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Preclinical models of idiosyncratic drug-induced liver injury(idILI):Moving towards prediction

Acta Pharmaceutica Sinica B 2021年第12期11卷 3685-3726页

作者： Antonio Segovia-Zafra daniel E.di Zeo-Sanchez Carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-Fuentes Raul J.Andrade M.Isabel Lucena Marina Villanueva-paz Unidad de Gestio´n Clı´nica de Gastroenterologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Centro de Investigacion Biomedica en Red en el Area Tematica de Enfermedades Hepaticas y digestivas(CIBERehd) Madrid 28029Spain Platform ISCIII de Ensayos Clınicos UICEC-IBIMAMalaga 29071Spain Unidad de Gestion Clınica de Aparato digestivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induced liver injury(idILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the *** remains a major public health problem and a major cause of drug *** the lack of biomarkers for idILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of idILI is *** of the major limitations of idILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant ***,major advances in the understanding of idILI susceptibility and pathogenesis have come from the study of well-phenotyped idILI ***,there are many gaps for explaining all the complexity of idILI susceptibility and ***,there is a need to optimize preclinical human in vitro models to reduce the risk of idILI during drug ***,the current experimental models and the future directions in idILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal idILI *** also comment about in silico approaches and the increasing relevance of patient-derived cellular models.

关键词： drug-induced liver injury Preclinical models Mechanisms Oxidative stress Mitochondrial damage Immune response Personalized medicine

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Performance analysis of visual markers for indoor navigation systems

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Frontiers of Information Technology & Electronic Engineering 2016年第8期17卷 730-740页

作者： Gaetano C.LA dELFA Salvatore MONTELEONE Vincenzo CATANIA Juan F.dE paz Javier BAJO department of Electrical Electronics and Computer Engineering (DIEEI) University of Catania Catania 95125 Italy BISITE Research Group Faculty of Science University of Salamanca Salamanca 37007 Spain department of Artificial Intelligence Polytechnic University of Madrid Madrid 28660 Spain

The massive diffusion of smartphones, the growing interest in wearable devices and the Internet of Things, and the exponential rise of location based services（LBSs） have made the problem of localization and navigation inside buildings one of the most important technological challenges of recent years. Indoor positioning systems have a huge market in the retail sector and contextual advertising; in addition, they can be fundamental to increasing the quality of life for citizens if deployed inside public buildings such as hospitals, airports, and ***, in emergency situations, they can make the difference between life and death. Various approaches have been proposed in the literature. Recently, thanks to the high performance of smartphones＇ cameras, marker-less and marker-based computer vision approaches have been investigated. In a previous paper, we proposed a technique for indoor localization and navigation using both Bluetooth low energy（BLE） and a 2d visual marker system deployed into the floor. In this paper, we presented a qualitative performance evaluation of three 2d visual markers, Vuforia,Ar Uco marker, and AprilT ag, which are suitable for real-time applications. Our analysis focused on specific case study of visual markers placed onto the tiles, to improve the efficiency of our indoor localization and navigation approach by choosing the best visual marker system.

关键词： Indoor localization Visual markers Computer vision

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dagupan River Basin Exposure and Vulnerability Assessment of Buildings Extracted from LidAR derived datasets

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American Journal of Climate Change 2020年第4期9卷 454-479页

作者： Annie Melinda paz-Alberto Jo Adrianne A. Espiritu Kathrina Mapanao Institute for Climate Change and Environmental Management Central Luzon State University Science City of Mu&#241 oz Philippines

The Philippines has a geographical and geological setting of a typhoon-prone country. Tropical cyclones have a high incidence of passing through the Philippine islands during the months of September to November with an average time overland at 11 hours north of 14.5° contrasted to 20 hours south of 14.5°. due to the frequent occurrence of typhoons and tropical cyclones in this country, most of the provinces of the Philippines experience flood-related disasters that affect the people, their livelihood and many infrastructures. It is deemed necessary for the Philippines to come up with strategies to prevent further damage to its people and their properties. In this study, through the use of important parameters such as earth observations, Light detection and Ranging (LidAR) and Geographic Information System (GIS), assessment of buildings in dagupan, the Philippines with the possibility of being affected by floods during different typhoon scenarios was done. GIS overlay analysis of the CLSU Phil-LidAR 1 Project outputs, the 3d building GIS database, and flood hazard maps was done for the assessment. One (1) meter resolution LidAR digital Elevation Models (dEMs), geo-tagged video captured data and high-resolution images in Google Earth were used for processing and analysis to produce a 3d building GIS database. HEC HMS and HEC RAS were used to develop flood models that were used to produce flood hazard maps with different hazard levels. The results of this study were the series of flood exposure maps and vulnerability maps with statistics at different rainfall scenarios. Moreover, the buildings that will be affected by flood in the area were quantified and these were categorized according to their type. It was observed that as the rainfall return period increases, the number of buildings predicted to be exposed and vulnerable to flood also increases. The houses, business establis

关键词： Geographic Information System Flood database Extraction Hazard

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中性空位引起的本征扩散对硅中注入砷离子在退火过程中再分布的影响

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Journal of Semiconductors 1990年第8期11卷 642-645页

作者：汤庭鳌郑大卫 C.A.paz de Araujo 复旦大学电子工程系 University of Colorado at Colorado Springs USA

本文对硅中砷扩散系数考虑了中性空位引起的本征扩散项d^0的影响,推导而得出d^0对表面浓度N_s,结深x_j(t)等的影响大约为5-10％。在离子注入退火的解析模型中考虑其影响是有实际意义的。

关键词：离子注入硅砷离子退火本征扩散

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用数值法分析TF-SOI-MOS管沟道区的电势分布

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Journal of Semiconductors 1992年第12期13卷 736-741页

作者：汤庭鳌郑大卫黄宜平 C.A.paz de Araujo 复旦大学微电子所 University of Colorado Colorado SpringsU.S.A.CO 80933-7150

本文对 TF-SOI/MOS管,采取双栅极模型,用有限元和有限差分法分别求解沟道区的电势分布,得到了前栅(front gate)及背栅(back gate)MOS体电势二维分布.总结了指导TF-SOI-MOS 器件研制的要点.并对TF-SOI-MOS器件数值模拟方法进行了讨论.

关键词： MOS器件电热分布沟道区

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Two Approaches to the Study of a Controversial Relationship: Cutaneous Photosensitivity and Anti-Ro/SS-A Autoantibodies

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Open Journal of Rheumatology and Autoimmune diseases 2014年第1期4卷 1-12页

作者： Mariela L. paz Eliana M. Cela Alejandro Ferrari Adrián d. Friedrich Juliana Leoni daniel H. González Maglio Immunology department Pharmacy and Biochemistry School University of Buenos Aires Buenos Aires Argentina.

Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte’s surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TNF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation;and disagree with many other authors, who believe in the strong association between these two events.

关键词： Cutaneous Photosensitivity Purified Anti-Ro/SS-A Autoantibodies SKH-1 Hairless Mice UVB Irradiation TNF-α

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Intravenous vs intraperitoneal mesenchymal stem cells administration:What is the best route for treating experimental colitis?

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World Journal of Gastroenterology 2014年第48期20卷 18228-18239页

作者： Fabiany da Costa Goncalves Natália Schneider Fernanda Otesbelgue Pinto Fabíola Schons Meyer Fernanda Visioli Bianca Pfaffenseller Patrícia Luciana da Costa Lopez Eduardo Pandolfi Passos Elizabeth Obino Cirne-Lima Luíse Meurer Ana Helena paz Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre Porto Alegre 90035-903Rio Grande do SulBrazil Programa de Pós-Gradua??o:Ciências em Gastroenterologia e Hepatologia Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Faculdade de Odontologia Universidade Federado Rio Grande do SulPorto Alegre 90035-003Rio Grande doSulBrazil

AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of ***:MSCs were isolated from C57BL/6 mouse adipose *** cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular *** acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(dSS)in drinking water ad libitum from days 0 to *** mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and *** disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and *** compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological *** responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 *** rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UdPbiotin nick end labeling ***:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(Pducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and *** histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory *** therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in a

关键词： Ulcerative colitis dextran sulfate sodium Inflammatory bowel disease Mesenchymal stem cell Cell transplantation Intravenous injection Immunomodulation

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Temperature changes in the root ecosystem affect plant functionality

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Plant Communications 2023年第3期4卷 197-214页

作者： Mary paz González-García Carlos M.Conesa Alberto Lozano-Enguita Victoria Baca-González Bárbara Simancas Sara Navarro-Neila María Sánchez-Bermúdez Isai Salas-González Elena Caro Gabriel Castrillo Juan C.del Pozo Centro de Biotecnología y Genómica de Plantas(UPM-INIA/CSIC) Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agrariay Alimentaria-CSIC(INIA/CSIC)Campus Montegancedo28223 Pozuelo de Alarcón(Madrid)Spain departamento de Biotecnología-Biología Vegetal Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de Madrid(UPM)28040 MadridSpain Undergraduate Program in Genomic Sciences Center for Genomics SciencesUniversidad Nacional Autonóma de MéxicoAv.Universidad s/n.Col.ChamilpaCuernavaca 62210MorelosMéxico Future Food Beacon of Excellence&School of Biosciences University of NottinghamSutton BoningtonUK

Climate change is increasing the frequency of extreme heat events that aggravate its negative impact on plant development and agricultural *** experiments designed to study plant adaption to heat stress apply homogeneous high temperatures to both shoot and ***,this treatment does not mimic the conditions in natural fields,where roots grow in a dark environment with a descending temperature *** high temperatures severely decrease cell division in the root meristem,compromising root growth,while increasing the division of quiescent center cells,likely in an attempt to maintain the stem cell niche under such harsh ***,we engineered the TGRooZ,a device that generates a temperature gradient for in vitro or greenhouse growth *** root systems of plants exposed to high shoot temperatures but cultivated in theTGRooZ grow efficiently and maintain their functionality to sustain proper shoot growth and ***,gene expression and rhizosphere or root microbiomecomposition are significantly less affected in TGRooZ-grown roots than in high-temperature-grown roots,correlating with higher root *** data indicate that use of the TGRooZ in heat-stress studies can improve our knowledge of plant response to high temperatures,demonstrating its applicability from laboratory studies to the field.

关键词： heat stress root temperature gradient nutrition gene expression microbiome

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Biopolymer Sponge for High Grade Renal Trauma: An Experimental Study in Rabbits

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Open Journal of Urology 2014年第1期4卷 1-6页

作者： Leandro H. M. Tavares Fábio O. Vilar José L. Aguiar Alexandre R. paz Francisco A. d. Melo Gustavo R. P. Negromonte department of Surgery Federal University of Paraiba University Hospital Lauro Wanderley Joao Pessoa Brazil department of Surgery Federal University of Pernambuco Clinics Hospital Recife Brazil

Introduction: Acute blunt or open renal trauma sometimes requires conservative measure which involves the use of specific materials in order to adequately restore renal parenchima. The purpose of this study is to analyze the effects of the sugar cane biopolymer sponge in an experimental model of renal trauma in rabbits. Methods: Experimental prospective study was paired with twelve New Zealand rabbits. After induction of renal trauma bilateral high-grade (grade 4-collecting system, according to AAST), the sugar cane biopolymer sponge was used for homeostasis and reconstruction of the right renal parenchyma (experimental group). The same procedure was performed in the left kidney, but using the Surgifoam? sponge (Control Group). The animals were sacrificed after four weeks. Histological analysis was performed and the results were compared after statistically being evaluated. Results: Comparing the experimental group with the control, there was more inflammatory reaction and premature adhesions in the first one. Concerning the influence on efficacy and biocompatibility of the biopolymer, no serious complications like massive bleeding, haematoma, fistula or urinary stone formation were found in both groups. Conclusion: The sugar cane biopolymer sponge demonstrated good efficacy in relation to hemostatic control and reconstruction of the renal parenchyma without major complications. Future studies may direct its routine use in urologic practice.

关键词： Acute Renal Injury Surgical Hemostasis Absorbable Implants Inflammation Biocompatible Materials

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Hepatic lipid metabolism changes in short-and long-term prehepatic portal hypertensive rats

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World Journal of Gastroenterology 2006年第42期12卷 6828-6834页

作者： Maria-Angeles Aller Elena Vara Cruz García Maria-paz Nava Alejandra Angulo Fernando Sánchez-Patán Ana Calderón Patri Vergara Jaime Arias SurgeryⅠ department School of Medicine Complutense University of Madrid Spain Biochemical and Molecular Biology department School of Medicine Complutense University of Madrid Spain Animal Physiology department (Physiology Ⅱ) School of Biological Sciences Complutense University of Madrid Spain Physiology Unit. Veterinary School Autonoma University of Barcelona Bellaterra Catalua Spain

AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHOdS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using d-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P d was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P d metabolism. This impairment consists in an increase in lipid deposits (triglycerides,diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.

关键词： Portal hypertension Free fatty acids diacylglycerides Triglycerides Phospholipids Cholesterol

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