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Mesenchymal stem cell-and extracellular vesicle-based therapies for Alzheimer's disease:progress,advantages,and challenges

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Neural Regeneration Research 2023年第8期18卷 1645-1651页

作者： Renata Guedes de Jesus Gonçalves Juliana Ferreira Vasques Almir Jordão da Silva-Junior Fernanda Gubert Rosalia Mendez-Otero Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto nacional de Ciência e tecnologia em Medicina Regenerativa Rio de JaneiroBrazil Plataformas Inovadoras em Terapias Avançadas Departamento de Ciência e Tecnologia-Ministério da Saúde(DECIT-MS)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Brazil Programa Redes de Pesquisa em Saúde no estado do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa Redes de Pesquisa em Nanotecnologia no estado do Rio de Janeiro Rio de JaneiroBrazil

Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.

关键词： Alzheimer's disease amyloid-β cell therapy cell transplantation exosomes extracellular vesicles mesenchymal stem cell micro vesicles neuroinflammation tau protein

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Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari Joséeduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil conselho nacional de desenvolvimento científico e tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(deN)in drinking water and Veh gavage],and RIF[HFCD,deN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and ezh2 were lower in HCC and RIF-groups(Per in HCC compared to RIF(Pepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(Pexpression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(Per in HCC compared to RIF,and the inverse was observed for miR-224(Pere was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin

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Brain scarring in infants:immunological insights from a neonatal hypoxic-ischemic encephalopathy model

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Neural Regeneration Research 2025年第10期20卷 2909-2910页

作者： Pedro Moreno Pimentel-Coelho Carlos Chagas Filho Biophysics Institute Federal University of Rio de JaneiroRio de JaneiroBrazil

Neonatal hypoxic-ischemic encephalopathy(HIe)is a significant cause of disability in *** brain function and accelerating neurological recovery may require a combination of neuroprotective and pro-regenerative treatments at different stages of *** the first hours after the neonatal insult are the most critical period for neuroprotection,the existence of secondary and tertiary mechanisms of brain injury offers the possibility of preventing delayed neurodegeneration in the subsequent days,weeks,or months(Levison et al.,2022).

关键词： neonatal protective hypoxic

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Renewable Polymers in Biomedical Applications:From the Bench to the Market

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Journal of Renewable Materials 2024年第4期12卷 643-666页

作者： Rauany Cristina Lopes Tamires Nossa Wilton Rogério Lustri Gabriel Lombardo Maria Inés errea eliane Trovatti department of Health and Biological Sciences University of Araraquara—UNIARAAraraquara14801-340Brazil Laboratory of Materials(LabMat)and Laboratory of Biopolymers(LaBioPol) Federal Institute of EducationScience and Technology of São Paulo Campus Itapetininga(IFSP)Itapetininga18.202‑000Brazil Instituto tecnológico de Buenos Aires Cidade Autônoma de Buenos AiresC1437FBCArgentina conselho nacional de Pesquisas científicas e Técnicas(CONICeT) Cidade Autônoma de Buenos AiresC1425FQBArgentina tecnologia YPF(Y-TeC) BerissoBuenos Aires1923Argentina

Polymers from renewable resources have been used for a long time in biomedical applications and found an irreplaceable role in some of *** uses have been increasing because of their attractive properties,contributing to the improvement of life quality,mainly in drug release systems and in regenerative *** using natural polymer,nano and microscale particles preparation,composites,blends and chemical modification strategies have been used to improve their properties for clinical *** many studies have been carried out with these natural polymers,the way to reach the market is long and only very few of them become commercially *** cellulose,bacterial cellulose,chitosan,poly(lactic acid)and starch can be found among the most studied polymers for biological applications,some with several derivatives already established in the market,and others with potential for *** this scenario this work aims to describe the properties and potential of these renewable polymers for biomedical applications,the routes from the bench to the market,and the perspectives for future developments.

关键词： Polymers renewable biomedical applications market

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Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： elisa Carolina Lange Pabulo Henrique Rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas Carolina Uribe-Cruz Mario Reis Alvares-da-Silva experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil conselho nacional de desenvolvimento científico e tecnológico(CNPq)researcher Brasília 71605-001Brazil

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic *** suggest ornithine aspartate(LOLA)as drug *** To analyze the influence of LOLA intake on gut microbiota using a nutritional model of *** Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were *** fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™*** Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides *** functional prediction provided two different metabolic profiles between MASLD and *** 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides *** 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA *** Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

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Changes in cellular proliferation and plasma products are associated with liver failure

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World Journal of Hepatology 2016年第32期8卷 1370-1383页

作者： Juliana Gil Melgaco Frederico Marianetti Soriani Pedro Henrique Ferreira Sucupira Leonardo Assaf Pinheiro Yasmine Rangel Vieira Jaqueline Mendes de Oliveira Lia Laura Lewis-Ximenez Cristina Carvalho Vianna Araújo Lúcio Filgueiras Pacheco-Moreira Gustavo Batista Menezes Oswaldo Goncalves Cruz Claudia Lamarca Vitral Marcelo Alves Pinto departamento de Microbiologia e Parasitologia Universidade Federal Fluminense Instituto Oswaldo Cruz/Fiocruz Laboratório de Desenvolvimento Tecnológico em Virologia departamento de Biologia Geral Instituto de Ciencias BiologicasUniversidade Federal de Minas Gerais Instituto Oswaldo Cruz/Fiocruz Ambulatório de Hepatites Virais Hospital Federal de Bonsucesso Laboratório de Imunofarmacologia Departamento de Bioquímica e ImunologiaInstituto de Ciencias BiológicasUniversidade Federal de Minas Gerais Fundacao Oswaldo Cruz Programa de Computacao Científica

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute *** Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were *** The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P ere the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunologi

关键词： Acute liver failure Cytokines Mitochondrial DNA Cellular immune response Hepatitis A virus

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Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model

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World Journal of Hepatology 2024年第12期16卷 1468-1479页

作者： Felipe Schütz Larisse Longo Melina Belén Keingeski eduardo Filippi-Chiela Carolina Uribe-Cruz Mário Reis Álvares-da-Silva Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Rio Grande do SulBrazil experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadas 3300MisionesArgentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil conselho nacional de desenvolvimento científico e tecnológico Brasilia 71.605-001Distrito FederalBrazil

BACKGROUND Genetic and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease(MASLD)*** To evaluate micro(mi)RNAs and lipophagy markers in an experimental model of metabolic dysfunction-associated steatohepatitis(MASH).MeTHODS Adult male Sprague Dawley rats were randomized into two groups:Control group(n=10)fed a standard diet;and intervention group(n=10)fed a high-fat-choline-deficient diet for 16 *** evaluation of li-pophagy markers in liver tissue[sirtuin-1,p62/sequestosome-1,transcription factor-eB,perilipin-2(Plin2),Plin3,Plin5,lysosome-associated membrane proteins-2,rubicon,and Cd36],and serum miRNAs were *** Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1(P=0.020)and p62/sequestosome-1(Pe opposite was reported for transcription factor-eB(P=0.020),Plin2(P=0.003),Plin3(P=0.031),and Plin5(P=0.005)compared to the control *** was no significant difference between groups for lysosome-associated membrane proteins-2(P=0.715),rubicon(P=0.166),and Cd36(P=0.312).The intervention group showed a significant increase in miR-34a(P=0.005)and miR-21(P=0.043)compared to the *** was no significant difference between groups for miR-375(P=0.905),miR-26b(P=0.698),and miR-155(P=0.688).CONCLUSION Animals with MASH presented expression changes in markers related to lysosomal stress and autophagy as well as in miRNAs related to inflammation and fibrogenesis,processes that promote MASLD progression.

关键词： Animal model epigenetic Lipophagy MicroRNAs Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis

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Physics, chemistry, and Hirshfeld surface analyses of gamma-irradiated thalidomide to evaluate behavior under sterilization doses

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Journal of Pharmaceutical Analysis 2018年第3期8卷 194-201页

作者： Valner A.F.S.N.Mussel Max R Ferreira Maria B.e Marques Maria I.Yoshida Mariana R.Almeida Bernardo L.Rodrigues Wagner N.Mussel departamento de Quimica ICExUniversidade Federal de Minas Gerais-UFMGAv.Antonio Carlos 662731270-901 Belo HorizonteMGBrazil CNeN-CDTN Comissao Nacional de Energia Nuclear-Centro de Desenvolvimento da Tecnologia NuclearAv.Antonio Carlos6627 Belo HorizonteMGBrazil

Thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy （fourfold the usual sterilizing dose for pharmaceutics）. The polymorph of thalidomide was obtained in an isothermal experiment at 270℃. All samples underwent gamma irradiation for specific times. At different doses, decomposition of the pharmaceutical was not observed up to 100 kGy. The observed effect was angle turning between the phthalimide and glutarimide rings modulated by repulsion towards the carbonyl group, leading to a stable energetic configuration, as measured by the equilibrium in the torsion angle after irradiation. The thalidomide molecule has a center of symmetry, so a full turn starting from 57.3° will lead to an identical molecule. Further irradiation will start the process again. Samples irradiated at 30 and 100 kGy have more compact unit cells and a lower volume, which leads to an increase in the intermolecular hydrogen interaction within the unit cell, resulting in higher thermal stability for polymorph α.

关键词： Thalidomide Thermal stability Polymorphs Gamma irradiation Hirshfeld

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Litter production and leaf nutrient concentration and remobilization in response to climate seasonality in the central Amazon

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Journal of Forestry Research 2024年第3期35卷 131-141页

作者： Ricardo Antonio Marenco Saul Alfredo Antezana-Vera Daniela Pereira Dias Luiz Antonio Candido Instituto nacional de Pesquisas da Amazonia Coordenagao de Uso da Terra e Mudanca ClimaticaAv.Andre Araujo 2936ManausAM69067-375Brazil Programa de pos-Graduagao em Agricultura no Tropico Umido Instituto Nacional de Pesquisas da Amazonia-INPAManausAMBrazil Unidade Academica de Ciencias Agrarias Universidade Federal de JataiBR 364km 195JataiGO 75801-615Brazil

Litterfall is the largest source of nutrients to for-est soils of tropical ***,variability in lit-terfall production,nutrient remobilization,and changes in leaf nutrient concentration with climate seasonality remain largely unknown for the central *** study meas-ured litterfall production,leaf nutrient remobilization,and leaf area index on a forest plateau in the central *** was measured at monthly intervals during 2014,while nitrogen,phosphorus,potassium,calcium and mag-nesium concentrations of leaf litter and canopy leaves were measured in the dry and rainy seasons,and remobilization rates *** area index was also recorded in the dry and rainy *** litterfall varied from 33.2(in the rainy season)to 87.6 g m^(-2) in the dry season,while leaf area index increased slightly in the rainy *** seasonality had no effect on concentrations of nitrogen,calcium,and magnesium,whereas phosphorous and potassium responded to rainfall seasonality *** phosphorous increased,potassium decreased during the dry *** seasons,nitrogen,potassium,and phosphorous decreased in leaf litter;calcium increased in leaf litter,while magnesium remained unaffected with leaf ***,the five nutrients had similar remobilization rates over the *** absence of climate seasonality on nutrient remobilization suggests that the current length of the dry season does not alter nutrient remobilization rates but this may change as dry periods become more prolonged in the future due to climate change.

关键词： Throughfall Nutrient cycling Climatic seasonality Leaf mass per area

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Reconstruction of lithofacies using a supervised Self-Organizing Map:Application in pseudo-wells based on a synthetic geologic cross-section

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Artificial Intelligence in Geosciences 2024年第1期5卷 14-26页

作者： Carreira V.R. Bijani R. Ponte-Neto C.F. departamento de Geologia e Geofísica Universidade Federal Fluminense(UFF)NiteróiBrazil Coordenação de Geofísica Observatório Nacional(ON-MCTIC)Rio de JaneiroBrazil

Recently,machine learning(ML)has been considered a powerful technological element of different society *** transform the computer into a decision maker,several sophisticated methods and algorithms are constantly created and *** geophysics,both supervised and unsupervised ML methods have dramatically contributed to the development of seismic and well-log data *** well-logging,ML algorithms are well-suited for lithologic reconstruction problems,once there is no analytical expressions for computing well-log data produced by a particular rock ***,supervised ML methods are strongly dependent on a accurate-labeled training data-set,which is not a simple task to achieve,due to data absences or *** an adequate supervision is performed,the classification outputs tend to be more accurate than unsupervised *** work presents a supervised version of a Self-Organizing Map,named as SSOM,to solve a lithologic reconstruction problem from well-log ***,we go for a more controlled problem and simulate well-log data directly from an interpreted geologic *** then define two specific training data-sets composed by density(RHOB),sonic(DT),spontaneous potential(SP)and gamma-ray(GR)logs,all simulated through a Gaussian distribution function per *** the training data-set is created,we simulate a particular pseudo-well,referred to as classification well,for defining controlled *** one comprises a training data-set with no labeled log data of the simulated fault *** the second test,we intentionally improve the training data-set with the *** bespeak the obtained results for each test,we analyze confusion matrices,logplots,accuracy and *** from very thin layer misclassifications,the SSOM provides reasonable lithologic reconstructions,especially when the improved training data-set is considered for *** set of numerical experiments shows that our SSOM is extremely

关键词： Self-Organizing Maps Supervised machine learning Synthetic well-log data Classification of lithofacies

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