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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

Testosterone and cardiovascular disease in men

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Asian Journal of Andrology 2012年第3期14卷 428-435,I0007页

作者： Paul D Morris kevin s Channer sheffield Teaching Hospital NHs Trust Sheffield S10 2JF UK

Despite regional variations in the prevalence of coronary artery disease （CAD）, men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ＇Perspectives＇ article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ＇cause＇ versus ＇effect＇ controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.

关键词： atherosclerosis chronic heart failure ischaemic heart disease replacement therapy testosterone

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

Model Change Active Learning in Graph-Based semi-supervised Learning

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Communications on Applied Mathematics and Computation 2024年第2期6卷 1270-1298页

作者： kevin s.Miller Andrea L.Bertozzi Department of Mathematics University of CaliforniaLos Angeles520 Portola PlazaLos AngelesCA 90095USA

Active learning in semi-supervised classification involves introducing additional labels for unlabelled data to improve the accuracy of the underlying classifier.A challenge is to identify which points to label to best improve performance while limiting the number of new labels."Model Change"active learning quantifies the resulting change incurred in the classifier by introducing the additional label(s).We pair this idea with graph-based semi-supervised learning(ssL)methods,that use the spectrum of the graph Laplacian matrix,which can be truncated to avoid prohibitively large computational and storage *** consider a family of convex loss functions for which the acquisition function can be efficiently approximated using the Laplace approximation of the posterior *** show a variety of multiclass examples that illustrate improved performance over prior state-of-art.

关键词： Active learning Graph-based methods semi-supervised learning(ssL) Graph Laplacian

Multistage Off-Line Permutation Packet Routing on a Mesh:An Approach with Elementary Mathematics

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Journal of Computer science & Technology 2009年第1期24卷 175-180页

作者： kevin Chiew school of Information systems Singapore Management University80 Stamford RoadSingapore 178902

Various methods have been proposed for off-line permutation packet routing on a mesh. One of the methods is known as multistage routing, in which the first stage is crucial. For the first stage of routing, the previous study normally converts it to a problem of graph theory and proves the existence of solutions. However, there is a lack of simple algorithms to the first stage of routing. This article presents an explicit and simple approach for the first stage of routing based on elementary mathematics.

关键词： permutation packet routing explicit algorithm

Expanding beyond canonical metabolism:Interfacing alternative elements,synthetic biology,and metabolic engineering

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synthetic and systems Biotechnology 2018年第1期3卷 20-33页

作者： kevin B.Reed Hal s.Alper McKetta Department of Chemical Engineering The University of Texas at Austin200E Dean Keeton St.Stop C0400AustinTX 78712USA Institute for Cellular and Molecular Biology The University of Texas at Austin2500 Speedway AvenueAustinTX 78712USA

Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable ***,most industrial applications have focused on only a small subset of elements from the periodic table,centered around carbon *** review aims to illustrate the expanse of chemical elements that can currently(and potentially)be integrated into useful products using cellular ***,we describe recent advances in expanding the cellular scope to include the halogens,selenium and the metalloids,and a variety of metal *** examples range from small molecules,heteroatom-linked uncommon elements,and natural products to biomining and nanotechnology ***,this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

关键词： Metabolic engineering synthetic biology Unnatural metabolism Halogenation Cellular factories Non-canonical elements

Daoism and the German Mission in Martin Heidegger's“The Thing”

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Frontiers of Philosophy in China 2019年第4期14卷 570-592页

作者： Mark kevin s.Cabural Division of Humanities Hong Kong University of Science and TechnologyHong KongChina

In this article,I examine Martin Heidegger’s 1950 lecture/essay“The Thing”(Das Ding)in two ***,as a piece influenced by chapter 11 of the *** second,as a postwar writing which can be interpreted vis-a-vis the Black Notebooks and his other *** are instances in“The Thing”which are analogous to his statements found in the Black Notebooks and his other writings which describe and clarify his controversial political *** brief,I suggest here that Heidegger’s articulation of the concept of wu 無 of chapter 11 of the Daodejing as the void of the jug in“The Thing”may potentially describe his controversial engagement with German National socialism as part of his response to the call for German ***,the fundamentality of the void of the jug is comparable to the exclusivity and exceptionality of the Germans in their mission;and the use of the void of the jug as outpouring is an interesting way to emphasize his disagreement with the regime by pointing out that his support to German National socialism is not to the extent of brutally annihilating the Jews.

关键词： Martin Heidegger Daodejing German mission nothing void emptiness

Interdependence of friction, wear, and noise: A review

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Friction 2021年第6期9卷 1319-1345页

作者： kevin LONTIN Muhammad KHAN Cranfield University MK430ALUK

Phenomena of friction,wear,and noise in mechanical contacts are particularly important in the field of tribomechanics but equally complex if one wants to represent their exact relationship with mathematical *** have been made to describe these phenomena with different approaches in *** efforts have been compiled in different reviews but most of them treated friction,wear mechanics,and acoustic noise ***,an in-depth review that provides a critical analysis on their interdependencies is still *** this review paper,the interdependencies of friction,wear,and noise are analysed in the mechanical contacts at asperitical *** origin of frictional noise,its dependencies on contact’s mechanical properties,and its performance under different wear conditions are critically reviewed.A discussion on the existing mathematical models of friction and wear is also provided in the last section that leads to uncover the gap in the existing *** review concludes that still a comprehensive analytical modelling approach is required to relate the interdependencies of friction,noise,and wear with mathematical expressions.

关键词： noise acoustic emission wear friction