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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason h.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi hou Andrew M.Intlekofer Richard M.higashi Teresa W.M.Fan Andrew N.Lane kevin h.eng Brahm h.Segal Elizabeth A.Repasky Kelvin P.Lee Scott h.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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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

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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands Department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

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high temperature deformation and recrystallization behavior of magnesium bicrystals with 90°<1010>and 90°<1120>tilt grain boundaries

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Journal of Magnesium and Alloys 2024年第2期12卷 625-638页

作者： kevin Bissa Talal Al-Samman Dmitri A.Molodov Institute of Physical Metallurgy and Materials Physics RWTH Aachen University52056 AachenGermany International Research Organization for Advanced Science and Technology(IROAST) Kumamoto UniversityKumamoto 860-8555Japan

The deformation mechanisms and dynamic recrystallization(DRX)behavior of specifically grown bicrystals with a symmetric 90°and 90°tilt grain boundary,respectively,were investigated under deformation in plane strain compression at 200℃and 400℃.The microstructures were analyzed by panoramic optical microscopy and large-area electron backscatter diffraction(EBSD)orientation *** analysis employed a meticulous approach utilizing hundreds of individual,small EBSD maps with a small step size that were stitched together to provide comprehensive access to orientation and misorientation data on a macroscopic *** slip primarily governed the early stages of deformation at the two temperatures,and the resulting shear induced lattice rotation around the transverse direction(TD)of the *** existence of the grain boundary gave rise to dislocation pile-up in its vicinity,leading to much larger TD-lattice rotations within the boundary region compared to the *** increasing temperature,the deformation was generally more uniform towards the bulk due to enhanced dislocation mobility and more uniform stress *** recrystallization at 200℃was initiated in{1011}-compression twins at strains of 40%and *** 400℃,DRX consumed the entire grain boundary region and gradually replaced the deformed microstructure with progressing *** recrystallized grains displayed characteristic orientations,such that their c-axes were perpendicular to the TD and additionally scattered between 0°and 60°from the loading *** recrystallized grains displayed mutual rotations of up to 30°around the c-axes of the initial grains,forming a discernible basal fiber texture component,prominently visible in the{1120}pole *** is noteworthy that the deformation and DRX behaviors of the two analyzed bicrystals exhibited marginal variations in response to strain and deformation temperature.

关键词： Elevated deformation temperatures Plain strain compression Magnesium bicrystals Panorama EBSD Dynamic Recrystallization

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Injury and protection of spiral ganglion neurons

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Chinese Medical Journal 2024年第6期137卷 651-656页

作者： Beilei Duan kevin A.Peng Line Wang Department of Otorhinolaryngology Head and Neck SurgeryBeijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Neurotology House ClinicLos AngelesCA 90017USA

Cochlear spiral ganglion neurons(SGNs)are bipolar ganglion cells and are the first neurons in the auditory transduction *** transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound *** to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate,making treatment of sensorineural hearing loss(SNhL)arising from SGN injury *** exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors(NTFs),aging,and presence of other factors,SGNs can be irreversibly damaged,resulting in *** has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion *** this paper,we summarized the present knowledge regarding injury,protection,and regeneration of SGNs.

关键词： Spiral ganglion Injury Protection Auditory hair cell Ototoxic drugs Aminoglycosides Presbycusis

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Orthogonal polynomial expansions for the valuation ofoptions under the stochastic volatility models with stochastic correlation

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Journal of Management Science and engineering 2024年第2期9卷 239-253页

作者： kevin Z.Tong Department of Mathematics and Statistics University of Ottawa585 King EdwardOttawaOntarioK1N 6N5Canada

This work provides a new method for pricing options under the generalized stochastic volatility models with Jacobi stochastic *** method is based on the observation that the generalized models belong to the class of polynomial diffusions and therefore the option prices can be efficiently computed via orthogonal polynomial *** take the heston and Schöbel-Zhu models with stochastic correlation as two specific examples and are able to derive the analytical formulas for the option *** also illustrate the accuracy of the proposed method through a number of numerical experiments.

关键词： Orthogonal polynomial expansions Polynomial diffusions Stochastic correlation Jacobi process Stochastic volatility

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Neurolithography:Lithography as an enabling technology in neurology and neuroscience

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Medicine in Novel Technology and Devices 2024年第2期22卷 15-18页

作者： kevin Zhai Department of Medical Education Weill Cornell Medicine-QatarP.O.Box 24144DohaQatar

Modern lithography,which enables the fabrication of complex structures in biomedical devices with exceptional precision,is a potentially transformative force in the neural *** such as photolithography,electron beam lithography,and soft lithography have been utilized to produce devices that guide neuronal growth and differentiation and measure electrophysiological signals at the single-cell *** the clinical sphere,lithography plays a role in the manufacturing of devices for deep brain stimulation,brain-computer interface,and ***,we briefly review the applications of lithography in basic and translational neuroscience and clinical neurology,with an eye toward future advancement.

关键词： Lithography Neurolithography Semiconductors Microfluidics Neural devices

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Numerical Study of Semidiscrete Penalty Approach for Stabilizing Boussinesq System with Localized Feedback Control

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Annals of Applied Mathematics 2024年第2期40卷 191-218页

作者： Mejdi Azaiez kevin Le Balc'h Universite de Bordeaux Bordeaux-INPI2M UMR5295F-33400TalenceFrance Inria Sorbonne UniversiteUniversite de ParisCNRSLaboratoire Jacques-Louis LionsParisFrance

We investigate the numerical approximation for stabilizing the semidiscrete linearized Boussinesq system around an unstable stationary *** is attained through internal feedback controls applied to the velocity and temperature equations,localized within an arbitrary open *** study follows the framework presented in[14],considering the continuous linearized Boussinesq *** primary objective is to explore the penalizationbased approximation of the free divergence condition in the semidiscrete case and provide a numerical validation of these results in a two-dimensional setting.

关键词： Boussinesq system penalty method stabilization feedback control

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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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Failure characterization of fully grouted rock bolts under triaxial testing

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Journal of Rock Mechanics and Geotechnical engineering 2024年第3期16卷 778-789页

作者： hadi Nourizadeh Ali Mirzaghorbanali Mehdi Serati Elamin Mutaz kevin McDougall Naj Aziz Centre for Future Materials(CFM) School of EngineeringUniversity of Southern QueenslandToowoombaQLD4350Australia School of engineering University of Southern QueenslandSpringfield CentralQLD4300Australia School of Civil engineering University of QueenslandSt LuciaQLD4072Australia School of Surveying and Build Environment University of Southern QueenslandToowoombaQLD4350Australia School of Civil Mining&Environmental EngineeringUniversity of WollongongWollongongNSW2500Australia

Confining stresses serve as a pivotal determinant in shaping the behavior of grouted rock ***,prior investigations have oversimplified the three-dimensional stress state,primarily assuming hydrostatic stress *** these conditions,it is assumed that the intermediate principal stress(σ_(2))equals the minimum principal stress(σ_(3)).This assumption overlooks the potential variations in magnitudes of in situ stress conditions along all three directions near an underground opening where a rock bolt is *** this study,a series of push tests was meticulously conducted under triaxial *** tests involved applying non-uniform confining stresses(σ_(2)≠σ_(3))to cubic specimens,aiming to unveil the previously overlooked influence of intermediate principal stresses on the strength properties of rock *** results show that as the confining stresses increase from zero to higher levels,the pre-failure behavior changes from linear to nonlinear forms,resulting in an increase in initial stiffness from 2.08 kN/mm to 32.51 kN/*** load-displacement curves further illuminate distinct post-failure behavior at elevated levels of confining stresses,characterized by enhanced ***,the peak load capacity ranged from 27.9 kN to 46.5 kN as confining stresses advanced from σ_(2)=σ_(3)=0 to σ_(2)=20 MPa and σ_(3)=10 ***,the outcomes highlight an influence of confining stress on the lateral deformation of *** levels of confinement prompt overall dilation in lateral deformation,while higher confinements maintain a state of ***,diverse failure modes have been identified,intricately tied to the arrangement of confining *** confinements tend to induce a splitting mode of failure,whereas higher loads bring about a shift towards a pure interfacial shear-off and shear-crushed failure mechanism.

关键词： Rock bolts Bolt-grout interface Bond strength Push test Triaxial tests

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