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Alcoholic liver disease:Utility of animal models

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World journal of Gastroenterology 2018年第45期24卷 5063-5075页

作者： Arantza Lamas-Paz Fengjie Hao leonard j nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for Bioengineering(IBioE) School of EngineeringFaraday BuildingThe University of EdinburghEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Human Anatomy and Embryology Complutense University School of MedicineMadrid 28040Spain Instituto de Neurociencias Consejo Superior de Investigaciones CientíficasUniversidad Miguel HernándezSan Juan de Alicante 03550Spain Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain Department of Genetics Physiology and MicrobiologyFaculty of BiologyUniversidad ComplutenseMadrid 28040Spain Department of Internal Medicine Ⅲ University Hospital RWTH AachenAachen 52062Germany

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

关键词： Steatohepatitis Cirrhosis Hepatocellular carcinoma Alcoholic liver disease Reactive oxygen species

Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications

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Nano-Micro Letters 2024年第3期16卷 1-35页

作者： Sourav Dutta Seungmin Noh Roger Sanchis Gual Xiangzhong Chen Salvador Pané Bradley j.nelson Hongsoo Choi Department of Robotics and Mechatronics Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)Daegu 42988Republic of Korea DGIST‑ETH Microrobotics Research Center DGISTDaegu 42988Republic of Korea Multi‑Scale Robotics Lab Institute of Robotics and Intelligent SystemsETH Zurich8092 ZurichSwitzerland Institute of Optoelectronics State Key Laboratory of Photovoltaic Science and TechnologyShanghai Frontiers Science Research Base of Intelligent Optoelectronics and PerceptionFudan UniversityShanghai 200433People’s Republic of China

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation.Metal-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen bubbles.This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications.In addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance.Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor.Here we review the design and recent advancements of metallic degradable micromotors.Furthermore,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications.Moreover,we discuss micromotors’efficacy in detecting and destroying environmental pollutants.Finally,we address the limitations and future research directions of degradable metallic micromotors.

关键词： Magnesium Zinc Iron Biodegradable microrobot Biomedical Environmental

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

Determining the effective elastic thickness through cross-correlation between isostatic disturbances

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Geodesy and Geodynamics 2024年第3期15卷 241-251页

作者： nelson Ribeiro-Filho Cristiano Mendel Martins Raissa Moraes Baldez Ivaldevingles Rodrigues de Souza júnior Franck Eitel Kemgang Ghomsi Instituto Federal do Pará(IFPA) AltamiraParáBrazil Universidade Federal do Pará(UFPA) BelemParáBrazil Nansen-Tutu Center for Marine Environmental Research Department of OceanographyUniversity of Cape TownSouth Africa Geodesy Research Laboratory National Institute of CartographyYaoundeCameroon

The elastic thickness parameter was estimated using the mobile correlation technique between the observed isostatic disturbance and the gravity disturbance calculated through direct gravimetric modeling. We computed the vertical flexure value of the crust for a specific elastic thickness using a given topographic dataset. The gravity disturbance due to the topography was determined after the calculation. A grid of values for the elastic thickness parameter was generated. Then, a moving correlation was performed between the observed gravity data(representing actual surface data) and the calculated data from the forward modeling. The optimum elastic thickness of the particular point corresponded to the highest correlation coefficient. The methodology was tested on synthetic data and showed that the synthetic depth closely matched the original depth, including the elastic thickness value. To validate the results, the described procedure was applied to a real dataset from the Barreirinhas Basin, situated in the northeastern region of Brazil. The results show that the obtained crustal depth is highly correlated with the depth from known models. Additionally, we noted that the elastic thickness behaves as expected, decreasing from the continent towards the ocean. Based on the results, this method has the potential to be employed as a direct estimate of crustal depth and elastic thickness for any region.

关键词： Isostasy Elastic thickness Isostatic disturbance Moho depth Cross-correlation

A neural branch-and-price for truck scheduling in cross-docks

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Science China Mathematics 2024年第6期67卷 1341-1358页

作者： Rahimeh Neamatian Monemi Shahin Gelareh nelson Maculan Wei-Kun Chen Sharkey Predictim Globe Villeneuve d’Ascq59650France Département R&T IUT de BéthuneUniversitéd’ArtoisBéthuneF-62000France Federal University of Rio de janeiro COPPE-PESCRio de JaneiroRJ 21941-972Brazil School of Mathematics and Statistics Beijing Institute of TechnologyBeijing100081China

In this paper,we address the complex problem of dock-door assignment and truck scheduling within cross-docking operations.This is a problem that requires frequent resolution throughout the operational day,as disruptions often invalidate the optimal plan.Given the problem's highly combinatorial nature,finding an optimal solution demands significant computational time and resources.However,the distribution of data across problem instances over a lengthy planning horizon remains consistently stable,with minimal concern regarding distribution shift.These factors collectively establish the problem as an ideal candidate for a learn-to-optimize solution strategy.We propose a Dantzig-Wolfe reformulation,solving it via both a conventional branch-and-price approach and a neural branch-and-price approach,the latter of which employs imitation learning.Additionally,we introduce some classes of valid inequalities to enhance and refine the pricing problem through a branch-and-cut scheme.Our computational experiments demonstrate that this methodology is not only feasible but also presents a viable alternative to the traditional branch-and-price algorithms typically utilized for such challenges.

关键词： cross-docking MILP modeling Dantzig-Wolfe decomposition graph convolutional network

The Cloud Model for Climate Change

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International journal of Geosciences 2024年第5期15卷 366-395页

作者： Michael nelson David B. nelson Retired Pleasanton CA USA

In 1995, the Intergovernmental Panel on Climate Change (IPCC) released a thermodynamic model based on the Greenhouse Effect, aiming to forecast global temperatures. This study delves into the intricacies of that model. Some interesting observations are revealed. The IPCC model equated average temperatures with average energy fluxes, which can cause significant errors. The model assumed that all energy fluxes remained constant, and the Earth emitted infrared radiation as if it were a blackbody. Neither of those conditions exists. The IPCC’s definition of Climate Change only includes events caused by human actions, excluding most causes. Satellite data aimed at the tops of clouds may have inferred a high Greenhouse Gas absorption flux. The model showed more energy coming from the atmosphere than absorbed from the sun, which may have caused a violation of the First and Second Laws of Thermodynamics. There were unexpectedly large gaps in the satellite data that aligned with various absorption bands of Greenhouse Gases, possibly caused by photon scattering associated with re-emissions. Based on science, we developed a cloud-based climate model that complied with the Radiation Laws and the First and Second Laws of Thermodynamics. The Cloud Model showed that 81.3% of the outgoing reflected and infrared radiation was applicable to the clouds and water vapor. In comparison, the involvement of CO2 was only 0.04%, making it too minuscule to measure reliably.

关键词： Climate Change Greenhouse Gas CO2 Clouds Model Thermodynamics

Decoupling CO₂ from Climate Change

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International journal of Geosciences 2024年第3期15卷 246-269页

作者： Michael nelson David B. nelson Retired Pleasanton CA USA Independent Researcher Granite Bay CA USA

This study determines if there is a correlation between rising carbon dioxide levels and global warming. Historical data were reviewed from three different time periods spanning 500 million years. It showed that the curves and trends were too dissimilar to establish a connection. Observations from CO2/temp ratios showed that the CO2 and the temperature moved in opposite directions 42% of the time. Many ratios displayed zero or near zero values, reflecting a lack of response. As much as 87% of the ratios revealed negative or near zero values, which strongly negate a correlation. The infrared spectra showed the Greenhouse Gases had an exceptionally low absorption band between 11.67 μm to 9.1 μm, which is a zone called the infrared atmospheric window. Most of the Greenhouse Gases absorb little infrared inside that zone. And that zone is where the Earth’s surface emits almost all infrared radiation. Even with minimal absorbance, water vapor captures the most infrared radiation. It absorbs 84 times more than CO2, 407 thousand times more than methane, 452 thousand times more than ozone and 2.3 million times more than nitrous oxide. The Intergovernmental Panel on Climate Change (IPCC) and the United States EPA excluded water vapor because it was not associated with man-made activities. They reported that water vapor and clouds were simply feedback mechanisms from CO2. Clouds reflect radiation from the sun. The Northern Hemisphere is 2.7°F warmer than the Southern Hemisphere because of clouds. The world cloud cover has gone down 4.1% from 1982 to 2018. Calculations show that this could be responsible for 2.4°F of the 2.7°F. The research shows that most of the recent increase in temperature (89.9%) is because of fewer clouds.

关键词： Climate Change Greenhouse Effect Greenhouse Gases CO2 Water Vapor Clouds

Decoding complexity: the need to enhance precision and streamline spatial understanding in neuroscience

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Neural Regeneration Research 2025年第3期20卷 801-802页

作者： Sameehan Mahajani Armita Salahi Brenda Gonzalez Charlotte nelson Frank Hsiung Biology&Applications Division NodexusSan JoseCAUSA

Neuroscience is the ultimate frontier in our quest for a comprehensive understanding of human behavior. Since its launch in 2009, the Human Connectome Project has emerged as a pioneering force, making heroic strides i... 详细信息

关键词： behavior frontier dating

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed

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Infectious Diseases of Poverty 2024年第1期13卷 85-89页

作者： Robert Colebunders joseph nelson Siewe Fodjo Olivia Kamoen Luis-jorge Amaral Amber Hadermann Chiara Trevisan Mark j.Taylor julia Gauglitz Achim Hoerauf Yasuaki Sato Katja Polman Maria-Gloria Basanez Dan Bhwana Thomson Lakwo Gasim Abd-Elfarag Sebastien D.Pion Global Health Institute University of AntwerpAntwerpBelgium Department of Neurology Heilig Hart ZiekenhuisLierBelgium Department of Public Health Institute of Tropical MedicineAntwerpBelgium Liverpool School of Tropical Medicine LiverpoolUK Department of Computer Science University of AntwerpAntwerpBelgium Institute of Medical Microbiology Immunology and ParasitologyUniversity Hospital BonnBonnGermany German Center for Infection Research(DZIF) Partner Site Bonn-CologneBonnGermany School of Global Humanities and Social Sciences Nagasaki UniversityNagasakiJapan MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected TropicalDisease Research Department of Infectious Disease EpidemiologySchool of Public HealthImperial College LondonLondonUK National Institute for Medical Research TangaTanzania Vector Control Division Ministry of HealthKampalaUganda School of Public Health University of JubaJubaSouth Sudan Access for Humanity JubaSouth Sudan French National Research Institute for Sustainable Development MontpellierFrance

Background There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures,reinforcing the concept of onchocerciasis-associated epilepsy(OAE).The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem.Main text During the 2nd International Workshop on OAE held on 19-21 September,2023,in Antwerp,Belgium,participants recognised OAE as a substantial yet neglected public health problem,particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic.Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence.There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care t is expected that raising awareness about OAE will boost the population uptake of ivermectin.The implementation of a commu-nity-based epilepsy treatment programme offering free anti-seizure medications(ASMs)has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy.Conclusions To reduce OAE burden,enhanced collaboration between onchocerciasis and mental health pro-grammes at community,national,and international levels is required.Urgent efforts are needed to ensure the uninter-rupted provision of free ASMs in onchocerciasis-endemic areas.Furthermore,OAE should be included in the quantif-cation of the onchocerciasis disease burden.

关键词： Onchocerciasis Morbidity Burden of disease Prevention Ivermectin Epilepsy Nodding syndrome Treatment Children Policy