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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. one sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. one specific inflammasome, the NoD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NoD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NoD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Discrete element modelling of the quasi-static uniaxial compression of individual infant formula agglomerates

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Particuology 2012年第5期10卷 523-531页

作者： kevin J.Hanley Catherine o'Sullivan Edmond P.Byrne kevin Cronin Department of Process and Chemical Engineering University College CorkCorkIreland Department of Civil and Environmental Engineering Skempton BuildingImperial College LondonLondon SW7 2AZ United Kingdom

Infant formula is usually produced in an agglomerated powder form. These agglomerates are subjected to many transient forces following their manufacture. These can be difficult to quantify experimentally because of their small magnitudes and short durations, Numerical models have the potential to address this gap in the experimental data. The objective of the research described here was to calibrate a discrete element model for these agglomerates using experimental data obtained for quasi-static loading, and to use this model to study the mechanics of the particle response in detail. The Taguchi method was previously proposed as a viable calibration approach for discrete element models. In this work, the method was assessed for calibration of the model parameters （e.g., bond stiffnesses and strengths） considering three responses： the force at failure, strain at failure and agglomerate stiffness. The Weibull moduli for the simulation results and the experimental data were almost identical following calibration and the 37% characteristic stresses were similar. An analysis of the energy terms in the model provided useful insight into the model response. The bond energy and the normal force exerted on the platens were strongly correlated, and bond breakage events coincided with the highest energy dissipation rates.

关键词： Discrete element modellingUniaxial compressionQuasi-static crushingSimulationGranular materialsTaguchi methods

Implementation of rotational resistance models＇ A critical appraisal

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Particuology 2017年第5期15卷 14-23页

作者： Xin Huang kevin J. Hanley Catherine o'Sullivan Chung-Yee Kwok a Department of Geotechnical Engineering Tongji University Shanghai 200092 China Key Laboratory of Geotechnical and Underground Engineering of Ministry of Education Tongji University Shanghai 200092 China Institute for Infrastructure and Environment School of Engineering The University of Edinburgh Edinburgh EH9 3JL United Kingdom Skempton Building Department of Civil and Environmental Engineering Imperial College London London SW72AZ United Kingdom Haking Wong Building Department of Civil and Environmental Engineering The University ofHong Kong Hong Kong China

Contact models that simulate rotational resistance at particle contacts have been proposed as a means to capture the effect of shape in DEM simulations. This contribution critically explores some key issues related to the implementation of rotational resistance models; these include the need for physically meaningful model parameters, the impact of the model on the overall numerical stability/critical time increment for the DEM model, model validation, and the assessment of model performance relative to real physical materials. The discussion is centred around a rotational resistance model that captures the resistance provided by interlocking asperities on the particle surface. An expression for the maximum permissible integration time step to ensure numerical stability is derived for DEM simulations when rotational resistance is incorporated. Analytical solutions for some single-contact scenarios are derived for model validation. The ability of this type of model to provide additional fundamental insight into granular material behaviour is demonstrated using particle-scale analysis of triaxial compression simulations to examine the roles that contact rollin~ and slidin~ have on the stability of stron：~ force chains.

关键词： Granular mediaParticle shapeDiscrete element methodRollingTwistingRotational resistance

Enhanced cortical bone expansion in Lgals3-deficient mice during aging

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Bone Research 2018年第1期6卷 95-106页

作者： kevin A.Maupin kevin Weaver Alexis Bergsma Cheryl Christie Zhendong A.Zhong Tao Yang Bart o.Williams Center for Cancer and Cell Biology Program for Skeletal Disease and Tumor Microenvironment Van Andel Research Institute

Imbalances between bone formation and bone resorption, which can occur due to aging or sex hormone deprivation, result in decreased bone mass and an increased risk of fracture. Previous studies have suggested that the β-galactoside binding lectin,galectin-3, is involved in bone remodeling. We compared bone parameters of mice having null alleles of the galectin-3 gene(Lgals3-Ko) with those of their wild-type littermates. Lgals3 deficiency increased cortical bone expansion at 36 weeks(wk) and preserved or enhanced bone mass in both male and female mutant mice. In addition, female Lgals3-Ko mice were protected from age-related loss of trabecular bone. Histomorphometry and ex vivo primary cell differentiation assays showed increased osteoblastogenesis with little-to-no effect on osteoclastogenesis, suggesting the increased bone mass phenotype is primarily due to increased anabolism. our study identifies galectin-3 as a negative regulator of bone formation and suggests that disruption of galectin-3 may be useful in preventing bone loss during aging.

关键词： Lgals3-Ko their wild-type Histomorphometry

Unfoldomics of prostate cancer： on the abundance and roles of intrinsically disordered proteins in prostate cancer

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Asian Journal of Andrology 2016年第5期18卷 662-672页

作者： kevin S Landau Insung Na Ryan o Schenck Vladimir N Uversky DepartmentofMolecularMedicine MorsaniCollegeofMedicineUniversityofSouthFloridaTampaFL33612USA USFHealthByrdAlzheimer'sResearchInstitute MorsaniCollegeofMedicineUniversityofSouthFloridaTampaFlorida33612USA LaboratoryofStructuralDynamics StabilityandFoldingofProteinsInstituteofCytologyRussianAcademyofSciencesStPetersburgRussia

Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.

关键词： intrinsical ly disordered proteins posttranslational mod ifications prostate cancer protein-protein interaction proteomics proteome unfoldome

Effect of sample size on the response of DEM samples with a realistic grading

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Particuology 2014年第4期12卷 107-115页

作者： Xin Huang kevin J.Hanley Catherine o'Sullivan Fiona C.Y.Kwok Skempton Building Department of Civil and Environmental EngineeringImperial College LondonLondon SW7 2AZUnited Kingdom Haking Wong Building Department of Civil EngineeringThe University of Hong Kong

This paper shows that for DEM simulations of triaxial tests using samples with a grading that is repre- sentative of a real soil, the sample size significantly influences the observed material response. Four DEM samples with identical initial states were produced： three cylindrical samples bounded by rigid wails and one bounded by a cubical periodic cell, When subjected to triaxial loading, the samples with rigid boundaries were more dilative, stiffer and reached a higher peak stress ratio than the sample enclosed by periodic boundaries. For the rigid-wall samples, dilatancy increased and stiffness decreased with increasing sample size, The periodic sample was effectively homogeneous, The void ratio increased and the contact density decreased close to the rigid walls, This heterogeneity reduced with increasing sample size. The positions of the critical state lines （CSLs） of the overall response in e-log p＇ space were sensitive to the sample size, although no difference was observed between their slopes. The critical states of the interior regions of the rigid-wall-bounded samples approached that of the homogeneous periodic sample with increasing sample size. The ultimate strength of the material at the critical state is independent of sample size.

关键词： Discrete element method Sample size Rigid boundary Periodic boundary Critical state

Interpretation of pipe-jacking and lubrication records for drives in silty soil

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Underground Space 2020年第3期5卷 199-209页

作者： kevin G.o’Dwyer Bryan A.McCabe Brian B.Sheil Civil Engineering College of Engineering and InformaticsNational University of IrelandGalwayIreland Department of Engineering Science University of OxfordUnited Kingdom

In recent years,there has been an increased resort to microtunnelling/pipe-jacking as a means of constructing underground conduits(for water,sewage,gas,and other utilities)to avoid on-street disruption in urban *** this paper,technical details of two 1200 mm internal diameter microtunnels in silty sand totalling over 550 m in length are *** average skin friction values are extremely low for both drives suggesting effective lubrication practice,differences in normalised bentonite volumes appear to be responsible for differences in skin *** or near full buoyancy of the pipeline has been demonstrated for the majority of the *** frictional stress increase after a stoppage is shown to depend on not only the stoppage duration but also on the normalised lubrication *** of data in the manner presented in the paper is an important means of assimilating experience of microtunnelling in different ground conditions.

关键词： Microtunnelling Pipe-jacking Skin friction Lubrication Pipe buoyancy Stoppages

A thermodynamic perspective on electrode poisoning in solid oxide fuel cells

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1449-1455页

作者： kevin Huang Department of Mechanical Engineering University of South CarolinaColumbiaUSA

A critical challenge to the commercialization of clean and high-efficiency solid oxide fuel cell(SoFC)technology is the insuf-ficient stack lifespan caused by a variety of degradation mechanisms,which are associated with cell components and chemical *** components related degradation refers to thermal/chemical/electrochemical deterioration of cell materials under operating conditions,whereas the latter regards impurities in feedstocks of oxidant(air)and reductant(fuel).This article provides a thermodynamic perspective on the understanding of the impurities-induced degradation mechanisms in *** discussion focuses on using thermodynamic ana-lysis to elucidate poisoning mechanisms in cathodes by impurity species such as Cr,Co_(2),H_(2)o,and So_(2) and in the anode by species such as S(or H_(2)S),Sio_(2),and P_(2)(or PH_(3)).The author hopes the presented fundamental insights can provide a theoretical foundation for search-ing for better technical solutions to address the critical degradation challenges.

关键词： impurities air fuel reaction activity

Mixed ion and electron transport theory and application in solid oxide conductors

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International Journal of Minerals,Metallurgy and Materials 2022年第4期29卷 870-875页

作者： kevin Huang Department of Mechanical engineering University of South CarolinaColumbiaSC 292201USA

Mixed ions and electron conductors(MIECs)are an important family of electrocatalysts for electrochemical devices,such as reversible solid oxide cells,rechargeable metal-air batteries,and oxygen transport *** ionic and electronic transports in these materials play a key role in electrocatalytic *** in-depth fundamental understanding of the transport phenomena is critically needed to develop better *** this brief review,we introduced generic ionic and electronic transport theory based on irreversible thermodynamics and applied it to practical oxide-based materials with oxygen vacancies and electrons/holes as the predominant *** oxide systems,namely Ceo_(2)-based and La Cro_(3)-based materials,are selected as case studies to illustrate the utility of the transport theory in predicting oxygen partial pressure distribution across MIECs,electrochemical electronic/ionic leakage currents,and the effects of external load current on the leakage currents.

关键词： irreversible thermodynamics diffusivity charge neutrality electrochemical potential electrostatic potential