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Single-cell Analysis of CAR-T Cell Activation Reveals A Mixed T_H1/T_H2 Response Independent of Differentiation

Genomics, Proteomics & Bioinformatics 2019年第2期17卷 129-139页

作者： Iva Xhangolli Burak dura GeeHee Lee Dongjoo Kim Yang Xiao Rong fan Department of Biomedical Engineering Yale University New Haven CT 06520 USA Yale Cancer Center Yale School of Medicine New Haven CT 06520 USA Yale Stem Cell Center Yale School of Medicine New Haven CT 06520

The activation mechanism of chimeric antigen receptor (CAR)-engineered T cells may differ substantially from T cells carrying native T cell receptor,but this difference remains poorly understood. We present the first comprehensive portrait of single-cell level transcriptional and cyto-kine signatures of anti-CD19/4-1BB/CD28/CD3ζ CAR-T cells upon antigen-specific stimulation. Both CD4+helper T (TH) cells and CD8+cytotoxic CAR-T cells are equally effective in directly killing target tumor cells and their cytotoxic activity is associated with the elevation of a range of TH1 and TH2 signature cytokines,e.g.,interferon γ,tumor necrotic factor α,interleukin 5 (IL5),and IL13,as confirmed by the expression of master transcription factor genes TBX21 and GATA3. However,rather than conforming to stringent TH1 or TH2 subtypes,single-cell analysis reveals that the predominant response is a highly mixed TH1/TH2 function in the same cell. The reg-ulatory T cell activity,although observed in a small fraction of activated cells,emerges from this hybrid TH1/TH2 population. Granulocyte-macrophage colony stimulating factor (GM-CSf) is pro-duced from the majority of cells regardless of the polarization states,further contrasting CAR-T to classic T cells. Surprisingly,the cytokine response is minimally associated with differentiation status,although all major differentiation subsets such as na?ve,central memory,effector memory,and effector are detected. All these suggest that the activation of CAR-engineered T cells is a canon-ical process that leads to a highly mixed response combining both type 1 and type 2 cytokines together with GM-CSf,supporting the notion that polyfunctional CAR-T cells correlate with objective response of patients in clinical trials. This work provides new insights into the mechanism of CAR activation and implies the necessity for cellular function assays to characterize the quality of CAR-T infusion products and monitor therapeutic responses in patients.

关键词： Single-cell transcriptomics Single-cell proteomics CAR-T T cell activation

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Merging bound states in the continuum in an open acoustic resonator

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 124-131页

作者： Lujun Huang Bin Jia Artem S.Pilipchuk Sibo Huang Chen Shen Almas f.Sadreev Yong Li Andrey E.Miroshnichenko School of Physics and Electronic Sciences East China Normal University Institute of Acoustics Tongji University L.V.Kirensky Institute of Physics Department of Mechanical Engineering Rowan University School of Engineering and Technology University of New South Wales at Canberra

Bound states in the continuum （BICs） are perfectly localized resonances despite embedding in the continuum ***,an isolated BIC is very sensitive to the structure ***,we report merging acoustic BICs in a single open resonator,robust against the structure *** find that both symmetry-protected BIC and friedrich-Wintgen BIC are sustained in a single coupled waveguide-resonator *** varying the height and length of the resonator,these two BICs move toward each other and merge into a single one at a critical *** to an individual BIC,the merged BIC is robust against fabrication error because its Q-factor is proportional to ΔL-4,whereΔL embodies the structure *** essence of this extraordinary phenomenon is perfectly explained by the two-and three-level approximations of the effective nonHermitian ***,we present direct experimental demonstrations of the moving and merging of BICs in a coupled 3D waveguide-resonator,which are evidenced by the vanishing of the linewidth of fano resonance in the transmission *** results may find exciting applications in designing high-quality acoustic sources,sensors and filters.

关键词： acoustic resonances bound state in the continuum high-Q resonances

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Determination of Nematicidal Effects of Some Biopesticides against Root-Knot Nematode （Meloidogyne incognita） on Kiwifruit

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Journal of Agricultural Science and Technology(A) 2017年第8期7卷 546-551页

作者： Ilker Kepenekci Onur dura Sami dura Department of Plant Protection Faculty of Agriculture Gaziosmanpasa University Tashciftlik Tokat 60250 Turkey Atatiirk Central Horticultural Research Institute Merkez Yalova 77100 Turkey ROTAM Lifesciences Kimyasal Tartm Tic. Ltd. Sti Pasaport lzmir 35210 Turkey

The aim of this study was to determine the nematicidal effects of some biopesticides againist root-knot nematodes （RKNs）（Meloidogyne incognita） on Bruno type kiwifruit seedlings. Research was conducted in the Atattirk Central Horticultural Research Institute （ACHRI, Yalova, Turkey） greenhouse during 2013-2014. Biopesticides observed in this study were： sesame oil （Devalone EC）, castor oil （Ricinus communis）, Myrothecium verrucaria （M. verrucaria strain AARC-0255, Inferno Df）, Glomus spp. （Endomycorrhizal fungi, Endo Roots Soluble SP） and Paecilomyces lilacinus （Entomopathogenic fungi, P. lilacinus strain PL1, Bionematon SL）. Nematicide Nemacur EC 400 （fenamiphos） was used as treated control （TC） and trials were set up as randomized parcel design （RPD） with seven characters and 10 replicates. Reproduction ratio was determined according to scale values in trial applications and second stage juvenile （J2） populations of M. incognita in soil. The results showed that the best nematicidal effects against RKNs were determined in castor oil （77.92% in 2013 and 73.61% in 2014） and P. lilacinus （61.03% in 2013 and 55.55% in 2014）.

关键词： Root-knot nematodes Meloidogyne incognita sesame oil castor oil Myrothecium verrucaria Glomus Paecilomyceslilacinus kiwifruit.

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DAMAGE TOLERANCE AND fATIGUE LIfE ESTIMATION fOR PIPE/ROD BAR STRUCTURE

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Transactions of Nanjing University of Aeronautics and Astronautics 2011年第2期28卷 169-175页

作者： dura Hari Bahadur 吴铁鹰吴志功南京航空航天大学能源与动力学院

The damage tolerance for pipe/rod bar in the auxiliary power units （APUs） support system is studied. The main objective is to study whether planes can safely land when the fatigue crack appears on the bar. firstly, the stress intensity factors （K~） of two bar structures are computed, and the iso-stress intensity factor （iso-Kl） model is presented. The model uses the finite element model （fEM） instead of the parameters of material to com- pute the crack propagation. Then, the general relations between Kt vs crack size are obtained for different mate- rials, inner to outer diameter ratios （D^n/Dout） and external crack propagation angles （0）. finally, the fEM anal- ysis results are input to the ANSYS parametric design language（ANSYS-APDL） software. And the fatigue life of damaged bar is estimated under the condition of loading spectrum.

关键词： fatigue crack propagation circumferential crack stress intensity factor pipe/rod bar

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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow Matthew f.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Leveraging ROTI map derived from Indonesian GNSS receiver network for advancing study of Equatorial Plasma Bubble in Southeast/East Asia

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Earth and Planetary Physics 2025年第1期9卷 101-116页

作者： Prayitno Abadi Ihsan N.Muafiry Teguh N.Pratama Angga Y.Putra Suraina Gatot H.Pramono Sidik T.Wibowo febrylian f.Chabibi Umar A.Ahmad Wildan P.Tresna Asnawi Research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia School of Electrical Engineering Telkom UniversityBandungIndonesia Directorate of Laboratory Management facilities and Science and Technology Park Indonesian National Research and Innovation Agency(BRIN)PontianakIndonesia Geophysics Laboratory Master Program in PhysicsUniversitas Gadjah Mada(UGM)YogyakartaIndonesia Research Center for Space Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia Research Center for Photonics Indonesian National Research and Innovation Agency(BRIN)Tangerang SelatanIndonesia Department of Earth and Planetary Sciences Hokkaido UniversitySapporoJapan

This paper highlights the crucial role of Indonesia’s GNSS receiver network in advancing Equatorial Plasma Bubble(EPB)studies in Southeast and East Asia,as ionospheric irregularities within EPB can disrupt GNSS signals and degrade positioning *** by the Indonesian Geospatial Information Agency(BIG),the Indonesia Continuously Operating Reference Station(Ina-CORS)network comprises over 300 GNSS receivers spanning equatorial to southern low-latitude ***-CORS is uniquely situated to monitor EPB generation,zonal drift,and dissipation across Southeast *** provide a practical tool for EPB research,by sharing two-dimensional rate of Total Electron Content(TEC)change index(ROTI)derived from this *** generate ROTI maps with a 10-minute resolution,and samples from May 2024 are publicly available for further scientific *** preliminary findings from the ROTI maps of Ina-CORS are ***,the Ina-CORS ROTI maps reveal that the irregularities within a broader EPB structure persist longer,increasing the potential for these irregularities to migrate farther ***,we demonstrate that combined ROTI maps from Ina-CORS and GNSS receivers in East Asia and Australia can be used to monitor the development of ionospheric irregularities in Southeast and East *** have demonstrated the combined ROTI maps to capture the development of ionospheric irregularities in the Southeast/East Asian sector during the G5 Geomagnetic Storm on May 11,*** observed simultaneous ionospheric irregularities in Japan and Australia,respectively propagating northwestward and southwestward,before midnight,whereas Southeast Asia’s equatorial and low-latitude regions exhibited irregularities *** sharing ROTI maps from Indonesia and integrating them with regional GNSS networks,researchers can conduct comprehensive EPB studies,enhancing the understanding of EPB behavior across Southeast and East Asia and contributing significantly to ionosphe

关键词： Equatorial Plasma Bubble(EPB) GNSS receivers’network Indonesia Continuously Operating Reference Station(Ina-CORS) ionospheric map Rate of TEC change index(ROTI)map

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friedrich Ackermann’s scientific research program

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Geo-Spatial Information Science 2023年第2期26卷 141-150页

作者： Wolfgang förstner Department of Photogrammetry UniversityBonnGermany

We sketch friedrich Ackermann’s research program following the concept of Imre Lakatos,with some historical key developments in the theory and application of aerotriangulation and image *** research program,with its core being statistical estimation theory,has decisively influenced photogrammetry since the 60s,is still fully alive,and a challenge for today’s methods of image *** describe(1)Lakatos’concept of a scientific research program,with its negative and positive heuristics and(2)Ackermann’s research program,clearly made explicit in his PhD,with its mathematical model,the ability to predict theoretical precision and reliability,the potential of analyzing rigorous and approximate method,and the role of *** development of aerotriangulation,later augmented by image matching techniques,is closely connected to Ackermann’s successful attempts to integrate basic research and practical applications.

关键词： friedrich Ackermann scientific research program aerotriangulation image matching role of theory and application

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Acoustic radiation force and torque on a lossless eccentric layered fluid cylinder

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Chinese Physics B 2020年第11期29卷 140-145页

作者： f G Mitri Santa fe NM 87508USA

Exact analytical equations and computations for the longitudinal and transverse acoustic radiation force and axial torque components for a lossless eccentric liquid cylinder submerged in a nonviscous fluid and insonified by plane waves progressive waves(of arbitrary incidence in the polar plane)are established and computed *** modal matching method and the translational addition theorem in cylindrical coordinates are used to derive exact mathematical expressions applicable to any inner and outer cylinder sizes without any approximations,and taking into account the interaction effects between the waves propagating in the layer and those scattered from the cylindrical *** results show that longitudinal and transverse radiation force components arise,in addition to the emergence of an axial radiation torque component acting on the non-absorptive compound cylinder due to geometrical asymmetry as the eccentricity *** computations demonstrate that the axial torque component,which arises due to a geometrical asymmetry,can be positive(causing counterclockwise rotation in the polar plane),negative(clockwise rotation)or neutral(rotation cancellation)depending on the size parameter of the cylinder and the amount of ***,verification and validation of the results have been accomplished from the standpoint of energy conservation law applied to scattering,and based on the reciprocity theorem.

关键词： acoustic radiation force acoustic radiation torque non-viscous liquid eccentric cylinder

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Operational feasibility study of stagnation pressure reaction control for a mid-caliber non-spinning projectile

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Defence Technology（防务技术） 2023年第6期24卷 109-121页

作者： f.Bouquet The Netherlands Organisation for Applied Scientific Research Oude Waalsdorperweg 632597 AK Den Haagthe Netherlands

Controlled,guided munitions can reduce dispersion in the shot,while providing the capability of engaging both stationary and maneuvering *** Netherlands Organisation for Applied Scientific Research has developed a fin-less control technology called Stagnation Pressure Reaction Control(SPRC)that takes stagnation pressure air and directs it sideways to control non-spinning *** a previous study,this technology was demonstrated at Mach 2 wind-tunnel conditions to achieve up to 1.5°controllable angle of incidence for a non-spinning,aerodynamically unstable projectile-like test *** an operational scenario,the decelerating projectile will experience a decline in control force while the simultaneous forward shift of the center of pressure increases the need for control ***,angles of incidence exceeding 1.5°will be experienced under realistic flight conditions,especially against maneuvering *** work addresses these challenges and presents an operational feasibility study for a practical application of SPRC in a non-spinning mid-caliber gun-launched projectile,using experiment data on control latency and force of the earlier *** illustrates the combined effect of the control-and stability dynamics and underlines the potential of an SPRC projectile as a precisionoperation *** research revealed that SPRC technology can stabilize and control the hypothesized projectile in a direct fire scenario against stationary and maneuvering targets.

关键词： Supersonic projectile feasibility study Ram air Stagnation pressure reaction control Simulation Attitude control

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Radiation force and torque on a two-dimensional circular cross-section of a non-viscous eccentric layered compressible cylinder in acoustical standing waves

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Chinese Physics B 2021年第2期30卷 355-366页

作者： f G Mitri Santa fe NM 87508USA

The purpose of this study is to develop an analytical formalism and derive series expansions for the time-averaged force and torque exerted on a compound coated compressible liquid-like cylinder,insonified by acoustic standing waves having an arbitrary angle of incidence in the polar(transverse)*** host medium of wave propagation and the eccentric liquid-like cylinder are *** computations illustrate the theoretical analysis with particular emphases on the eccentricity of the cylinder,the angle of incidence and the dimensionless size parameters of the inner and coating cylindrical fluid *** method to derive the acoustical scattering,and radiation force and torque components conjointly uses modal matching with the addition theorem,which adequately account for the multiple wave interaction effects between the layer and core fluid *** results demonstrate that longitudinal and lateral radiation force components ***,an axial radiation torque component is quantified and computed for the non-absorptive compound cylinder,arising from geometrical asymmetry considerations as the eccentricity *** computational results reveal the emergence of neutral,positive,and negative radiation force and torque depending on the size parameter of the cylinder,the eccentricity,and the angle of incidence of the insonifying ***,based on the law of energy conservation applied to scattering,numerical verification is accomplished by computing the extinction/scattering energy *** results may find some related applications in fluid dynamics,particle trapping,mixing and manipulation using acoustical standing waves.

关键词： radiation force radiation torque liquid compound cylinder multiple scattering acoustical standing waves

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