evaluated the heterogeneity in early ex vivo immune responses during sepsis. Our aim was to characterize early sepsis ex vivo functional immune response heterogeneity by studying whole blood endotoxin responses and derive a transcriptional metric of ex vivo endotoxin response.MethodsBlood collected within 24 h of hospital presentation from 40 septic patients was divided into two fractions and incubated with media (unstimulated) or endotoxin. Supernatants and cells were isolated, and responses measured using: supernatant cytokines, lung endothelial permeability after supernatant exposure, and RNA expression. A transcriptomic signature was derived in unstimulated cells to predict the ex vivo endotoxin response. The signature was tested in a separate cohort of 191 septic patients to evaluate for association with clinical outcome. Plasma biomarkers were quantified to measure in vivo host inflammation.ResultsEx vivo response to endotoxin varied and was unrelated to immunosuppression, white blood cell count, or the causative pathogen. Thirty-five percent of patients demonstrated a minimal response to endotoxin, suggesting early immunosuppression. High ex vivo cytokine production by stimulated blood cells correlated with increased in vitro pulmonary endothelial cell permeability and was associated with attenuated in vivo host inflammation. A four-gene signature of endotoxin response detectable without the need for a functional assay was identified. When tested in a separate cohort of septic patients, its expression was inversely associated with hospital mortality.ConclusionsAn attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome.
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- 2022
11. A Mouse Model of Orotracheal Intubation and Ventilated Lung Ischemia Reperfusion Surgery.
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Liao, Wen-I, Maruyama, Daisuke, Kianian, Farzaneh, Tat, Christine, Tian, Xiaoli, Hellman, Judith, Dodd-O, Jeffrey M, and Prakash, Arun
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Biochemistry and Cell Biology ,Biological Sciences ,Lung ,Respiratory ,Animals ,Disease Models ,Animal ,Intubation ,Intratracheal ,Ischemia ,Lung Diseases ,Mice ,Reperfusion ,Reperfusion Injury ,Psychology ,Cognitive Sciences ,Biochemistry and cell biology - Abstract
Ischemia reperfusion (IR) injury frequently results from processes that involve a transient period of interrupted blood flow. In the lung, isolated IR permits the experimental study of this specific process with continued alveolar ventilation, thereby avoiding the compounding injurious processes of hypoxia and atelectasis. In the clinical context, lung ischemia reperfusion injury (also known as lung IRI or LIRI) is caused by numerous processes, including but not limited to pulmonary embolism, resuscitated hemorrhagic trauma, and lung transplantation. There are currently limited effective treatment options for LIRI. Here, we present a reversible surgical model of lung IR involving first orotracheal intubation followed by unilateral left lung ischemia and reperfusion with preserved alveolar ventilation or gas exchange. Mice undergo a left thoracotomy, through which the left pulmonary artery is exposed, visualized, isolated, and compressed using a reversible slipknot. The surgical incision is then closed during the ischemic period, and the animal is awakened and extubated. With the mouse spontaneously breathing, reperfusion is established by releasing the slipknot around the pulmonary artery. This clinically relevant survival model permits the evaluation of lung IR injury, the resolution phase, downstream effects on lung function, as well as two-hit models involving experimental pneumonia. While technically challenging, this model can be mastered over the course of a few weeks to months with an eventual survival or success rate of 80%-90%.
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- 2022
12. Flow-driven spectral chaos (FSC) method for long-time integration of second-order stochastic dynamical systems
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Esquivel, Hugo, Prakash, Arun, and Lin, Guang
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Mathematics - Numerical Analysis - Abstract
For decades, uncertainty quantification techniques based on the spectral approach have been demonstrated to be computationally more efficient than the Monte Carlo method for a wide variety of problems, particularly when the dimensionality of the probability space is relatively low. The time-dependent generalized polynomial chaos (TD-gPC) is one such technique that uses an evolving orthogonal basis to better represent the stochastic part of the solution space in time. In this paper, we present a new numerical method that uses the concept of 'enriched stochastic flow maps' to track the evolution of the stochastic part of the solution space in time. The computational cost of this proposed flow-driven stochastic chaos (FSC) method is an order of magnitude lower than TD-gPC for comparable solution accuracy. This gain in computational cost is realized because, unlike most existing methods, the number of basis vectors required to track the stochastic part of the solution space, and consequently the computational cost associated with the solution of the resulting system of equations, does not depend upon the dimensionality of the probability space. Four representative numerical examples are presented to demonstrate the performance of the FSC method for long-time integration of second-order stochastic dynamical systems in the context of stochastic dynamics of structures., Comment: Preprint submitted to Journal of Computational and Applied Mathematics (Elsevier). arXiv admin note: text overlap with arXiv:2012.01496
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- 2021
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13. Flow-driven spectral chaos (FSC) method for simulating long-time dynamics of arbitrary-order non-linear stochastic dynamical systems
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Esquivel, Hugo, Prakash, Arun, and Lin, Guang
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Mathematics - Numerical Analysis ,Physics - Computational Physics - Abstract
Uncertainty quantification techniques such as the time-dependent generalized polynomial chaos (TD-gPC) use an adaptive orthogonal basis to better represent the stochastic part of the solution space (aka random function space) in time. However, because the random function space is constructed using tensor products, TD-gPC-based methods are known to suffer from the curse of dimensionality. In this paper, we introduce a new numerical method called the 'flow-driven spectral chaos' (FSC) which overcomes this curse of dimensionality at the random-function-space level. The proposed method is not only computationally more efficient than existing TD-gPC-based methods but is also far more accurate. The FSC method uses the concept of 'enriched stochastic flow maps' to track the evolution of a finite-dimensional random function space efficiently in time. To transfer the probability information from one random function space to another, two approaches are developed and studied herein. In the first approach, the probability information is transferred in the mean-square sense, whereas in the second approach the transfer is done exactly using a new theorem that was developed for this purpose. The FSC method can quantify uncertainties with high fidelity, especially for the long-time response of stochastic dynamical systems governed by ODEs of arbitrary order. Six representative numerical examples, including a nonlinear problem (the Van-der-Pol oscillator), are presented to demonstrate the performance of the FSC method and corroborate the claims of its superior numerical properties. Finally, a parametric, high-dimensional stochastic problem is used to demonstrate that when the FSC method is used in conjunction with Monte Carlo integration, the curse of dimensionality can be overcome altogether., Comment: Preprint submitted to Journal of Computational Physics (Elsevier). This is an updated version of the journal article (for more information, see the Errata sheet included at the end of the document)
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- 2020
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14. Duox and Jak/Stat signalling influence disease tolerance in Drosophila during Pseudomonas entomophila infection
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Prakash, Arun, Monteith, Katy M., Bonnet, Mickael, and Vale, Pedro F.
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- 2023
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15. A journey upstream: Fluctuating platelet-specific genes in cell-free plasma as proof-of-concept for using ribonucleic acid sequencing to improve understanding of postinjury platelet biology.
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Kornblith, Lucy Zumwinkle, Bainton, Cedric MV, Fields, Alexander T, Matthay, Zachary A, Magid, Nina T, Nunez-Garcia, Brenda, Prakash, Arun, Kurien, Philip A, Callcut, Rachael A, Cohen, Mitchell J, and Bainton, Roland J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Traumatic Brain Injury (TBI) ,Genetics ,Physical Injury - Accidents and Adverse Effects ,Brain Disorders ,Traumatic Head and Spine Injury ,Adult ,Blood Coagulation Disorders ,Blood Platelets ,Brain Injuries ,Traumatic ,Case-Control Studies ,Cell-Free Nucleic Acids ,Female ,Humans ,Injury Severity Score ,Liquid Biopsy ,Longitudinal Studies ,Male ,Platelet Activation ,Platelet Aggregation ,Proof of Concept Study ,Prospective Studies ,RNA Splicing ,RNA-Seq ,Young Adult ,Platelet activation ,next generation sequencing ,ribonucleic acid sequencing ,cell-free plasma ,prespliced RNA complexes ,dynamically regulated RNA splicing ,Clinical sciences ,Nursing - Abstract
BackgroundThe mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell-free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of postinjury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared with minimally injured trauma controls (t-controls), filtered by healthy control (h-control) data sets.MethodsHigh-read depth RNA sequencing was applied to CFP from 10 patients with fTBI (Abbreviated Injury Scale [AIS] for head ≥3, AIS for all other categories
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- 2020
16. Litsea salicifolia Roxb. bark ethanolic extract attenuates rheumatoid arthritis by inhibiting TLR4/NF-κB and activating SIRT1-Nrf2/HO-1 signaling axis: In-vitro and in-vivo evaluations
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Puppala, Eswara Rao, Abubakar, Md., Swamy, Veerabhadra, Yalamarthi, Sai Sudha, NP, Syamprasad, Prakash, Arun N., Gangasani, Jagadeesh Kumar, Chamundeswari, D., and Naidu, V.G.M.
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- 2023
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17. An adaptive and cooperative MAC protocol for safety applications in cognitive radio enabled vehicular Ad-hoc networks
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Tiwari, Jahnvi, Prakash, Arun, and Tripathi, Rajeev
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- 2023
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18. IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission
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Prakash, Arun, primary, Fenner, Florence, additional, Shit, Biswajit, additional, Salminen, Tiina S., additional, Monteith, Katy M., additional, Khan, Imroze, additional, and Vale, Pedro F., additional
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- 2024
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19. Corrigendum: Elevated Gut Microbiome-Derived Propionate Levels Are Associated With Reduced Sterile Lung Inflammation and Bacterial Immunity in Mice
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Tian, Xiaoli, Hellman, Judith, Horswill, Alexander R, Crosby, Heidi A, Francis, Kevin P, and Prakash, Arun
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Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,lung injury ,short-chain fatty acids ,SCFA ,acetate ,propionate ,IR ,inflammation ,Environmental Science and Management ,Soil Sciences ,Medical microbiology - Abstract
[This corrects the article DOI: 10.3389/fmicb.2019.00159.].
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- 2019
20. Elevated Gut Microbiome-Derived Propionate Levels Are Associated With Reduced Sterile Lung Inflammation and Bacterial Immunity in Mice.
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Tian, Xiaoli, Hellman, Judith, Horswill, Alexander R, Crosby, Heidi A, Francis, Kevin P, and Prakash, Arun
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IR ,SCFA ,acetate ,inflammation ,lung injury ,propionate ,short-chain fatty acids ,Emerging Infectious Diseases ,Biodefense ,Infectious Diseases ,Nutrition ,Prevention ,Vaccine Related ,Lung ,Development of treatments and therapeutic interventions ,1.1 Normal biological development and functioning ,Aetiology ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Underpinning research ,Respiratory ,Infection ,Inflammatory and immune system ,Environmental Science and Management ,Soil Sciences ,Microbiology - Abstract
Short-chain fatty acids (SCFA) are important dietary and microbiome metabolites that can have roles in gut immunity as well as further afield. We previously observed that gut microbiome alteration via antibiotics led to attenuated lung inflammatory responses. The rationale for this study was to identify gut microbiome factors that regulate lung immune homeostasis. We first investigated key factors within mouse colonic lumen filtrates (CLF) which could elicit direct inflammatory effects in vitro. We identified lipopolysaccharide (LPS) and SCFAs as key CLF ingredients whose levels and inflammatory capacity changed after antibiotic exposure in mice. Specifically, the SCFA propionate appeared to be a key regulator of LPS responses in vitro. Elevated propionate: acetate ratios, as seen in CLF after antibiotic exposure, strongly blunted inflammatory responses in vitro. In vivo, exposure of lungs to high dose propionate, to mimic how prior antibiotic exposure changed SCFA levels, resulted in diminished immune containment of Staphylococcus aureus pneumonia. Finally, we discovered an enrichment of propionate-producing gut bacteria in mice with reduced lung inflammation following lung ischemia reperfusion injury in vivo. Overall, our data show that propionate levels can distinctly modulate lung immune responses in vitro and in vivo and that gut microbiome increased production of propionate is associated with reduced lung inflammation.
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- 2019
21. On component isolation of conceptual advanced reactors
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Shrestha, Samyog, Kurt, Efe G., Prakash, Arun, and Irfanoglu, Ayhan
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- 2022
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22. A novel slot scheduling technique for duty-cycle based data transmission for wireless sensor network
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Tripathi, Yogesh, Prakash, Arun, and Tripathi, Rajeev
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- 2022
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23. A cross layer based cooperative broadcast protocol for multichannel VANET
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Srivastava, Ankita, Prakash, Arun, and Tripathi, Rajeev
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- 2022
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24. The costs and benefits of basal infection resistance vs immune priming responses in an insect
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Prakash, Arun, Agashe, Deepa, and Khan, Imroze
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- 2022
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25. Why do insects evolve immune priming? A search for crossroads
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Prakash, Arun and Khan, Imroze
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- 2022
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26. An observational study assessing distribution of mosquito bites on humans to inform personal protection measures against malaria and dengue vectors
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Sadik, Mydeen, primary, Raj, Antony Stephen, additional, Sahani, Govardhan, additional, Prakash, Arun, additional, Mohammed, Fiaz, additional, and Allam, Ramakrishna, additional
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- 2024
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27. N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1.
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Lawton, Samira, Xu, Fengyun, Tran, Alphonso, Wong, Erika, Prakash, Arun, Schumacher, Mark, Wilhelmsen, Kevin, and Hellman, Judith
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Acute Disease ,Animals ,Arachidonic Acids ,Calcitonin Gene-Related Peptide ,Disease Models ,Animal ,Dopamine ,Inflammation ,Lipopeptides ,Lipopolysaccharides ,Mice ,Plasminogen Activator Inhibitor 1 ,Sepsis ,Substance P ,TRPV Cation Channels - Abstract
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADAs anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation.
- Published
- 2017
28. NLRP3 Inflammasome Mediates Dormant Neutrophil Recruitment following Sterile Lung Injury and Protects against Subsequent Bacterial Pneumonia in Mice.
- Author
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Tian, Xiaoli, Sun, He, Casbon, Amy-Jo, Lim, Edward, Francis, Kevin P, Hellman, Judith, and Prakash, Arun
- Subjects
LRR- ,NOD- ,and pyrin domain-containing 3 ,inflammasome ,inflammation ,interleukin-1β ,ischemia–reperfusion ,lung injury ,neutrophil activation ,Lung ,Pneumonia ,Infectious Diseases ,Pneumonia & Influenza ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Inflammatory and immune system ,Respiratory ,interleukin-1 beta ,ischemia-reperfusion ,Immunology ,Medical Microbiology - Abstract
Sterile lung injury is an important clinical problem that complicates the course of severely ill patients. Interruption of blood flow, namely ischemia-reperfusion (IR), initiates a sterile inflammatory response in the lung that is believed to be maladaptive. The rationale for this study was to elucidate the molecular basis for lung IR inflammation and whether it is maladaptive or beneficial. Using a mouse model of lung IR, we demonstrate that sequential blocking of inflammasomes [specifically, NOD-, LRR-, and pyrin domain-containing 3 (NLRP3)], inflammatory caspases, and interleukin (IL)-1β, all resulted in an attenuated inflammatory response. IL-1β production appeared to predominantly originate in conjunction with alveolar type 2 epithelial cells. Lung IR injury recruited unactivated or dormant neutrophils producing less reactive oxygen species thereby challenging the notion that recruited neutrophils are terminally activated. However, lung IR inflammation was able to limit or reduce the bacterial burden from subsequent experimentally induced pneumonia. Notably, inflammasome-deficient mice were unable to alter this bacterial burden following IR. Thus, we conclude that the NLRP3 inflammasome, through IL-1β production, regulates lung IR inflammation, which includes recruitment of dormant neutrophils. The sterile IR inflammatory response appears to serve an important function in inducing resistance to subsequent bacterial pneumonia and may constitute a critical part of early host responses to infection in trauma.
- Published
- 2017
29. Fuzzy-based beaconless probabilistic broadcasting for information dissemination in urban VANET
- Author
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Srivastava, Ankita, Prakash, Arun, and Tripathi, Rajeev
- Published
- 2020
- Full Text
- View/download PDF
30. Application of Plant-Based Hydrocolloids on the Textural Profile of Vegan Gummies Supplemented with Turmeric and Black Pepper.
- Author
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Rawat, Santoshi, Rai, Sweta, Sangeeta, Sabbu, Kumar, Anil, Ramachandran, Preethi, Sharma, Satish Kumar, Dubey, Shiv Kumar, Prakash, Arun, and Joshi, Riya
- Subjects
HYDROCOLLOIDS ,GUAR gum ,TURMERIC ,AGAR ,FUNCTIONAL foods ,OXIDANT status - Abstract
Gummies belong to a confectionery category characterized by a hydrocolloid, acting as a stabilizer, forming a network to retain a high-moisture sugar syrup, and hydrocolloids play a key role in shaping the visual appeal, flavour release, and texture of the gel network. This study investigates the potential substitution of gelatin in gummies with plant-based hydrocolloids like agar-agar and guar gum. It is also aimed at optimizing the level of functional ingredients like curcumin and piperine in standardized gummies through incorporation of turmeric and black pepper, respectively. These plant-based gelling agents mimic gelatin's chewable, firm, and elastic texture, catering to broader consumption and suitability for versatile use. Consumer interest in healthier diets has spurred the transition towards plant-based functional foods, leading to the replacement of gelatin gummies with plant-based alternatives. Agar-agar significantly influences gummy texture by contributing to firmness, elasticity, and stable gel formation, imparting essential strength and consistency. Guar gum, recognized as a plant-based hydrocolloid, enhances gummy texture, consistency, and moisture retention through thickening and stabilization. While agar-agar and guar gum individually fell short in achieving the desired textural attributes in the gummies, their combined use (1% agar-agar and 5.5% guar gum) yielded optimal chewiness (1,455.12 ± 1.75 N), gumminess (2251.11 ± 2.14 N), and high overall acceptability (8.96), resembling gelatin-based gummies. The optimized formulation included 40% sugar, 2% citric acid, 2% turmeric, and 0.6% black pepper. The developed vegan gummies contained 56.9 ± 0.09 mg/100 g total phenols, 37.27 ± 1.4 % antioxidant capacity, 0.054 ± 0.0012 % curcumin, and 0.02 ± 0.008 % piperine. Consequently, the combined use of agar-agar and guar gum emerged as stable and effective gelling agents, offering an alternative to gelatin for creating turmeric and black pepper-infused gummies with desirable texture and functional attributes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Role of IL-1β and the gut-lung axis in sterile inflammation following lung ischemia reperfusion injury
- Author
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Prakash, Arun, Tian, Xiaoli, and Hellman, Judith
- Subjects
Digestive Diseases ,Lung ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Good Health and Well Being ,Immunology - Abstract
Abstract: Background: Ischemia reperfusion (IR) injury is a source of sterile inflammation that can complicate the clinical course of severely injured trauma patients in shock, organ transplantation, and thrombotic/embolic events. The lungs are a portal to the external environment and a barrier organ. As such, they are vulnerable to infectious and sterile insults that can be life threatening if their ability to deliver oxygen and eliminate CO2 are compromised. We previously demonstrated a role for the gut microbiome in modulating this inflammatory process in vivo and in priming alveolar macrophages. Methods: We used an in vivo model of left pulmonary artery occlusion to examine the inflammation generated in mice either genetically deficient or pharmacologically inhibited in IL-1β release or signaling pathways. We also challenged alveolar macrophages and endothelial cells in vitro with colonic lumen filtrates from antibiotic treated and control mice to determine whether shed LPS and metabolites are among the priming factor(s) for alveolar macrophages. Results/Conclusions: Using knockout mice and inhibitor studies, we have determined that the inflammasome regulates lung IR-induced sterile inflammation. Specifically, the NLRP3 inflammasome, IL-1β release, and downstream IL-1β signaling are important factors in the generation of lung IR inflammation. Finally, we believe that the exponentially higher level of shed LPS in mice with a full complement of gut microbiota, as well as levels of short chain fatty acids, such as butyrate, may intriguingly explain the priming of alveolar macrophages that results in IL-1β production. Together this may constitute a gut-lung axis of communication that modulates the lung IR sterile inflammatory process.
- Published
- 2016
32. Role of IL-1 beta and the gut-lung axis in sterile inflammation following lung ischemia reperfusion injury
- Author
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Prakash, Arun, Tian, Xiaoli, and Hellman, Judith
- Subjects
Immunology - Published
- 2016
33. Lung Ischemia-Reperfusion is a Sterile Inflammatory Process Influenced by Commensal Microbiota in Mice.
- Author
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Prakash, Arun, Sundar, Shirin V, Zhu, Ying-Gang, Tran, Alphonso, Lee, Jae-Woo, Lowell, Clifford, and Hellman, Judith
- Subjects
Intestines ,Lung ,Cells ,Cultured ,Macrophages ,Alveolar ,Animals ,Mice ,Inbred Strains ,Pneumonia ,Reperfusion Injury ,Inflammation Mediators ,Chemokines ,Cytokines ,Anti-Bacterial Agents ,Symbiosis ,Macrophage Activation ,Neutrophil Infiltration ,Male ,Toll-Like Receptor 2 ,Toll-Like Receptor 4 ,Inflammasomes ,Microbiota ,Infectious Diseases ,Cardiovascular ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Clinical Sciences ,Emergency & Critical Care Medicine - Abstract
Lung ischemia-reperfusion (IR) complicates numerous clinical processes, such as cardiac arrest, transplantation, and major trauma. These conditions generate sterile inflammation, which can cause or worsen acute lung injury. We previously reported that lung and systemic inflammation in a mouse model of ventilated lung IR depends on Toll-like receptor 4 (TLR-4) signaling and the presence of alveolar macrophages. Here, we tested the hypothesis that the intestinal microbiome has a role in influencing the inflammatory response to lung IR. Lung IR was created in intubated mechanically ventilated mice via reversible left pulmonary artery occlusion followed by reperfusion. Inflammatory markers and histology were tracked during varying periods of reperfusion (from 1 to 24 h). Separate groups of mice were given intestinally localized antibiotics for 8 to 10 weeks and then were subjected to left lung IR and analysis of lungs and plasma for markers of inflammation. Alveolar macrophages from antibiotic-treated or control mice were tested ex vivo for inflammatory responses to bacterial TLR agonists, namely, lipopolysaccharide and Pam3Cys. We found that inflammation generated by left lung IR was rapid in onset and dissipated within 12 to 24 h. Treatment of mice with intestinally localized antibiotics was associated with a marked attenuation of circulating and lung inflammatory markers as well as reduced histologic evidence of infiltrating cells and edema in the lung after IR. Alveolar macrophages from antibiotic-treated mice produced less cytokines ex vivo when stimulated with TLR agonists as compared with those from control mice. Our data indicate that the inflammatory response induced by nonhypoxic lung IR is transient and is strongly influenced by intestinal microbiota. Furthermore, these data suggest that the intestinal microbiome could potentially be manipulated to attenuate the post-IR pulmonary inflammatory response.
- Published
- 2015
34. Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation.
- Author
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Wilhelmsen, Kevin, Xu, Fengyun, Farrar, Katherine, Tran, Alphonso, Khakpour, Samira, Sundar, Shirin, Prakash, Arun, Wang, Jinhua, Gray, Nathanael, and Hellman, Judith
- Subjects
Animals ,Human Umbilical Vein Endothelial Cells ,Humans ,Interleukin-1beta ,Male ,Mice ,Mitogen-Activated Protein Kinase 7 ,Monocytes ,Systemic Inflammatory Response Syndrome ,Toll-Like Receptor 2 ,Tumor Necrosis Factor-alpha - Abstract
Inflammatory critical illness is a syndrome that is characterized by acute inflammation and organ injury, and it is triggered by infections and noninfectious tissue injury, both of which activate innate immune receptors and pathways. Although reports suggest an anti-inflammatory role for the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5), we previously found that ERK5 mediates proinflammatory responses in primary human cells in response to stimulation of Toll-like receptor 2 (TLR2). We inhibited the kinase activities and reduced the abundances of ERK5 and MEK5, a MAPK kinase directly upstream of ERK5, in primary human vascular endothelial cells and monocytes, and found that ERK5 promoted inflammation induced by a broad range of microbial TLR agonists and by the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Furthermore, we found that inhibitors of MEK5 or ERK5 reduced the plasma concentrations of proinflammatory cytokines in mice challenged with TLR ligands or heat-killed Staphylococcus aureus, as well as in mice that underwent sterile lung ischemia-reperfusion injury. Finally, we found that inhibition of ERK5 protected endotoxemic mice from death. Together, our studies support a proinflammatory role for ERK5 in primary human endothelial cells and monocytes, and suggest that ERK5 is a potential therapeutic target in diverse disorders that cause inflammatory critical illness.
- Published
- 2015
35. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.
- Author
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Kangelaris, Kirsten Neudoerffer, Prakash, Arun, Liu, Kathleen D, Aouizerat, Bradley, Woodruff, Prescott G, Erle, David J, Rogers, Angela, Seeley, Eric J, Chu, Jeffrey, Liu, Tom, Osterberg-Deiss, Thomas, Zhuo, Hanjing, Matthay, Michael A, and Calfee, Carolyn S
- Subjects
Neutrophils ,Humans ,Sepsis ,Acute-Phase Proteins ,Proto-Oncogene Proteins ,RNA ,Messenger ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Lipocalins ,Molecular Sequence Annotation ,Transcriptome ,Biomarkers ,Lipocalin-2 ,Respiratory Distress Syndrome ,ARDS ,gene expression ,neutrophils ,sepsis ,Clinical Research ,Infectious Diseases ,Rare Diseases ,Acute Respiratory Distress Syndrome ,Genetics ,Hematology ,Lung ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Respiratory System ,Physiology ,Medical Physiology - Abstract
The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate
- Published
- 2015
36. Mapping the functional form of the trade-off between infection resistance and reproductive fitness under dysregulated immune signaling.
- Author
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Critchlow, Justin T., Prakash, Arun, Zhong, Katherine Y., and Tate, Ann T.
- Subjects
- *
RED flour beetle , *REPRODUCTION , *IMMUNOREGULATION , *TRIBOLIUM , *IMMUNE response , *DRUG resistance in bacteria - Abstract
Immune responses benefit organismal fitness by clearing parasites but also exact costs associated with immunopathology and energetic investment. Hosts manage these costs by tightly regulating the induction of immune signaling to curtail excessive responses and restore homeostasis. Despite the theoretical importance of turning off the immune response to mitigate these costs, experimentally connecting variation in the negative regulation of immune responses to organismal fitness remains a frontier in evolutionary immunology. In this study, we used a dose-response approach to manipulate the RNAi-mediated knockdown efficiency of cactus (IκBα), a central regulator of Toll pathway signal transduction in flour beetles (Tribolium castaneum). By titrating cactus activity across four distinct levels, we derived the shape of the relationship between immune response investment and traits associated with host fitness, including infection susceptibility, lifespan, fecundity, body mass, and gut homeostasis. Cactus knock-down increased the overall magnitude of inducible immune responses and delayed their resolution in a dsRNA dose-dependent manner, promoting survival and resistance following bacterial infection. However, these benefits were counterbalanced by dsRNA dose-dependent costs to lifespan, fecundity, body mass, and gut integrity. Our results allowed us to move beyond the qualitative identification of a trade-off between immune investment and fitness to actually derive its functional form. This approach paves the way to quantitatively compare the evolution and impact of distinct regulatory elements on life-history trade-offs and fitness, filling a crucial gap in our conceptual and theoretical models of immune signaling network evolution and the maintenance of natural variation in immune systems. Author summary: The immune system provides defense against infection but demands substantial energy and can inadvertently harm the host. To limit these costly side effects, hosts use regulatory proteins that dampen immune responses after they respond to infection. Despite the importance of these regulating proteins, we do not understand how their variation influences infection defense and the broader effects on an organism's health, reproduction, and fitness. We used a novel approach to vary the expression of the regulatory protein cactus, thereby adjusting the magnitude of Toll pathway activation in the red flour beetle. We found that while increasing the intensity of immune pathway activation enhances immune output and survival to bacterial infection, it comes at a disproportionally severe cost to female egg production, gut health, body mass, and lifespan. This reveals that even small variations in negative regulation and immune pathway activation can have disproportionate health and reproductive consequences, helping us better understand how immune systems evolved and the diversity of rules governing their regulation in nature. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Experimental evolution of insect immune memory versus pathogen resistance
- Author
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Khan, Imroze, Prakash, Arun, and Agashe, Deepa
- Published
- 2017
38. Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of near-infrared nanoparticles
- Author
-
Zhang, Ning, Francis, Kevin P, Prakash, Arun, and Ansaldi, Daniel
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Nanotechnology ,Bioengineering ,Animals ,Female ,Luminescent Measurements ,Luminol ,Mice ,Mice ,Inbred BALB C ,Mice ,Inbred C57BL ,Mice ,Knockout ,Mice ,Nude ,Nanoparticles ,Neoplasm Metastasis ,Neoplasms ,Experimental ,Peroxidase ,Pneumonia ,Spectroscopy ,Near-Infrared ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
A previous study reported the use of luminol for the detection of myeloperoxidase (MPO) activity using optical imaging in infiltrating neutrophils under inflammatory disease conditions. The detection is based on a photon-emitting reaction between luminol and an MPO metabolite. Because of tissue absorption and scattering, however, luminol-emitted blue light can be efficiently detected from superficial inflammatory foci only. In this study we report a chemiluminescence resonance energy transfer (CRET) methodology in which luminol-generated blue light excites nanoparticles to emit light in the near-infrared spectral range, resulting in remarkable improvement of MPO detectability in vivo. CRET caused a 37-fold increase in luminescence emission over luminol alone in detecting MPO activity in lung tissues after lipopolysaccharide challenge. We demonstrated a dependence of the chemiluminescent signal on MPO activity using MPO-deficient mice. In addition, co-administration of 4-aminobenzoic acid hydrazide (4-ABAH), an irreversible inhibitor of MPO, significantly attenuated luminescent emission from inflamed lungs. Inhibition of nitric oxide synthase with a nonspecific inhibitor, L-NAME, had no effect on luminol-mediated chemiluminescence production. Pretreatment of mice with MLN120B, a selective inhibitor of IKK-2, resulted in suppression of neutrophil infiltration to the lung tissues and reduction of MPO activity. We also demonstrated that CRET can effectively detect MPO activity at deep tissue tumor foci due to tumor development-associated neutrophil infiltration. We developed a sensitive MPO detection methodology that provides a means for visualizing and quantifying oxidative stress in deep tissue. This method is amenable to rapid evaluation of anti-inflammatory agents in animal models.
- Published
- 2013
39. Alveolar Macrophages and Toll-like Receptor 4 Mediate Ventilated Lung Ischemia Reperfusion Injury in Mice
- Author
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Prakash, Arun, Mesa, Kailin R, Wilhelmsen, Kevin, Xu, Fengyun, Dodd-o, Jeffrey M, and Hellman, Judith
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Physical Injury - Accidents and Adverse Effects ,Rare Diseases ,Acute Respiratory Distress Syndrome ,Lung ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Respiratory ,Acute Lung Injury ,Analgesics ,Non-Narcotic ,Animals ,CD11 Antigens ,Cell Line ,Clodronic Acid ,Cytokines ,Enzyme-Linked Immunosorbent Assay ,Flow Cytometry ,Humans ,Liposomes ,Macrophages ,Alveolar ,Mice ,Mice ,Knockout ,Neutrophil Infiltration ,Nutritional Status ,Pulmonary Atelectasis ,Pulmonary Circulation ,Real-Time Polymerase Chain Reaction ,Reperfusion Injury ,Respiration ,Artificial ,Toll-Like Receptor 2 ,Toll-Like Receptor 4 ,Anesthesiology ,Clinical sciences - Abstract
BackgroundIschemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens.MethodsThe authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients.ResultsCompared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury.ConclusionsThe data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury.
- Published
- 2012
40. Prolonged Profound Hypoxia and Cardiac Failure in a Young Woman Presenting to the Emergency Department
- Author
-
Breyer, Kristine EW, Ou, Joel, Durack, Jeremy C, and Prakash, Arun
- Subjects
Emergency Care ,Lung ,Cardiovascular ,Clinical Research - Abstract
Pulmonary emboli are rare occurrences in young patients, especially those who present precipitously to the emergency department. In a young unresponsive patient, recognition of thromboembolic etiology may be delayed due to atypical presenting physiology or competing diagnoses. In this report, the authors describe an initially confounding case of catastrophic bilateral pulmonary emboli in a young woman who presented to the emergency department having been found unconscious on the street. Despite severe and prolonged hypoxia as well as multi-organ failure, the patient achieved a near complete recovery. © 2012 The Author(s).
- Published
- 2012
41. Spectrum handoff scheme with multiple attributes decision making for optimal network selection in cognitive radio networks
- Author
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Kumar, Krishan, Prakash, Arun, and Tripathi, Rajeev
- Published
- 2017
- Full Text
- View/download PDF
42. In-situ observation of the initiation of plasticity by nucleation of prismatic dislocation loops
- Author
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Lee, Subin, Vaid, Aviral, Im, Jiseong, Kim, Bongsoo, Prakash, Arun, Guénolé, Julien, Kiener, Daniel, Bitzek, Erik, and Oh, Sang Ho
- Published
- 2020
- Full Text
- View/download PDF
43. A novel hybrid medium access control protocol for inter-M2M communications
- Author
-
Verma, Pawan Kumar, Verma, Rajesh, Prakash, Arun, Tripathi, Rajeev, and Naik, Kshirasagar
- Published
- 2016
- Full Text
- View/download PDF
44. Machine-to-Machine (M2M) communications: A survey
- Author
-
Verma, Pawan Kumar, Verma, Rajesh, Prakash, Arun, Agrawal, Ashish, Naik, Kshirasagar, Tripathi, Rajeev, Alsabaan, Maazen, Khalifa, Tarek, Abdelkader, Tamer, and Abogharaf, Abdulhakim
- Published
- 2016
- Full Text
- View/download PDF
45. Spectrum handoff in cognitive radio networks: A classification and comprehensive survey
- Author
-
Kumar, Krishan, Prakash, Arun, and Tripathi, Rajeev
- Published
- 2016
- Full Text
- View/download PDF
46. Preparation, Spectroscopic Characterization, Theoretical Investigations, and In Vitro Anticancer Activity of Cd(II), Ni(II), Zn(II), and Cu(II) Complexes of 4(3H)-Quinazolinone-Derived Schiff Base
- Author
-
Ubale Panchsheela Ashok, Shiva Prasad Kollur, Nishad Anil, Bansode Prakash Arun, Sanjay Namdev Jadhav, Sanjay Sarsamkar, Vasant Baburao Helavi, Asha Srinivasan, Sandeep Kaulage, Ravindra Veerapur, Sarah Al-Rashed, Asad Syed, Joaquín Ortega-Castro, Juan Frau, Norma Flores-Holguín, and Daniel Glossman-Mitnik
- Subjects
3-quinolin-4(3H)-one ,metal complexes ,spectral studies ,chemical reactivity properties ,conceptual DFT ,Organic chemistry ,QD241-441 - Abstract
Herein, we report the synthesis and characterization of a new Schiff base ligand 3-[[(E)-(3-hydroxyphenyl)-methylidene]amino]-2-methyl-quinazolin-4(3H)-one (HAMQ) and its Cd(II), Ni(II), Zn(II), and Cu(II) complexes (C1–C4). The ligand HAMQ was synthesized by reacting 3-hydroxybenzaldehyde and 3-amino-2-methyl-4(3H)-quinazolinone in a 1:1 molar ratio. The structure of the ligand and its complexes (C1–C4) were evaluated using ultraviolet (UV)–visible (Vis) light spectroscopy, 1H-NMR, Fourier-transform infrared (FT-IR) spectroscopy, MS, elemental analysis, conductance data, and thermogravimetric analysis (TGA). The characterization results suggested that the bidentate ligand, HAMQ, coordinated to the metal center through the lactum oxygen and the azomethine nitrogen. Moreover, all the metal complexes were analyzed using powder X-ray diffraction studies, which revealed that all of them belong to a triclinic crystal system. The research was supplemented by density functional theory (DFT) studies on the IR and UV–Vis spectra, as well as the chemical reactivity of the HAMQ and its four metallic derivatives making use of conceptual density functional theory (CDFT) by means of KID (Koopmans in DFT) methodology. The synthesized complexes displayed significant in vitro anticancer activity against human cancer cell lines (HeLa and HCT-115).
- Published
- 2020
- Full Text
- View/download PDF
47. Ageing leads to reduced specificity of antimicrobial peptide responses in Drosophila melanogaster
- Author
-
Shit, Biswajit, primary, Prakash, Arun, additional, Sarkar, Saubhik, additional, Vale, Pedro F., additional, and Khan, Imroze, additional
- Published
- 2022
- Full Text
- View/download PDF
48. Variationally consistent coupling of non-matching discretizations for large deformation problems
- Author
-
Wang, Xiaowo, Prakash, Arun, Chen, Jiun-Shyan, and Taciroglu, Ertugrul
- Published
- 2017
- Full Text
- View/download PDF
49. Mechanisms of damage prevention, signalling, and repair impact disease tolerance
- Author
-
Prakash, Arun, Monteith, Katy, and Vale, Pedro
- Subjects
tissue damage repair ,enteric infection ,oral bacterial infection ,gut-epithelial immunity ,infection dose ,disease tolerance - Abstract
The insect gut is frequently exposed to pathogenic threats and must not only clear these potential infections, but also tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance. We investigated how well-described mechanisms that either prevent, signal, control, or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen Pseudomonas entomophila in transgenic lines of Drosophila melanogaster fruit flies affecting dcy (a major component of the peritrophic matrix), upd3 (a cytokine-like molecule), irc (a negative regulator of reactive oxygen species) and egfr1 (epithelial growth factor receptor). Flies lacking dcy experienced the highest mortality, while loss of function of either irc or upd3 reduced tolerance in both sexes. The disruption of egfr1 resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate P. entomophila infection, despite carrying greater microbe loads than males. Together, our findings provide evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sexual dimorphism in these mechanisms could generate sex differences in infection outcomes.
- Published
- 2022
50. Mechanisms of damage prevention, signalling and repair impact disease tolerance
- Author
-
Prakash, Arun, primary, Monteith, Katy M., additional, and Vale, Pedro F., additional
- Published
- 2022
- Full Text
- View/download PDF
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