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Therapeutic potential of mesenchymal stem cells in the treatment of acute liver failure

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World Journal of Gastroenterology 2022年第28期28卷 3627-3636页

作者： CARL RANDALL HARRELL Dragica Pavlovic Valentin Djonov Vladislav Volarevic Regenerative Processing Plant LLC Palm HarborFL 34176United States Department of Genetics Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Institute of Anatomy University of BernBern 3012Switzerland Department of Medical Genetics and Microbiology and Immunology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

Acute liver failure(ALF)is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease.Mesenchymal stem cells(MSCs)are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF.MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages,reduce production of inflammatory cytokines in T lymphocytes,suppress hepatotoxicity of natural killer T(NKT)cells and promote generation and expansion of immunosuppressive T,B and NKT regulatory cells in acutely inflamed liver.Due to their nano-sized dimension and lipid envelope,intravenously injected MSC-derived exosomes(MSC-Exos)may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes.Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver,suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF.In this review,we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.

关键词： Mesenchymal stem cells Acute liver failure Therapy Immunomodulation Regeneration

The role of mesenchymal stem cell-derived exosomes in tumor progression

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BIOCELL 2023年第8期47卷 1757-1769页

作者： carl randall HARREL VALENTIN DJONOV ANA VOLAREVIC DRAGICA PAVLOVIC VLADISLAV VOLAREVIC Regenerative Processing Plant LLCFloridaUSA Institute of Anatomy University of BernBernSwitzerland Department of Psychology Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia Department of Genetics Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia Department of Microbiology and Immunology Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia

Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.

关键词： Mesenchymal stem cells Exosomes Immune response Therapy Malignant diseases

Scaling granular material with polygonal particles in discrete element modeling

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Particuology 2023年第4期75卷 151-164页

作者： Alireza Ahmadi Stefan Larsson carl Wersall KTH Royal Institute of Technology Division of Soil and Rock MechanicsBrinellvagen 2310044StockholmSweden

Despite advancements in computational resources,the discrete element method(DEM)still requires considerable computational time to solve detailed problems,especially when it comes to the large-scale models.In addition to the geometry scale of the problem,the particle shape has a dramatic effect on the computational cost of DEM.Therefore,many studies have been performed with simplified spherical particles or clumps.Particle scaling is an approach to increase the particle size to reduce the number of particles in the DEM.Although several particle scaling methods have been introduced,there are still some disagreements regarding their applicability to certain aspects of problems.In this study,the effect of particle scalping on the shear behavior of granular material is explored.Real granular particles were scanned and imported as polygonal particles in the direct shear test.The effect of particle size distri-bution,particle angularity,and the amount of scalping were investigated.The results show that particle scalping can simulate the correct shear behavior of the model with significant improvement in computational time.Also,the accuracy of the scalping method depends on the particle angularity and particle size range.

关键词： Particle scaling Direct shear test Discrete element method PFC Polygonal shape Granular material

A Tropical View on Landau-Ginzburg Models

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Acta Mathematica Sinica,English Series 2024年第1期40卷 329-382页

作者： Michael carl Max PUMPERLA Bernd SIEBERT Alfred-Delp-Str.2 73430 AalenGermany IU Internationale Hochschule Juri-Gagarin-Ring 15299084 ErfurtGermany AnyscaleInc.2080 Addison St Ste 7BerkeleyCA 94704USA Department of Mathematics The Univ.of Texas at Austin2515 SpeedwayAustinTX 78712USA

This paper,largely written in 2009/2010,fits Landau-Ginzburg models into the mirror symmetry program pursued by the last author jointly with Mark Gross since 2001.This point of view transparently brings in tropical disks of Maslov index 2 via the notion of broken lines,previously introduced in two dimensions by Mark Gross in his study of mirror symmetry for P2.A ma jor insight is the equivalence of properness of the Landau-Ginzburg potential with smoothness of the anticanonical divisor on the mirror side.We obtain proper superpotentials which agree on an open part with those classically known for toric varieties.Examples include mirror LG models for non-singular and singular del Pezzo surfaces,Hirzebruch surfaces and some Fano threefolds.

关键词： Landau-Ginzburg model mirror symmetry tropical disk broken line wall structure scattering diagram Gross-Siebert program del Pezzo surface toric degeneration

Comparison of Adult Defendants' Forensic Psychiatric Evaluation in Criminal Courts between China' Mainland and Taiwan region:From Law to Clinical Practice

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Journal of Forensic Science and Medicine 2022年第1期8卷 32-40页

作者： Wai-Cheong carl Tam Department of Psychology Chung Yuan Christian UniversityTaoyuan CityTaiwanChina

The defendant’s mental capacity is often crucial in criminal procedure,and an expert witness may be requested to conduct a forensic psychiatric evaluation.This paper analyzes the law and clinical practice of adult defendants’forensic psychiatric evaluation in criminal courts between China' Mainland and Taiwan region.Results indicated that the law in Taiwan region explicitly mentioned more mental illness and mental capacity than the law in China' Mainland regarding forensic psychiatric evaluation.Concerning expert witnesses,China' Mainland has established a registration and management system,but in Taiwan region,the judge decides the expert witness’s admissibility.Furthermore,clinical evaluation guidelines have been promulgated in China' Mainland,while none in Taiwan region.Implications of the findings were discussed.

关键词： Criminal responsibility expert witness forensic assessment legal competence

Tree sapling vitality and recovery following the unprecedented 2018 drought in central Europe

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森林生态系统:英文版 2023年第5期10卷 597-606页

作者： Mirela Beloiu Schwenke Valeska Schönlau carl Beierkuhnlein Institute of Terrestrial Ecosystems ETH ZurichZurichSwitzerland Department of Biogeography University of BayreuthUniversitätsstraße 3095447BayreuthGermany GIB Geographical Institute Bayreuth University of Bayreuth95447BayreuthGermany BayCEER Bayreuth Center of Ecology and Environmental Research University of Bayreuth95448BayreuthGermany

Background:Ongoing climate change is anticipated to increase the frequency and intensity of drought events,thereby affecting forest recovery dynamics and elevating tree mortality.The drought of 2018,with its exceptional intensity and duration,had a significant adverse impact on tree species throughout Central Europe.However,our understanding of the resistance to and recovery of young trees from drought stress remains limited.Here,we examined the recovery patterns of native deciduous tree sapling species following the 2018 drought,and explored the impact of soil depth,understory vegetation,and litter cover on this recovery.Methods:A total of 1,149 saplings of seven deciduous tree species were monitored in the understory of old-growth forests in Northern Bavaria,Central Germany.The vitality of the saplings was recorded from 2018 to 2021 on 170 plots.Results:Fagus sylvatica was the most drought-resistant species,followed by Betula pendula,Acer pseudoplatanus,Quercus spp.,Corylus avellana,Carpinus betulus,and Sorbus aucuparia.Although the drought conditions persisted one year later,all species recovered significantly from the 2018 drought,albeit with a slight decrease in vitality by 2021.In 2018,the drought exhibited a more pronounced adverse effect on saplings in deciduous forests compared to mixed and coniferous forests.Conversely,sapling recovery in coniferous and mixed forests exceeded that observed in deciduous forests in 2019.The pivotal factors influencing sapling resilience to drought were forest types,soil depth,and understory vegetation,whereas litter and forest canopy cover had a negative impact.Conclusion:Long-term responses of tree species to drought can be best discerned through continuous health monitoring.These findings demonstrate the natural regeneration potential of deciduous species in the context of climate change.Selective tree species planting,soil management practices,and promoting understory diversity should be considered when implementing adaptive management strategies to enhance forest resi

关键词： Drought stress Temperate forest Deciduous trees Climate change Extreme events Soil depth

Situation analytics—at the dawn of a new software engineering paradigm

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Science China(Information Sciences) 2018年第5期61卷 5-18页

作者： carl K.CHANG Department of Computer Science Iowa State University

In this paper, I first review the seminal work by Thomas Kuhn — The Structure of Scientific Revolutions — and elaborate my view on paradigm shifts in software engineering research and practice as it turns 50 years old in 2018. I then examine major undertakings of the computing profession since early days of modern computing, especially those done by the software engineering community as a whole. I also enumerate anomalies and crises that occurred at various stages, and the attempts to provide solutions by the software engineering professionals in the past five decades. After providing such a background, I direct readers’ attention toward emerging anomalies in software engineering, at a severity level that is causing another software engineering crisis, and suggest a set of criteria for feasible solutions. The main theme of this paper is to advocate that situation analytics, equipped with necessary definitions of essential concepts including situation and intention as parts of a new computational framework, can serve as the foundation for a new software engineering paradigm named the Situation-Centric Paradigm. In this framework, situation is considered a new abstraction for computing and is clearly differentiated from the widely accepted existing abstractions, namely function and object. I argue that the software engineering professionals will inevitably move into this new paradigm, willingly or unwillingly, to empower Human-Embedded Computing(HEC) and End-User Embedded Computing(EUEC), much more than what they have done with traditional humancentered or user-centric computing altogether. In the end, I speculate that an ultimate agile method may be on the rise, and challenge readers to contemplate "what if" hundreds of thousands "end-user developers"emerge into the scene where the boundaries between end users and developers become much more blurred.

关键词： ultimate agile method context intention Internet of things paradigm situation software engineering human-embedded computing

Campylobacterjejuni in Musca domestica： An examination of survival and transmission potential in light of the innate immune responses of the house flies

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Insect Science 2017年第4期24卷 584-598页

作者： Carson Gill Simon Bahrndorff carl Lowenberger Department of Biological Sciences Simon Fraser University 8888 University Drive Burnaby BC Canada National Food Institute Technical University of Denmark 2800 Kongens Lyngby Denmark

The house fly, Musca domestica, has been implicated as a vector of Campy- lobacter spp., a major cause of human disease. Little is known whether house flies serve as biological amplifying hosts or mechanical vectors for Campylobacterjejuni. We in- vestigated the period after C. jejuni had been ingested by house flies in which viable C. jejuni colonies could be isolated from whole bodies, the vomitus and the excreta of adult M. domestica and evaluated the activation of innate immune responses of house flies to ingested C. jejuni over time. C. jejuni could be cultured from infected houseflies soon after ingestion but no countable C. jejuni colonies were observed 〉 24 h postingestion. We detected viable C. jejuni in house fly vomitus and excreta up to 4 h after ingestion, but no viable bacteria were detected 〉 8 h. Suppression subtractive hybridization identi- fied pathogen-induced gene expression in the intestinal tracts of adult house flies 4-24 h after ingesting C. jejuni. We measured the expression of immune regulatory （thor, JNK, and spheroide） and effector （cecropin, diptericin, attacin, defensing, and lysozyme） genes in C. jejuni-infected and -uninfected house flies using quantitative real time PCR. Some house fly factor, or combination of factors, eliminates C. jejuni within 24 h postingestion. Because C. jejuni is not amplified within the body of the housefly, this insect likely serves as a mechanical vector rather than as a true biological, amplifying vector for C. jejuni, and adds to our understanding of insect pathogen interactions.

关键词： antimicrobial peptides Campylobacter spp. Campylobacteriosis house fly innate immunity Musca domestica suppression subtractive hybridization （SSH） vector

Extending the production boundary of the System of National Accounts (SNA) to classify and account for ecosystem services

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Ecosystem Health and Sustainability 2018年第11期4卷 19-32页

作者： Mark Eigenraam carl Obst Institute for the Development of Environmental-Economic Accounting(IDEEA) MelbourneAustralia

There is a broad acceptance to depicting the relationship between ecosystems and human well-being using the concept of ecosystem services,emanating in large from the findings and research published in the Millennium Ecosystem Assessment in 2005.While the generic concept of ecosystem services provides an excellent platform for discussion,the ongoing lack of clarity surrounding the definition,clas sification and measurement of ecosystem services,is emerging as a barrier to more extensive collaboration across disciplines.This paper applies the principles of national accounting to bring additional rigor and consistency to the discussion on ecosystem services.In this paper we revisit four fundamental aspects of the System of National Accounts(SNA)that underpin the measurement of the economy,namely,the definition of economic units;the definition of production;the recording of transactions and the recording assets.By considering each of these aspects in the context of the United Nations'System of Environmental-Economic Accounting,the paper presents a framework to describe the relationship between ecosystems and human aativity that can then be used to consistently define,classify,measure and account for ecosystem services.

关键词： Ecosystem accounting system of national accounts ecosystem services ecosystem asset environmental accounting