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Signal Transduction and Targeted Therapy 2023年第1期8卷 10-12页

作者： Rayhane nchioua Federica Diofano Sabrina Noettger Pascal von maltitz Steffen Stenger Fabian Zech jan münch Konstantin m.J.Sparrer Steffen Just Frank Kirchhoff Institute of molecular Virology Ulm University Medical CenterUlmGermany molecular Cardiology Department of Internal Medicine IIUlm UniversityUlmGermany Institute of medical microbiology and Hygiene Ulm University Medical CenterUlmGermany

Dear Editor,Since its first description in South Africa in November 2021,the SARS-CoV-2 Omicron variant rapidly outcompeted the previously dominating Delta *** is the fifth variant of concern(VOC).It contains an unusually high number of mutations compared to previous VOCs,especially in the viral Spike protein,and shows high transmissibility and efficient escape of neutralizing antibodies.

关键词： Strong neutral Omi

An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2694-2708页

作者： mirja Harms monica mWHabib Simona Nemska Antonella Nicolò Andrea Gilg Nico Preising Pandian Sokkar Sara Carmignani martina Raasholm Gilbert Weidinger Gönül Kizilsavas manfred Wagner Ludger Ständker Ashraf HAbadi Hassan Jumaa Frank Kirchhoff Nelly Frossard Elsa Sanchez-Garcia jan münch Institute of molecular Virology Ulm University Medical CenterUlm 89081Germany Department of Pharmaceutical Chemistry Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt Laboratoire D'Innovation Thérapeutique UMR7200 CNRS/Universitéde Strasbourg and LabEx MEDALISFacultéde PharmacieIllkirch 67412France Institute of Immunology Ulm University Medical CenterUlm 89081Germany Core Facility Functional Peptidomics Ulm University Medical CenterUlm 89081Germany Center of medical Biotechnology University of Duisburg-EssenDuisburg 47057Germany max-Planck-Institute for Coal Research Düsseldorf 45470Germany Faculty of Allied Health Sciences Chettinad Hospital and Research InstituteChettinad Academy of Research and EducationKelambakkam 603103India max-Planck-Institut für molekulare Physiologie Dortmund 44227Germany Institute of Biochemistry and molecular Biology Ulm UniversityUlm 89081Germany max Planck Institute for Polymer Research Mainz 55128Germany

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases.A natural fragment of serum albumin,named EPI-X4,has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated *** generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/*** rational drug design allowed to increase the anti-CXCR4 activity of *** EPI-X4 derivative Jm#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist ***-X4 Jm#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse ***,topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic ***,rationally designed EPIX4 Jm#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic *** clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis,asthma and other CXCR4-associated diseases is highly warranted.

关键词： CXCR4 antagonist Asthma Allergy Inflammation Atopic dermatitis

Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2576-2585页

作者： Shuai Xia Qiaoshuai Lan Yun Zhu Chao Wang Wei Xu Yutang Li Lijue Wang Fanke Jiao Jie Zhou Chen Hua Qian Wang Xia Cai Yang Wu Jie Gao Huan Liu Ge Sun jan munch Frank Kirchhoff Zhenghong Yuan Youhua Xie Fei Sun Shibo Jiang Lu Lu Key Laboratory of medical molecular Virology(mOE/NHC/CAmS) School of Basic Medical Sciences and Biosafety Level 3 LaboratoryShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghaiChina National Key Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijingChina State Key Laboratory of Toxicology and medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina China Institute for Radiation Protection TaiyuanShanxiChina lnstitute of molecular Virology Ulm University Medical CenterUlmGermany Bioland Laboratory(Guangzhou Regenerative medicine and Health Guangdong Laboratory) GuangzhouGuangdongChina

The COVID-19 pandemic poses a global threat to public health and *** continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and *** this study,we identified that EK1 and cholesterol-coupled derivative of EK1,EK1C4,as pan-CoV fusion inhibitors,exhibit potent antiviral activity against SARS-CoV-2 infection in both lung-and intestine-derived cell lines(Calu-3 and Caco2,respectively).They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7(Alpha)and B.l.1.248(Gamma)as well as those with mutations in S protein,including N417T,E484K,N501Y,and D614G,which are common in South African and Brazilian *** structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral *** administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal ***1 showed good safety profiles in various animal models,supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.

关键词： clinical lung intestine

Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-jan Serneels Julie D.De Schutter Lies De Groef Lieve moons Steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

Uplifting the complexity of analysis for probabilistic security of electricity supply assessments using artificial neural networks

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Energy and AI

Energy and AI 2024年第3期17卷 313-326页

作者： Justin münch jan Priesmann marius Reich marius Tillmanns Aaron Praktiknjo mario Adam University of Applied Sciences Duesseldorf Centre of Innovative Energy SystemsMuensterstr.15640476 DuesseldorfGermany RWTH Aachen University E.ON Energy Research CenterChair for Energy System Economics(FCN-ESE)Mathieustrasse 1052074 AachenGermany

The energy sector faces rapid decarbonisation and decision-makers demand reliable assessments of the security of electricity supply. For this, detailed simulation models with a high temporal and technological resolution are required. When confronted with increasing weather-dependent renewable energy generation, probabilistic simulation models have proven. The significant computational costs of calculating a scenario, however, limit the complexity of further analysis. Advances in code optimization as well as the use of computing clusters still lead to runtimes of up to eight hours per scenario. However ongoing research highlights that tailor-made approximations are potentially the key factor in further reducing computing time. Consequently, current research aims to provide a method for the rapid prediction of widely varying scenarios. In this work artificial neural networks (ANN) are trained and compared to approximate the system behavior of the probabilistic simulation model. To do so, information needs to be sampled from the probabilistic simulation in an efficient way. Because only a limited space in the whole design space of the 16 independent variables is of interest, a classification is developed. Finally it required only around 35 min to create the regression models, including sampling the design space, simulating the training data and training the ANNs. The resulting ANNs are able to predict all scenarios within the validity range of the regression model with a coefficient of determination of over 0.9998 for independent test data (1.051.200 data points). They need only a few milliseconds to predict one scenario, enabling in-depth analysis in a brief period of time.

关键词： Security of electricity supply Probabilistic simulation metamodeling Artificial neural networks Regression

A LIOUVILLE THEOREm FOR STATIONARY INCOmPRESSIBLE FLUIDS OF VON mISES TYPE

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Acta mathematica Scientia 2019年第1期39卷 1-10页

作者： martin FUCHS jan müLLER Fachbereich 6.1 mathematik Universit?t des Saarlandes

We consider entire solutions u of the equations describing the stationary flow of a generalized Newtonian fluid in 2 D concentrating on the question, if a Liouville-type result holds in the sense that the boundedness of u implies its constancy. A positive answer is true for p-fluids in the case p > 1(including the classical Navier-Stokes system for the choice p = 2), and recently we established this Liouville property for the Prandtl-Eyring fluid model,for which the dissipative potential has nearly linear growth. Here we finally discuss the case of perfectly plastic fluids whose flow is governed by a von mises-type stress-strain relation formally corresponding to the case p = 1. It turns out that, for dissipative potentials of linear growth, the condition of μ-ellipticity with exponent μ m.

关键词： generalized Newtonian fluids perfectly plastic fluids von mises flow Liouville theorem

BOUNDARY PROCEDURES FOR THE TImE-DEPENDENT BURGERS' EQUATION UNDER UNCERTAINTY

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Acta mathematica Scientia 2010年第2期30卷 539-550页

作者： Per Pettersson jan Nordstrm Gianluca Iaccarino mechanical Engineering and Institute for Computational mathematical Engineering Stanford University Division of Scientific Computing Department of Information TechnologyUppsala University School of mechanical Industrial and Aeronautical EngineeringUniversity of the Witvatersrand Department of Aeronautics and Systems Integration FOIThe Swedish Defense Research Agency

The Burgers＇ equation with uncertain initial and boundary conditions is approximated using a Polynomial Chaos Expansion （PCE） approach where the solution is represented as a series of stochastic, orthogonal polynomials. The resulting truncated PCE system is solved using a novel numerical discretization method based on spatial derivative operators satisfying the summation by parts property and weak boundary conditions to ensure stability. The resulting PCE solution yields an accurate quantitative description of the stochastic evolution of the system, provided that appropriate boundary conditions are available. The specification of the boundary data is shown to influence the solution; we will discuss the problematic implications of the lack of precisely characterized boundary data and possible ways of imposing stable and accurate boundary conditions.

关键词： stochastic Burgers' equation uncertainty quantification polynomial chaos

A new design approach for the established flow region of vertical,dilute-phase pneumatic conveyors

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Particuology 2022年第7期20卷 10-20页

作者： John m.Wheeldon jan Baeyens Shuo Li Yimin Deng European Powder and Process Technology Longfellow DriveKetteringUnited Kingdom KU Leuven Department of Chemical EngineeringProcess and Environmental Technology LabJ.De Nayerlaan 52860 Sint-Katelijne-WaverBelgium Beijing University of Chemical Technology Beijing Advanced Centre of Smart Matter Science and EngineeringBeijingChina

An analysis has been completed for a comprehensive set of vertical,dilute-phase pneumatic conveying pressure drop data from an investigation by *** data were collected in the established flow region for eight different materials conveyed in 0.05-,0.10-,0.20-m internal diameter,20-m tall steel *** velocities derived from the pressure drop data were used to develop an equation of motion that includes terms for pipe diameter,terminal velocity,coefficient of restitution,and particle *** best data fit was achieved using the actual gas density and the actual gas velocity adjusted for *** the terminal velocity for voidage,an approach recommended by many investigators,did not improve the fit for reasons identified by the present *** the equation of motion,particle velocities were predicted and used to calculate total pressure drops that are within±15%of the measured *** calculated values also produce the characteristic trough-shaped total pressure drop curves allowing the minimum pressure drop gas velocity to be determined without recourse to a separate correlation.A comparison with other studies using shorter risers indicates that data from these studies likely include acceleration effects.A separate study will investigate this observation further.

关键词： Dilute-phase Vertical Pneumatic conveying Design equations Pressure drops

The role of zonal flows in reactive fluid closures

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Plasma Science and Technology 2018年第7期20卷 41-49页

作者： jan weiland Chalmers University of Technology and EURATOm-VR Association SE-41296 GothenburgSweden

We will give an overview of results obtained by our reactive fluid model. It is characterised as a fluid model where all moments with sources in the experiment are kept. Furthermore, full account is taken for the highest moments appearing in unexpanded denominators also including full toroidicity. It has been demonstrated that the strength of zonal flows is dramatically larger in reactive fluid closures than in those which involve dissipation. This gives a direct connection between the fluid closure and the level of excitation of turbulence. This is because zonal flows are needed to absorb the inverse cascade in quasi 2D turbulence. This also explains the similarity in structure of the transport coefficients in our model with a reactive closure in the energy equation and models which have a reactive closure because of zero ion temperature such as the Hasegawa-Wakatani model. Our exact reactive closure unifies several well-known features of tokamak experiments such as the L-H transition, internal transport barriers and the nonlinear Dimits upshift of the critical gradient for onset of transport. It also gives transport of the same level as that in nonlinear gyrokinetic codes. Since these include the kinetic resonance this confirms the validity of the thermodynamic properties of our model. Furthermore, we can show that while a strongly nonlinear model is needed in kinetic theory a quasilinear model is sufficient in the fluid description. Thus our quasilinear fluid model will be adequate for treating all relevant problems in bulk transport. This is finally confirmed by the reproduction by the model of the experimental power scaling of the confinement time Te ~ P-2/3. This confirms the validity of our reactive fluid model. This also gives credibility to our ITER simulations including the H-mode barrier. A new result is here, that alpha heating strongly reduces the slope of the H-mode barrier. This should significantly reduce the effects of ELm＇s.

关键词： turbulent transport improved mixing length estimates zonal flows toroidicity

Investigating the use cases of a novel heat battery in Dutch residential buildings

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Building Simulation 2023年第9期16卷 1675-1689页

作者： Shuwei Wang Pieter-jan Hoes jan L.m.Hensen Olaf C.G.Adan Pim A.J.Donkers Department of the Built Environment Eindhoven University of TechnologyEindhovenP.O.Box 5135600 MB Eindhoventhe Netherlands Department of Applied Physics Eindhoven University of TechnologyEindhovenP.O.Box 5135600 MB Eindhoventhe Netherlands TNO materials Solutions P.O.Box 62355600 HE Eindhoventhe Netherlands Cellcius BV Horsten 15612 AXEindhoventhe Netherlands

Recent advances in thermochemical storage technology have introduced a novel closed-loop thermal energy storage(TES)system,known as the heat battery(HB),which is believed to have great potential for aiding the energy transition in the built environment because of its higher energy density and neglectable storage loss compared to conventional TES *** order to investigate the potential use cases of the HB and provide practical feedback for its further development,this research employs a simulation-based approach to analyze its influence on building performance in various use cases within Dutch residential *** including the homeowner,distribution system operator,and district heating system operator are identified,and a preliminary list of use cases is defined based on relevant literature and input from the HB *** simulation approach is conducted to predict key performance indicators for each *** Kruskal-Wallis test was employed to sort and scrutinize the simulation outcomes and discern the significance of each use case *** findings demonstrated that the HB holds the potential to diminish both the operational energy cost by up to 30%for the homeowners and the peak heating load transmitted from the building to the district heating system.

关键词： thermochemical storage building performance simulation use case solar energy demand-side management