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Repurposing drugs to target nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2019年第15期25卷 1783-1796页

作者： Silvia Sookoian carlos J Pirola Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council (CONICET) University of Buenos Aires Institute of Medical Research (IDIM) Department of Molecular Genetics and Biology of Complex Diseases National Scientific and Technical Research Council (CONICET) University of Buenos Aires Institute of Medical Research (IDIM)

Nonalcoholic fatty liver disease(NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack of approved pharmacological interventions for the treatment of nonalcoholic steatohepatitis(NASH) and NASH-fibrosis-the severe histological forms. Over the past decade,tremendous advances have been made in NAFLD research, resulting in the discovery of disease mechanisms and novel therapeutic targets. Hence, a large number of pharmacological agents are currently being tested for safety and efficacy. These drugs are in the initial pharmacological phases(phase 1 and 2),which involve testing tolerability, therapeutic action, and pharmacological *** is thus reasonable to assume that the next generation of NASH drugs will not be available for clinical use for foreseeable future. The expected delay can be mitigated by drug repurposing or repositioning, which essentially relies on identifying and developing new uses for existing drugs. Here, we propose a drug candidate selection method based on the integration of molecular pathways of disease pathogenesis into network analysis tools that use OMICs data as well as multiples sources, including text mining from the medical literature.

关键词： Drug discovery Drug repositioning Fibrosis Genetics Treatment Systems biology

A building energy models calibration methodology based on inverse modelling approach

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Building Simulation 2022年第11期15卷 1883-1898页

作者： Vicente Gutiérrez González carlos Fernández Bandera Installations construction and structuresSchool of ArchitectureUniversity of NavarraCampus UniversitarioPamplona31009NavarraSpain

Nowadays,building energy models(BEMs)are widely used,particularly in the assessment of energy consumption in buildings to address the potential savings that can be *** realisation of a dynamic energy model based on high-fidelity physics(white-box models)requires a tuning process to fit the model to reality,due to many uncertainties *** some research trends try to reduce this performance gap by modulating different types of experimental parameters such as:capacitances or *** EnergyPlus simulation software,in its latest versions,has implemented an object:HybridModel:Zone that calculates the infiltration and internal mass of buildings using an inverse modelling approach that employs only the measured indoor temperature data to invert the heat balance equation for the zone under *** main objective of this paper is to reduce the execution time and uncertainties in the development of quality energy models by generating a new calibration methodology that implements this *** uses,as a starting point,a research created by the authors of this study,which was empirically and comparatively validated against the energy models developed by the participants in Annex *** is also worth highlighting the empirical validation of the HybridModel:Zone object,since it was activated in all scenarios where its execution is possible:periods of seven days or more of free oscillation and periods in which the building is under *** findings are *** data generated with the new methodology,if compared with those produced by the baseline model,improve their resemblance to the real ones by 22.9%.While those of its predecessor did it by 15.6%.For this study,the two dwellings foreseen in Annex 58 of the IEA ECB project have been modelled and their real monitoring data have been used.

关键词： internal thermal mass energy simulation EnergyPlus inverse model Annex 58 infiltration

Kinetic approach to the study of froth flotation applied to a lepidolite ore

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International Journal of Minerals,Metallurgy and Materials 2016年第7期23卷 731-742页

作者： Nathália Vieceli Fernando O.Durao carlos Guimaraes carlos A.Nogueira Manuel F.C.Pereira Fernanda Margarido Center for Innovation Technology and Policy Research-IN+Instituto Superior T6cnicoUniversity of Lisbon1049-001 LisboaPortugal CERENA-Centro de Recursos Naturais e Ambiente DECivilInstituto Superior TecnicoUniversity of Lisbon1049-001 LisboaPortugal LNEG-Laboratorio Nacional de Energia e Geologia I.P.Campus do Lumiar1649-038 LisboaPortugal

The number of published studies related to the optimization of lithium extraction from low-grade ores has increased as the demand for lithium has grown. However, no study related to the kinetics of the concentration stage of lithium-containing minerals by froth flotation has yet been reported. To establish a factorial design of batch flotation experiments, we conducted a set of kinetic tests to determine the most selective alternative collector, define a range of pulp p H values, and estimate a near-optimum flotation time. Both collectors（Aeromine 3000 C and Armeen 12D） provided the required flotation selectivity, although this selectivity was lost in the case of pulp p H values outside the range between 2 and 4. Cumulative mineral recovery curves were used to adjust a classical kinetic model that was modified with a non-negative parameter representing a delay time. The computation of the near-optimum flotation time as the maximizer of a separation efficiency（SE） function must be performed with caution. We instead propose to define the near-optimum flotation time as the time interval required to achieve 95%–99% of the maximum value of the SE function.

关键词： lepidolite lithium ore treatment froth flotation kinetic analysis

Effects of precipitation changes on the dynamics of sparse elm woodland in Northeastern China

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BIOCELL 2018年第2期42卷 61-66页

作者： Yi TANG carlos Alberto BUSSO School of Life Science Liaoning UniversityNo.66 Chongshan RoadShenyang(C.P.110036)Liaoning ProvinceChina Departamento de Agronomía-CERZOS(CONICET) Universidad Nacional del Sur8000 Bahía BlancaArgentina

Elm(Ulmus pumila L.)is the dominant tree species in the sparse elm woodland,the original vegetation in the Horqin Sandy *** effects of changes in precipitation on *** trees have not been fully *** determined a dynamic model by considering the five stages in the *** life cycle,***,seedling,and juvenile,mature and over-mature tree *** effects of changes in precipitation on population density and age structure were then *** density,after averaging all study developmental morphology stages,ranged from 16.67 individuals/m2 to 25.01 individuals/m2 under a mean annual precipitation(MAP)of 80%to 120%,*** suggests that population density could increase as MAP also *** proportion of seedlings,and juvenile,mature and over-mature trees were 95.23%,4.58%,0.19%and 0.01%,respectively,under all precipitation *** indicates that precipitation had little effects on the developmental stages of the studied *** populations in the Horqin Sandy *** water supply might be provided in addition to the natural rainfall that occurs in the region,for contributing to maintain *** population density in the Horqin Sandy Land.

关键词： Population density Precipitation Semi-arid lands System dynamics model

Queering Time： Disjunctive Temporalities in Modern China

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Frontiers of Literary Studies in China-Selected Publications from Chinese Universities 2016年第1期10卷 1-8页

作者： carlos Rojas Duke University

Responding to the popular 2011 television miniseries Palace （Gong 宫）, about a contemporary woman who travels back in time and finds herself in a love triangle with two handsome Qing dynasty princes, China＇s State Administration of Radio, Film, and Television （SARFT） issued a now-famous directive noting that works like Palace ＂casually make up myths, have monstrous and weird plots, use absurd tactics, and even promote feudalism, superstition, fatalism and reincarnation.＂ The directive concludes ominously that these works ＂should no longer be encouraged＂.

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Liver enzymes,metabolomics and genome-wide association studies:From systems biology to the personalized medicine

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World Journal of Gastroenterology 2015年第3期21卷 711-725页

作者： Silvia Sookoian carlos J Pirola Department of Clinical and Molecular Hepatology Institute of Medical Research A Lanari-IDIMUniversity of Buenos Aires-National Scientific and Technical Research Council Ciudad Autónoma de Buenos AiresBuenos Aires 1427Argentina Department of Molecular Genetics and Biology of Complex Diseases Institute of Medical Research A Lanari-IDIMUniversity of Buenos Aires-National Scientific and Technical Research CouncilCiudad Autónoma de Buenos AiresBuenos Aires 1427Argentina

For several decades,serum levels of alanine(ALT) and aspartate(AST) aminotransferases have been regarded as markers of liver injury,including a wide range of etiologies from viral hepatitis to fatty *** increasing worldwide prevalence of metabolic syndrome and cardiovascular disease revealed that transaminases are strong predictors of type 2 diabetes,coronary heart disease,atherothrombotic risk profile,and overall risk of metabolic ***,it is plausible to suggest that aminotransferases are surrogate biomarkers of "liver metabolic functioning" beyond the classical concept of liver cellular damage,as their enzymatic activity might actually reflect key aspects of the physiology and pathophysiology of the liver *** this study,we summarize the background information and recent findings on the biological role of ALT and AST,and review the knowledge gained from the application of genome-wide approaches and "omics" technologies that uncovered new concepts on the role of aminotransferases in human diseases and systemic regulation of metabolic *** of biomolecular interactions between the candidate genes recently discovered to be associated with plasma concentrations of liver enzymes showed interesting interconnectivity nodes,which suggest that regulation of aminotransferase activity is a complex and highly regulated ***,links between aminotransferase genes and metabolites are explored to understand the genetic contributions to the metabolic diversity.

关键词： Transaminases Aminotransferases Alanineaminotransf

An Efficient Real Space Method for Orbital-Free Density-Functional Theory

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Communications in Computational Physics 2007年第2期2卷 334-357页

作者： carlos J.Garcıa-Cervera Department of Mathematics University of CaliforniaSanta BarbaraCA 93106USA.

We consider the Thomas-Fermi-von Weizsacker energy functional,with the Wang-Teter correction,and present an efficient real space method for Orbital-Free Density Functional *** is proved that the energy minimizer satisfies a second order quasilinear elliptic equation,even at the points where the electron density *** information is used to construct an efficient energy minimization method for the resulting constrained problem,based on the truncated Newton method for unconstrained *** Wang-Teter kernel is analyzed,and its behavior in real space at short and far distances is determined.A second order accurate discretization of the energy is obtained using finite *** efficiency and accuracy of the method is illustrated with numerical simulations in an Aluminium FCC lattice.

关键词： Density functional theory truncated Newton method constrained optimization.

＂Symptom of an Era＂： Dung Kai-Cheung＇s Histories of Time

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Frontiers of Literary Studies in China-Selected Publications from Chinese Universities 2016年第1期10卷 133-149页

作者： carlos Rojas Asian Pacific Studies Institute Duke University John Hope Franklin Center 2204 Erwin RoadDurham NC 27708-0411 USA

This essay uses the notion of a symptom to examine the ways in which temporality is deployed in Hong Kong author Dung Kai-Cheung＇s 2007 novel, Histories o^Time. In particular, the essay follows Dung＇s own lead, in Histories of Time, and considers the peculiar temporality implicit in the concept of figuration in Biblical hermeneutics, wherein the ＂figure＂ mediates between the two distinct--yet structurally related--temporalities of the Old and the New Testaments： the ＂prefiguration＂ of the Old Testament and the ＂fulfillment of figuration＂ of the New Testament. I propose that a literary ＂figure,＂ in Dung＇s work, similarly mediates between the different temporal planes within his novel, while at the same time mediating between the fictional space of the novel and the historical era within which the work is positioned. Just as a symptom is simultaneously a function of--but also structurally external to--the underlying condition that it signifies, this sort of literary figure may similarly be seen as a function of--but simultaneously external to--the historical era to which it corresponds. This sort of literary figure, accordingly, marks a point of rupture within the temporality of the novel and its corresponding era, while at the same time providing the ground on which that temporal continuum is established in the first place.

关键词： Dung Kai-Cheung Histories of Time symptom figuration Hong Kong

Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

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World Journal of Gastroenterology 2018年第15期24卷 1601-1615页

作者： carlos J Pirola Silvia Sookoian Department of Genetics and Molecular Biology of Complex Diseases. University of Buenos Aires Institute of Medical Research A Lanari Buenos Aires Argentina National Scientific and Technical Research Council-University of Buenos Aires. Institute of Medical Research (IDIM) Clinical and Molecular Hepatology University of Buenos Aires Institute of Medical Research A Lanari Buenos Aires Argentina National Scientific and Technical Research Council-University of Buenos Aires. Institute of Medical Research (IDIM)

This review intends to uncover how information from large-scale genetic profiling(whole genome sequencing, and whole exome sequencing) of nonalcoholic fatty liver disease(NAFLD), as well as information from circulating transcriptomics(cell-free mi RNAs) and metabolomics, contributes to the understanding of NAFLD pathogenesis. A further aim is to address the question of whether OMICs information is ready to be implemented in the clinics. The available evidence suggests that any new knowledge pertaining to molecular signatures associated with NAFLD and nonalcoholic steatohepatitis should be promptly translated into the clinical setting. Nevertheless, rigorous steps that must include validation and replication are mandatory before utilizing OMICs biomarkers in diagnostics to identify patients at risk of advanced disease, including liver cancer.

关键词： nonalcoholic steatohepatitis Fibrosis Liver biopsy Genetics PNPLA3 TM6SF2 Metabolomics Proteomics Transcriptomics nonalcoholic fatty liver disease miR122