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Correlative optical photothermal infrared and X-ray fluorescence for chemical imaging of trace elements and relevant molecular structures directly in neurons

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Light(Science & Applications) 2021年第8期10卷 1536-1545页

作者： Nadja Gustavsson Agnes Paulus Isak Martinsson Anders Engdahl Kadda Medjoubi Konstantin Klementiev Andrea Somogyi tomas deierborg Ferenc Borondics Gunnar K Gouras Oxana Klementieva Medical Microspearoscopy Department of Experimental Medical ScienceLund University22180 LundSweden. Experimental Neuroinflammation Lab Department of Experimental Medical ScienceLund University22180 LundSweden. Experimental Dementia Research Department of Experimental Medical ScienceLund University22180 LundSweden. Synchrotron SOLEIL L'Orme des Merisiers91192 Gif Sur Yvette CedexFrance. MAX IV Laboratory 22100 LundSweden. Lund Institute for advanced Neutron and X-ray Science(LINXS) 22370 LundSweden

Alzheimer's disease(AD)is the most common cause of dementia,costing about 1%of the global *** of clinical trials targeting amyloid-βprotein(Aβ),a key trigger of AD,have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity,which are very difficult to address by available ***,we combine two imaging modalities that stand at opposite ends of the electromagnetic spectrum,and therefore,can be used as complementary tools to assess structural and chemical information directly in a single *** label-free super-resolution microspectroscopy for sub-cellular imaging based on novel optical photothermal infrared(O-PTIR)and synchrotron-based X-ray fluorescence(S-XRF)nano-imaging techniques,we capture elemental distribution and fibrillary forms of amyloid-βproteins in the same neurons at an unprecedented *** results reveal that in primary AD-like neurons,iron clusters co-localize with elevated amyloidβ-sheet structures and oxidized ***,our O-PTIR/S-XRF results motivate using high-resolution multimodal microspectroscopic approaches to understand the role of molecular structures and trace elements within a single neuronal cell.

关键词： elevated elements complementary

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Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

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Translational Neurodegeneration 2023年第1期12卷 801-823页

作者： Luis Enrique Arroyo-García Sara Bachiller Rocío Ruiz Antonio Boza-Serrano Antonio Rodríguez-Moreno tomas deierborg Yuniesky Andrade-Talavera AndréFisahn Neuronal Oscillations Laboratory Division of NeurogeriatricsCenter for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164 SolnaSweden Experimental Neuroinflammation Laboratory Department of Experimental Medical ScienceLund UniversityBMC B1122184 LundSweden Clinical Unit of Infectious Diseases Microbiology and ParasitologyInstitute of Biomedicine of Seville(IBiS)Virgen del Rocío University HospitalCSICUniversity of SevilleSevilleSpain Department of Biochemistry and Molecular Biology University of SevilleCalle Profesor García González Nº241012 SevilleSpain Laboratory of Cellular Neuroscience and Plasticity Department of PhysiologyAnatomy and Cellular BiologyUniversidad Pablo de OlavideCarretera de Utrera Km-141013 SevilleSpain Department of Biosciences and Nutrition NeoKarolinska Institutet14183 HuddingeSweden

Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment *** is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in ***,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains *** Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of *** addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(KO).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal *** found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma ***-more,the 5×FAD mice lacking gal3(5×FAD-Gal3KO)exhibited WT-like gamma network dynamics and decreased Aβplaque *** We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance ***,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

关键词： Galectin-3 Gamma oscillations Neuronal network dynamics Fast-spiking interneurons Alzheimer’s disease models Neuroinflammation TD139 Hippocampus

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Insights from a proteomic atlas of human Alzheimer's disease brain tissue

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Neural Regeneration Research 2025年第3期20卷 799-800页

作者： tomas Kavanagh Eleanor Drummond Brain and Mind Centre and School of Medical Sciences University of SydneyCamperdownNSWAustralia

There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the disease mechanisms driving AD is an essential factor that will facilitate the identification of new, effective drug targets.

关键词： Alzheimer clinical driving

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New regulators of systemic iron homeostasis

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2270-2271页

作者： tomas Ganz Center for Iron Disorders Department of MedicineDavid Geffen School of MedicineUCLALos AngelesCAUSA

In a recent study published in Blood,Jiang et al.1 describe two new mechanisms that may contribute to systemic iron *** first identify the methylcytosine dioxygenase Tetl as an iron-dependent epigenetic regulator of multiple downstream target *** through the target genes,they go on to show that one of them,Rnf217,is a long-sought E3 ubiquitin ligase that regulates the degradation of the unique cellular iron exporter ferroportin in response to its ligand,the master iron-regulatory hormone hepcidin.

关键词： Blood homeostasis sought

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DISCONTINUOUS GALERKIN CALCULATIONS FOR A NONLINEAR PDE MODEL OF DNA TRANSCRIPTION WITH SHORT, TRANSIENT AND FREQUENT PAUSING

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Journal of Computational Mathematics 2014年第6期32卷 601-629页

作者： Lisa Davis tomas Gedeon Department of Mathematical Sciences Montana State University P.O. Box 172400 Bozeman MT 59717

A discontinuous Galerkin finite element method is used to approximate solutions to a classical traffic flow PDE. This PDE is used to model the biological process of transcription; the process of transferring genetic information from DNA either to mRNA or to rRNA. The transcription process is punctuated by short, frequent RNAP pauses which are incorporated into the model as traffic lights. These pauses cause a delay in the average transcription process. The DG solution of the nonlinear model is used to calculate the delay and to determine the effect of the pauses on the average transcription time. Numerical error measurements between the DG solution and the true solution （derived by the method of characteristics） are given for a simple model problem. It shows an excellent agreement in a neighborhood away from the shocks as well as C9（Ax） convergence for the delay calculation. Preliminary parameter studies indicate that in a system with multiple pauses both the location and time duration of the pauses can significantly affect the average delay experienced by an RNAP.

关键词： Discontinuous Galerkin finite element method Transcription LWR traffic flowmodel.

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Fast Modification of Microdischarge Emission Bands by Fracture of Sugar

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Chinese Physics Letters 2011年第8期28卷 304-306页

作者： Sergej Aman Juergen tomas AStreletskii Otto-von-Guericke University MagdeburgP.O.Box 412039106 MagdeburgGermany Institute of Chemical Physics RASKosygina 4Moscow 119991Russia

Intensive light pulses with widths of about 10 ns were observed during the crack propagation by cleavage of crystalline sugar at atmospheric *** observed light pulses were caused by a sequence of gas microdischarges(MDs).The pulses were detected in the UV/VIS and NIR wavelength *** the light pulses appear in the UV/VIS wavelength range,and then after a delay of about 0.4–1.2 ns in the NIR wavelength *** characteristic feature of MDs can be used for the characterization of crack propagation.

关键词： delay sugar Fast

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Neutral stochastic delay partial functional integro-differential equations driven by a fractional Brownian motion

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Frontiers of Mathematics in China 2013年第4期8卷 745-760页

作者： tomas CARABALLO Mamadou Abdoul DIOP Dpto. Ecuaciones Diferenciales y Analisis Numerico Universidad de Sevilla Apdo. de Correos 1160 41080-Sevilla Spain Universite Gaston Berger de Saint-Louis UFR SAT Departement de Mathematiques 234 Saint-Louis Senegal

This paper deals with the existence and uniqueness of mild solutions to neutral stochastic delay functional integro-differential equations perturbed by a fractional Brownian motion BH, with Hurst parameter H E （1/2, 1）. We use the theory of resolvent operators developed by R. Grimmer to show the existence of mild solutions. An example is provided to illustrate the results of this work.

关键词： Resolvent operator C0-semigroup Wiener process mild solution fractional Brownian motion

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My Journey to DNA Repair

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Genomics, Proteomics & Bioinformatics 2013年第1期11卷 2-7页

作者： tomas Lindahl Cancer Research UK London Research Institute Clare Hall Laboratories

I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have dis- covered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases I, III and IV. I discovered the mam- malian exonucleases DNase III （TREX1） and IV （FEN1）. Interestingly, expression of TREXI was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O6-methylguanine （O6mG） is repaired without removing the guanine from DNA, identifying a sur- prising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation.

关键词： DNA repair Base excision repair DNA glycosylase DNA exonuclease AlkB dioxygenase

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Simulation and calibration of granules using the discrete element method

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Particuology 2014年第1期12卷 40-43页

作者： Peter Müller Jürgen tomas Institute of Process Engineering Mechanical Process EngineeringOtto-von-Guericke University MagdeburgUniversitätsplatz 239106 MagdeburgGermany

The discrete element method （DEM）, developed by Cundall and 5track to solve geomecnamcai problems, is used to simulate the mechanical behavior of granules. According to the DEM, an individ ual granule can be modeled as a realistic mechanical system consisting of primary particles bonded by interaction forces. Cranulometric properties of the model material, zeolite 4A, have been measured to determine their macro properties. To investigate the compression behavior, a compression test was performed using a strength tester on single granules between two pistons. A modeled granule consisting of more than 22,000 primary particles was generated. The micro properties of the modeled granule have been precisely set to allow its macro properties to be equivalent to the macro properties of zeolite 4A granules. To calibrate the mechanical properties, diametrical compression was simulated using two rigid walls stressed at a constant stressing velocity, The force-displacement curve of the modeled granule at compression has been calibrated by the experimental curve of zeolite 4A.

关键词： Discrete element method Material behavior Granulation

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Analysis of the Water Film Behavior and its Breakup on Profile using Experimental and Numerical Methods

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Journal of Thermal Science 2014年第4期23卷 325-331页

作者： tomas MUZIK Pavel SAFARIK Antonín TUCEK TechSoft Engineering Na Pankraci 2614000 PragueCzech Republic CTU in Prague Department of Fluid Dynamics and ThermodynamicsTechnicka 416607 PragueCzech Republic

This paper deals with the description of water film behaviour on the airfoil NACA0012 using experimental and numerical methods. Properties of the water film on the profile and its breakup into droplets behind the profile are investigated in the aerodynamic tunnel and using CFD methods. The characteristic parameters of the water film, like its thickness and shape for different flow modes are described. Hereafter are described droplets drifted by the air, which water film is broken behind the profile.

关键词： NACA0012 profile water film droplets breakup CFD

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