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Mechanism-driven strategies for prevention of rheumatoid arthritis

Rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： V.Michael Holers Kristine A.Kuhn M.Kristen demoruelle Jill M.Norris Gary S.Firestein Eddie A.James William H.Robinson Jane H.Buckner kevin d.deane division of Rheumatology University of Colorado School of MedicineAuroraColoradoUSA department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA division of Rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research Institute SeattleWashingtonUSA division of Immunology and Rheumatology Stanford UniversityStanfordCaliforniaUSA department of Medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

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dynamics of Advantageous Mutant Spread in Spatial death-Birth and Birth-death Moran Models

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Communications on Applied Mathematics and Computation 2024年第1期6卷 576-604页

作者： Jasmine Foo Einar Bjarki Gunnarsson kevin Leder david Sivakoff School of Mathematics University of MinnesotaTwin CitiesMN55455USA department of Industrial and Systems Engineering University of MinnesotaTwin CitiesMN55455USA departments of Statistics and Mathematics The Ohio State UniversityColumbusOH43210USA

The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.

关键词： Spatial death-birth models Spatial birth-death models Spatial evolutionary models Spatial cancer models Evolutionary graph theory Stochastic processes Biased voter model dual process Fixation probability Shape theorem

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Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

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Neural Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Golam Jiamei Hou kevin K.W.Wang Floyd J.Thompson Prodip Bose Brain Rehabilitation Research Center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA department of Anesthesiology College of MedicineUniversity of FloridaGainesvilleFLUSA department of Emergency Medicine University of FloridaGainesvilleFLUSA department of Neuroscience University of FloridaGainesvilleFLUSA department of Neurology University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

关键词： balance blood flow cardiovascular system central nervous system epinephrine ischemic damage lumbar spinal cord muscle tone repeated blast spasticity traumatic brain injury

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Asbestos Exposure during Gasket Removal from Aircraft Engine

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Occupational diseases and Environmental Medicine 2024年第2期12卷 59-67页

作者： Charles L. Blake kevin M. Guth Raymond d. Harbison Apex Companies Marietta USA Center for Environmental and Occupational Risk Analysis and Management College of Public Health University of South Florida Tampa USA

We have previously evaluated asbestos exposure associated with various maintenance procedures on light aircraft. The purpose of this study was to evaluate asbestos exposure during engine maintenance on light aircraft. This test was designed to evaluate the potential for asbestos exposure to mechanics and others who remove asbestos-containing engine gaskets from reciprocating style aircraft engines. Utilized in this test was an air cooled, horizontally opposed, aviation gasoline burning engine, assembled during 1986 and operated intermittently up into 2015, having accumulated 1680 hours run time. Nearly 75% of the asbestos-containing gaskets installed during 1986 were still in place at the time of testing. Chrysotile asbestos contents of such gaskets ranged from 55% to 60% by area, for those of sheet style and 5% by area, for the spiral wound metal/asbestos style. despite the levels of effort required to effect gasket removals, the professional aircraft mechanic was not exposed to airborne asbestos fibers at the lower limits of sampling and analytical detection achieved;all of which were substantially less than the current Occupational Safety and Health Administration Permissible Exposure Limits for asbestos. The results of this testing indicate an absence of gasket related asbestos exposure risk to mechanics who work with light aircraft engines, including those having asbestos-containing gaskets. These results are consistent with the findings of Mlyarek and Van Orden who studied the asbestos exposure risk occasioned during overhaul of larger radial style reciprocating aircraft engines [1].

关键词： Asbestos Exposure Gaskets Aircraft Engine Friction Materials

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HISP-1 Inhibits HSV-1 Infection in Cultured Vero Cells

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Advances in Bioscience and Biotechnology 2024年第4期15卷 269-288页

作者： Sandra d. Adams kevin T. Bilyk Modukuri V. Ramani Gottumukkala V. Subbaraju department of Biology Montclair State University Montclair USA department of Chemistry Andhara University Visakhapatnam India

Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability, percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein d (gd). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.

关键词： Hispolon Herpes Simplex Virus-1 Antiviral Curcumin

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Interfacial engineering through lead binding using crown ethers in perovskite solar cells

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Journal of Energy Chemistry 2024年第5期92卷 263-270页

作者： Sun-Ju Kim YeonJu Kim Ramesh Kumar Chitumalla Gayoung Ham Thanh-danh Nguyen Joonkyung Jang Hyojung Cha Jovana Milić Jun-Ho Yum kevin Sivula Ji-Youn Seo department of Nano Fusion Technology Pusan National UniversityBusan 46241Republic of Korea Laboratory for Molecular Engineering of Optoelectronic Nanomaterials Institute of Chemical Sciences and EngineeringÉcole Polytechnique Fédérale de Lausanne(EPFL)1015 LausanneSwitzerland department of Energy Convergence and Climate Change Kyungpook National UniversityDaegu 41566Republic of Korea department of Hydrogen and Renewable Energy Kyungpook National UniversityDaegu 41566Republic of Korea Adolphe Merkle Institute University of FribourgCH-1700 FribourgSwitzerland

In the domain of perovskite solar cells(PSCs),the imperative to reconcile impressive photovoltaic performance with lead-related issue and environmental stability has driven innovative solutions.This study pioneers an approach that not only rectifies lead leakage but also places paramount importance on the attainment of rigorous interfacial passivation.Crown ethers,notably benzo-18-crown-6-ether(B18C6),were strategically integrated at the perovskite-hole transport material interface.Crown ethers exhibit a dual role:efficiently sequestering and immobilizing Pb^(2+)ions through host-guest complexation and simultaneously establishing a robust interfacial passivation layer.Selected crown ether candidates,guided by density functional theory(dFT)calculations,demonstrated proficiency in binding Pb2+ions and optimizing interfacial energetics.Photovoltaic devices incorporating these materials achieved exceptional power conversion efficiency(PCE),notably 21.7%for B18C6,underscoring their efficacy in lead binding and interfacial passivation.Analytical techniques,including time-of-flight secondary ion mass spectrometry(ToF-SIMS),ultraviolet photoelectron spectroscopy(UPS),time-resolved photoluminescence(TRPL),and transient absorption spectroscopy(TAS),unequivocally affirmed Pb^(2+)ion capture and suppression of non-radiative recombination.Notably,these PSCs maintained efficiency even after enduring 300 h of exposure to 85%relative humidity.This research underscores the transformative potential of crown ethers,simultaneously addressing lead binding and stringent interfacial passivation for sustainable PSCs poised to commercialize and advance renewable energy applications.

关键词： Perovskite solar cells Interfacial passivation Crown ether materials Stability

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Tensorial tomographic Fourier ptychography with applications to muscle tissue imaging

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Advanced Photonics 2024年第2期6卷 50-60页

作者： Shiqi Xu Xi Yang Paul Ritter Xiang dai Kyung Chul Lee Lucas Kreiss kevin C.Zhou Kanghyun Kim Amey Chaware Jadee Neff Carolyn Glass Seung Ah Lee Oliver Friedrich Roarke Horstmeyer duke University DurhamNorth CarolinaUnited States Friedrich-Alexander University ErlangenGermany UC San diego La JollaCaliforniaUnited States Yonsei University SeoulRepublic of Korea UC Berkeley BerkeleyCaliforniaUnited States duke University Medical Center DurhamNorth CarolinaUnited States

We report tensorial tomographic Fourier ptychography(T^(2)oFu),a nonscanning label-free tomographic microscopy method for simultaneous imaging of quantitative phase and anisotropic specimen information in 3d.Built upon Fourier ptychography,a quantitative phase imaging technique,T^(2)oFu additionally highlights the vectorial nature of light.The imaging setup consists of a standard microscope equipped with an LEd matrix,a polarization generator,and a polarization-sensitive camera.Permittivity tensors of anisotropic samples are computationally recovered from polarized intensity measurements across three dimensions.We demonstrate T^(2)oFu’s efficiency through volumetric reconstructions of refractive index,birefringence,and orientation for various validation samples,as well as tissue samples from muscle fibers and diseased heart tissue.Our reconstructions of healthy muscle fibers reveal their 3d fine-filament structures with consistent orientations.Additionally,we demonstrate reconstructions of a heart tissue sample that carries important polarization information for detecting cardiac amyloidosis.

关键词： computational imaging three-dimensional imaging phase retrieval microscopy polarization-sensitive imaging labelfree imaging

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dynamics of self-hybridized exciton–polaritons in 2d halide perovskites

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Light(Science & Applications) 2024年第1期13卷 13-22页

作者： Surendra B.Anantharaman Jason Lynch Christopher E.Stevens Christopher Munley Chentao Li Jin Hou Hao Zhang Andrew Torma Thomas darlington Francis Coen kevin Li Arka Majumdar PJames Schuck Aditya Mohite Hayk Harutyunyan Joshua R.Hendrickson deep Jariwala department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPA19104USA KBR Inc. BeavercreekOH45431USA Air Force Research Laboratory Sensors DirectorateWright-Patterson Air Force BaseOH45433USA department of Physics University of WashingtonSeattleWA98195USA department of Physics Emory UniversityAtlantaGA30322USA department of Chemical and Biomolecular Engineering Rice UniversityHoustonTX77005USA department of Materials Science and Nanoengineering Rice UniversityHoustonTX77005USA Applied Physics Program Smalley‐Curl InstituteRice UniversityHoustonTX77005USA department of Mechanical Engineering Columbia UniversityNew YorkNY10027USA department of Electrical and Computer Engineering University of WashingtonSeattleWA98195USA

Excitons,bound electron–hole pairs,in two-dimensional hybrid organic inorganic perovskites(2d HOIPs)are capable of forming hybrid light-matter states known as exciton-polaritons(E–Ps)when the excitonic medium is confined in an optical cavity.In the case of 2d HOIPs,they can self-hybridize into E–Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the excitons.However,the fundamental properties of these self-hybridized E–Ps in 2d HOIPs,including their role in ultrafast energy and/or charge transfer at interfaces,remain unclear.Here,we demonstrate that>0.5µm thick 2d HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E–P modes.These E–Ps have high Q factors(>100)and modulate the optical dispersion for the crystal to enhance sub-gap absorption and emission.Through varying excitation energy and ultrafast measurements,we also confirm energy transfer from higher energy E–Ps to lower energy E–Ps.Finally,we also demonstrate that E–Ps are capable of charge transport and transfer at interfaces.Our findings provide new insights into charge and energy transfer in E–Ps opening new opportunities towards their manipulation for polaritonic devices.

关键词： charge polar excitation

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Morphological Characterization of Arbuscular Mycorrhizal Fungi Associated with the Rhizosphere According to the Age of Xanthosoma sagittifolium L. Schott Plants in the Field

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American Journal of Plant Sciences 2024年第3期15卷 161-179页

作者： Audrey Maguy Bengono Nyimiebolo Astride Carole djeuani Hermann désiré Mbouobda Antoine Marie kevin Tiki Theresa Akinimbom Moma diobe Motassy Manuela Samuel Brice Adounga Christophe Fendju Pangueko Jones Nshanji Issofa Nguetrapouna Rose Theophine derricka djem Moutamal A. Ziem Amang Amang Nicolas Niemenak Laboratory of Plant Physiology Department of Biological Sciences Higher Teacher Training College (HTTC) University of Yaoundé I Yaoundé Cameroon department of Plant Biology Faculty of Sciences University of Yaoundé I Yaoundé Cameroon department of Biology Higher Teacher Training College Bambili (HTTC) The University of Bamenda Bamenda Cameroon departments of Microbiology Faculty of Science University of Yaoundé 1 Yaoundé Cameroon

The objective of this work was to carry out a morphological characterization of arbuscular mycorrhizal fungi in the rhizosphere of Xanthosoma sagittifolium L. Schott plants. The plant material used was the white and red cultivars of X. sagittifolium, belonging to age intervals of 3 - 6, 6 - 9, and 9 - 12 months. Three harvest sites were chosen in the Central Region of Cameroon. In each site, soil from the rhizosphere and plant roots was collected in a randomized manner. In the field, the agronomic parameters were evaluated. The physicochemical characteristics of the soils, the mycorrhization index, and the morphological characterization of the mycorrhizal types of each site were carried out. The results obtained show that the agronomic growth parameters varied significantly using the Student Newman and Keuls Test depending on the harvest sites. The soils’ pH in all sites was acidic and ranged between 4.6 and 5.8. The Nkometou site has a loamy texture while the Olembe and Soa sites have loam-clay-sandy and loam-clay textures respectively. The highest mycorrhization frequencies appeared at the Nkometou site, with 75 and 87.33% of the white and red cultivars plant roots at 6 - 9 and 3 - 6 months. The relative abundance of AMF arbuscular mycorrhizal fungal spores in the rhizosphere of X. sagittifolium plants varied with age and cultivar. There were 673 spores between 9 - 12 months in Nkometou in the red cultivar. Six AMF genera were identified in all the different soils collected: Acaulospora sp., Funneliformis sp., Gigaspora sp., Glomus sp., Scutellospora sp., and Septoglomus sp. The genus Glomus sp. was the most present at all age intervals in both cultivars.

关键词： Xanthosoma sagittifolium L. Schott Rhizosphere Harvest Site Arbuscular Mycorrhizal Fungi diversity

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Rapid Evaluation and Response to Impacts on Critical End-Use Loads Following Natural Hazard-driven Power Outages:A Modular and Responsive Geospatial Technology

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International Journal of disaster Risk Science 2022年第3期13卷 415-434页

作者： Patrick d.Royer Wei du kevin Schneider Energy and Environment Pacific Northwest National LaboratoryRichlandWA99352USA

The disparate nature of data for electric power utilities complicates the emergency recovery and response process.The reduced efficiency of response to natural hazards and disasters can extend the time that electrical service is not available for critical end-use loads,and in extreme events,leave the public without power for extended periods.This article presents a methodology for the development of a semantic data model for power systems and the integration of electrical grid topology,population,and electric distribution line reliability indices into a unified,cloud-based,serverless framework that supports power system operations in response to extreme events.An iterative and pragmatic approach to working with large and disparate datasets of different formats and types resulted in improved application runtime and efficiency,which is important to consider in real time decision-making processes during hurricanes and similar catastrophic events.This technology was developed initially for Puerto Rico,following extreme hurricane and earthquake events in 2017 and 2020,but is applicable to utilities around the world.Given the highly abstract and modular design approach,this technology is equally applicable to any geographic region and similar natural hazard events.In addition to a review of the requirements,development,and deployment of this framework,technical aspects related to application performance and response time are highlighted.

关键词： Electrical grid Hurricane response Puerto Rico Resilience and geospatial technology Software applications

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