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Extracellular vesicles in liver disease and beyond

World Journal of Gastroenterology 2018年第40期24卷 4519-4526页

作者： laura Morán Francisco Javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain

Extracellular vesicles(EVs) are membrane-derived vesicles which can be released by different cell types, including hepatocytes, hepatic stellate cells and immune cells in normal and pathological conditions. EVs carry lipids, proteins, coding and non-coding RNAs and mitochondrial DNA causing modifications on the recipient cells. These vesicles are considered potential biomarkers and therapeutic agents for human diagnostic and prognostic due to their function as intercellular mediators of cell-cell communication within the liver and between other organs. However, the development and optimization of methods for EVs isolation is required to characterize their biological functions as well as their potential as a treatment option in the clinic. Nevertheless, many questions remain unanswered related to the function of EVs under physiological and pathological conditions. In the current editorial, the results obtained in different studies that investigated the role of intrahepatic EVs during liver diseases, including drug-induced liver injury, non-alcoholic fatty liver, nonalcoholic steatohepatitis, alcoholic liver disease and hepatocellular carcinoma and extrahepatic EVs in remote organs during pathological events such as pulmonary disease, cardiovascular diseases, neurodegenerative disorders e.g., Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as in immunopathological processes, are discussed. Although much light needs to be shed on the mechanisms of EVs, these membranederived vesicles represent both a novel promising diagnostic, and a therapeutic tool for clinical use that we emphasize in the current editorial.

关键词： Extracellular vesicles microRNA Hepatocytes Drug-induced liver injury Alcoholic liver disease Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Hepatocellular carcinoma

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Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

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Horticulture Research 2016年第1期3卷 198-207页

作者： laura Dougherty Yuandi Zhu Kenong Xu Horticulture Section School of Integrative Plant ScienceCornell UniversityNew York State Agricultural Experiment StationGenevaNY 14456USA Department of Pomology China Agricultural UniversityBeijing 100193China

Phytohormone ethylene largely determines apple fruit shelf life and *** studies demonstrated that MdACS1 and MdACS3a,which encode 1-aminocyclopropane-1-carboxylic acid synthases(ACS),are crucial in apple fruit ethylene ***1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening,while MdACS3a has been regarded a main regulator for ethylene production transition from system 1(during fruit development)to system 2(during fruit ripening).However,MdACS3a was also shown to have limited roles in initiating the ripening process *** better assess their roles,fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled *** was accomplished using an existing marker(ACS1)for MdACS1 and two markers(CAPS866 and CAPS870)developed here to specifically detect the two null alleles(ACS3a-G289V and Mdacs3a)of *** total,952 Malus accessions were allelotyped with the three *** major findings included:The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable;allele MdACS1–2 was significantly associated with low ethylene and slow softening;under the same background of the MdACS1 allelotypes,null allele Mdacs3a(not ACS3a-G289V)could confer a significant delay of ethylene peak;alleles MdACS1–2 and Mdacs3a(excluding ACS3a-G289V)were highly enriched in *** and *** when compared with those in *** findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a.

关键词： effect softening finding

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WATER CONSERVATION: OBSERVATIONS FROM A HIGHER EDUCATION FACILITY MANAG EMENT P ERSP ECTIVE

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Journal of Green Building 2016年第3期11卷 162-182页

作者： Anthony Cupido laura Steinberg Brian Baetz Mohawk College HamiltonON.CanadaL8N 3T2 Department of Civil Engineering Syracuse UniversitySyracuseNY13244 Department of Civil Engineering McMaster UniversityHamiltonON.CanadaL8S 4L7.

Sustainable or green building practices have been adopted by most higher educa-tion institutions for their new campus buildings,major renovations and daily *** paper provides a synthesis of opinions and existing practices related to water conservation in institutional green buildings of member institutions of APPA(formerly the Association of Physical Plant Administrators).A specific focus regard-ing waterless urinals and their operation was attempted.A web-based survey and follow-up one-to-one interviews were utilized to extract information and data from these industry *** survey evaluated the institution’s use of policy related to sustainable building practices and focused on their approaches to water *** preferences are provided and barriers to some water conser-vation practices and approaches have been *** challenges are evident,particularly as they relate to waterless *** is clear that higher educa-tion institutions are engaging in water conservation practices across Canada and the United *** work contributes to a foundation for future research and analysis related to best-management practices for water conservation in the higher education sector.

关键词： water conservation higher education LEED® rainwater harvesting waterless urinals policy

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Parameter identification through mode isolation for reaction-diffusion systems on arbitrary geometries

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International Journal of Biomathematics 2018年第4期11卷 149-178页

作者： laura Murphy Chandrasekhar Venkataraman Anotida Madzvamuse School of Mathematical and Physical SciencesUniversity of Sussex Department of Mathematics Brighton BNI 9QH UK School of Mathematics and StatisticsUniversity of St Andrews St Andrews UK School of Mathematical and Physical SciencesUniversity of Sussex Department of Mathematics Brighton BN1 9QH UK

We present a computational framework for isolating spatial patterns arising in the steady states of reaction-diffusion systems. Such systems have been used to model many nat- ural phenomena in areas such as developmental and cancer biology, cell motility and material science. In many of these applications, often one is interested in identifying parameters which will lead to a particular pattern for a given reaction-diffusion model. To attempt to answer this, we compute eigenpairs of the Laplacian on a variety of domains and use linear stability analysis to determine parameter values for the system that will lead to spatially inhomogeneous steady states whose patterns correspond to particular eigenfunctions. This method has previously been used on domains and surfaces where the eigenvalues and eigenfunctions are found analytically in closed form. Our contribution to this methodology is that we numerically compute eigenpairs on arbitrary domains and surfaces. Here we present examples and demonstrate that mode isolation is straightforward especially for low eigenvalues. Additionally, we show that in some cases the inhomogeneous steady state can be a linear combination of eigenfunctions. Finally,we show an example suggesting that pattern formation is robust on similar surfaces in cases that the surface either has or does not have a boundary.

关键词： Reaction diffusion systems finite elements parameter identification eigen-value problem.

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Fekete-Gauss Spectral Elements for Incompressible Navier-Stokes Flows:The Two-Dimensional Case

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Communications in Computational Physics 2013年第5期13卷 1309-1329页

作者： laura Lazar Richard Pasquetti Francesca Rapetti Lab.J.A.Dieudonne UMR 7351 CNRS UNSUniversite de Nice-Sophia Antipolis06108 Nice Cedex 02France

Spectral element methods on simplicial meshes,say TSEM,show both the advantages of spectral and finite element methods,i.e.,spectral accuracy and geometrical *** present a TSEM solver of the two-dimensional(2D)incompressible Navier-Stokes equations,with possible extension to the 3D *** uses a projection method in time and piecewise polynomial basis functions of arbitrary degree in *** so-called Fekete-Gauss TSEM is employed,i.e.,Fekete(***)points of the triangle are used as interpolation(***)*** the sake of consistency,isoparametric elements are used to approximate curved *** resolution algorithm is based on an efficient Schur complement method,so that one only solves for the element boundary ***,the algebraic system is never assembled,therefore the number of degrees of freedom is not *** accuracy study is carried out and results are provided for classical benchmarks:the driven cavity flow,the flow between eccentric cylinders and the flow past a cylinder.

关键词： Spectral elements simplicial meshes Fekete-Gauss approximation Navier-Stokes equations projection methods domain decomposition

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SPACE AS PARADIGM OF INTERNET REGULATION

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Frontiers of Law in China-Selected Publications from Chinese Universities 2018年第3期13卷 412-427页

作者： laura Münkler Faculty of Law LMU Munich Munich 80539 Germany

Right now internet regulation is standing at the crossroads. Its problem-driven evolution has led to a conglomerate of seemingly diverse rules, which can hardly be structured as one cohesive area of law. Nevertheless, a consolidation of these rules as one cross-sectional field of law is can be identified. The discussion about the terms ＂internet regulation＂ and ＂internet governance＂ as well as recent developments in this field indicate that a paradigm shift in internet regulation is ongoing. Whereas self-regulation has been the determining mode of internet governance for a long time, internet regulation in the sense of public regulation is currently gaining more influence. This transformation is accompanied by the rising importance of a traditional paradigm of law： the idea of space. Even though the idea of space finds itself challenged with regard to the internet, it can give substance to many different aspects of internet regulation.

关键词： internet governance internet regulation space

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Second-Order Invariant Domain Preserving ALE Approximation of Euler Equations

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Communications on Applied Mathematics and Computation 2023年第2期5卷 923-945页

作者： Jean-Luc Guermond Bojan Popov laura Saavedra Department of Mathematics Texas A&M UniversityCollege StationUSA Departamento de Matemática Aplicada a la Ingeniería Aeroespacial Universidad Politécnica de MadridMadridSpain

An invariant domain preserving arbitrary Lagrangian-Eulerian method for solving non-linear hyperbolic systems is *** numerical scheme is explicit in time and the approximation in space is done with continuous finite *** method is made invar-iant domain preserving for the Euler equations using convex limiting and is tested on vari-ous benchmarks.

关键词： Conservation equations Hyperbolic systems Arbitrary Lagrangian-Eulerian Moving meshes Invariant domains High-order method Convex limiting Finite element method

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The Old and the New: Designs to Enhance Cesano Maderno Old Town through a Regenerative Structure

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Built Heritage 2017年第4期1卷 52-70页

作者： laura Anna Pezzetti Department of Architecture Built Environment and Construction EngineeringPolitecnico di MilanoMilanItaly

The relationship between the old and the new is a specific theme of architecture that bears witness not so much to the original appearance of the old but to its enduring meaning in historic Italian and European *** complex palimpsest of signs,memories,and overwriting that time has layered on built forms opens questions of meaning that can be untangled only in the relationship between history,site and *** investigation of structural characters of places and their relationships with cultural assets and heritage provides a layered set of readings,which is itself the forerun of an urban landscape design *** preserving the integrity of the material traces,there can only be the *** test bench is therefore the project as a cognitive act around which to build‘case by case’the strategies for recovering urban *** series of projects for Cesano Maderno old town,north of Milan,exemplifies a design-led approach to the built heritage and historic urban landscape in which reading tools,conservation and design are shown in their mutual *** this dialectic between the old and the new,the design is part of the architecture of time where the new,working through light reversible overwriting and measured grafting,becomes a further layer in the historical palimpsest and the authentic form of its enhancement and *** project strategies-from pure conservation to new architectural grafting,from reuse to overwriting-the sequence of designs give shape to a‘regenerative structure’that enhances as a system and for public use a set of introverted Baroque buildings and spaces along a historical promenade,re-centring the city around its brownfield core.

关键词： urban interpretative tools historic public spaces and building enhancement and reuse insertion overwriting grafting historic urban landscape

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***-an interactive climate analysis web platform

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International Journal of Digital Earth 2021年第3期14卷 338-356页

作者： laura Zepner Pierre Karrasch Felix Wiemann Lars Bernard Chair of Geoinformatics Technische Universität DresdenDresdenGermany AED-SICAD GmbH BonnGermany

This article describes the conception and implementation of a web platform which uses special charts and maps for climate monitoring and *** first it gives an overview of related web applications and their advantages and *** is followed by a basic introduction of current technologies and methods for working with climate data,geospatial web services and visualization ***,the implementation based on prior defined requirements is presented and its strengths and limitations are *** application provides several basic charts for climate analysis,as well as a more complex one which uses a standardized visualization concept which is suitable for comparing different local climates(Walter-LiethStandard).The charts are based on different interpolated datasets with global coverage as well as data from the Global Historical Climate Network(GHCN).Overall,the application enables users to generate individual historical climate charts from the beginning of the twentieth century until present day.

关键词： Climate monitoring WalterLieth charts Köppen-Geiger classification user interface design education information visualization

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The role of p53 in developmental syndromes

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Journal of Molecular Cell Biology 2019年第3期11卷 200-211页

作者： Margot E.Bowen laura D.Attardi Division of Radiation and Cancer Biology in the Department of Radiation Oncology Stanford University School of MedicineStanfordCA 94305USA Department of Genetics Stanford University School of MedicineStanfordCA 94305USA

While it is well appreciated that loss of the p53 tumor suppressor protein promotes cancer,growing evidence indicates that increased p53 activity underlies the developmental defects in a wide range of genetic *** inherited or de novo mutations that cause these syndromes affect diverse cellular processes,such as ribosome biogenesis,DNA repair,and centriole duplication,and analysis of human patient samples and mouse models demonstrates that disrupting these cellular processes can activate the p53 ***,many of the developmental defects in mouse models of these syndromes can be rescued by loss of p53,indicating that inappropriate p53 activation directly contributes to their pathogenesis.A role for p53 in driving developmental defects is further supported by the observation that mouse strains with broad p53 hyperactivation,due to mutations affecting p53 pathway components,display a host of tissue-specific developmental defects,including hematopoietic,neuronal,craniofacial,cardiovascular,and pigmentation ***,germline activating mutations in TP53 were recently identified in two human patients exhibiting bone marrow failure and other developmental *** in mice suggest that p53 drives developmental defects by inducing apoptosis,restraining proliferation,or modulating other developmental programs in a cell type-dependent ***,we review the growing body of evidence from mouse models that implicates p53 as a driver of tissue-specific developmental defects in diverse genetic syndromes.

关键词： p53 Mdm2 development embryo congenital defect syndrome genetic disorder

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