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Modeling tuberous sclerosis complex with human induced pluripotent stem cells

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World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu benjamin Siciliano Zhexing Wen Department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in Molecular and Systems Pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA Department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA Department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and ***,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum *** in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling *** models have been widely used to study the effect of TSCl/2 genes on the development and function of the *** considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human *** sources Literature reviews and research articles were published in PubMed-indexed *** Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human *** In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

Effect of thermo-mechanical conditions during constrained friction processing on the particle refinement of AM50 Mg-alloy phases

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Journal of Magnesium and Alloys 2024年第6期12卷 2298-2311页

作者： Camila Caroline de Castro AndréMartins Neves benjamin Klusemann Helmholtz-Zentrum Hereon Institute of Material and Process DesignSolid-State Materials Processing21502 GeesthachtGermany Helmholtz-Zentrum Hereon Institute of Hydrogen TechnologySystem Design for Mobility21502 GeesthachtGermany Helmut Schmidt University/University of the German Federal Armed Forces Hamburg Department of Mechanical and Civil Engineering22043 HamburgGermany Leuphana University Lüneburg Institute for Production Technology and Systems21335 LüneburgGermany

Constrained Friction Processing(CFP)is a novel solid-state processing technique suitable for lightweight materials,such Mg-and *** technique enables grain size refinement to fine or even ultrafine *** this study,the effect of CFP on the microstructural refinement of AM50 rods is investigated in terms of particle size and morphology of the eutectic and secondary phases originally present in the base material,in particular the eutecticβ-Mg_(17)Al_(12)and Al-Mn *** that purpose,as-cast and solution heat-treated base material and processed samples were *** Al8Mn5 intermetallic phase was identified as the main secondary phase present in all samples before and after the processing.A notorious refinement of these particles was observed,starting from particles with an average equivalent length of a few micrometers to around 560 nm after the *** refinement of the secondary phase refinement is attributed to a mechanism analogous to the attrition comminution,where the combination of temperature increase and shearing of the material enables the continuous breaking of the brittle intermetallic particles into smaller *** for the eutectic phase,the results indicate the presence of the partially divorcedβ-Mg_(17)Al_(12)particles exclusively in the as-cast base material,indicating that no further phase transformations regarding the eutectic phase,such as dynamic precipitation,occurred after the *** the case of the processed as-cast material analyzed after the CFP,the thermal energy generated during the processing led to temperature values above the solvus limit of the eutectic phase,which associated with the mechanical breakage of the particles,enabled the complete dissolution of this ***,CFP was successfully demonstrated to promote an extensive microstructure refinement in multiple aspects,in terms of grain sizes of theα-Mg phase and presence and morphology of the Al-Mn and eutecticβ-Mg_(17)Al_(12).

关键词： Constrained friction processing AM50 Refill friction stir spot welding Extrusion β-Mg_(17)Al_(12) Al-Mn phases

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Analysis of synthetic parameters for coating aluminum powders with phenyltriethoxysilane coupling agent and their effects on powder flow behavior

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Particuology 2024年第7期90卷 412-417页

作者： Lillian M.Mawby Bellamarie Ludwig benjamin J.Lear Department of Chemistry The Pennsylvania State UniversityUniversity ParkPA16802USA Applied Research Laboratory The Pennsylvania State UniversityUniversity ParkPA16802USA

Though silanization of aluminum powder is currently used to improve its flow properties,for use as an alternative fuel source,there are a wide range of experimental parameters for the process and not all of them have been thoroughly *** this is complete,it is unknown if the process is optimized in terms of time,efficiency,and ***,we report on a study into the effects of changes in humidity,degree of agitation,reaction temperature,and curing time upon the deposition of phenyl triethoxysilane into 20μm(d50)aluminum *** confirm the deposition of the coating via diffuse reflectance infrared spectroscopy and x-ray photoelectron *** then characterize the coated particles using apparent density measurements and Carney flow *** analysis of variance,we find that,of the parameters explored,only changes in cure time and reaction temperature provide meaningful changes to the apparent density,while none of our parameters produced statistically significant changes in Carney flow ***,we conclude that,when optimizing silanization of aluminum particles,environmental control of humidity is unneeded and that the reaction can be run with minimal *** ability to largely ignore these parameters is a benefit to large-scale processing.

关键词： Aluminum powder Silane Fluidization Apparent density Carney flow

Laser-induced plasma formation in water with up to 400 mJ double-pulse LIBS

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Plasma Science and Technology 2024年第1期26卷 93-100页

作者： Marion HENKEL Michelle SIEMENS Ralf METHLING benjamin EMDE Jörg HERMSDORF Steffen FRANKE Diego GONZALEZ Leibniz Institute for Plasma Science and Technology(INP) Felix-Hausdorff-Straße 2Greifswald 17489Germany Laser Zentrum Hannover e.V.(LZH) Hollerithallee 8Hannover 30419Germany

Double-pulse LIBS is a promising technique for deep-sea *** measurements in shallow water with up to 400 mJ each pulse were done to select laser parameters which promote optimized spectral line emission from plasma even at elevated pressures,where line broadening until loss of most of the spectral information can *** emission spectroscopy,using a Czerny-Turner spectrometer,has been applied to investigate the dependence of the emitted radiation on laser parameters and hydrostatic *** has been found,that higher laser pulse energies,especially with short pulse delay as required in high water pressure,can also have an adverse effect on the measured spectrum.

关键词： double-pulse LIBS underwater plasma formation emission spectrosocpy

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Floating plants reduced methane fluxes from wetlands by creating a habitat conducive to methane oxidation

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Journal of Environmental Sciences 2024年第1期135卷 149-160页

作者： Fuwei Wang Songhe Zhang Xiuren Hu Xin Lv Min Liu Yu Ma benjamin Manirakiza Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes Ministry of EducationHohai UniversityNanjing 210098China College of Environment Hohai UniversityNanjing 210098China China Machinery International Engineering Desigh and Research Institute co. Ltd.East China Regional CenterNanjing 210008China

Wetlands are one of the important natural sources of atmospheric methane (CH_4),as an important part of wetlands,floating plants can be expected to affect methane ***,the effects of floating plants on methane release are *** this study,methane fluxes,physiochemical properties of the overlying water,methane oxidation potential and rhizospheric bacterial community were investigated in simulated wetlands with floating plants Eichhornia crassipes,Hydrocharis dubia,and Trapa *** found that ***,***,and *** plants could inhibit 84.31%-97.31%,4.98%-88.91%and 43.62%-92.51%of methane fluxes at interface of water-atmosphere compared to Control,*** fluxes were negatively related to nutrients concentration in water column but positively related to the aerenchyma proportions of roots,stems,and *** the same biomass,root of *** (36.44%) had the highest methane oxidation potential,followed by *** (12.99%) and *** (11.23%).Forty-five bacterial phyla in total were identified on roots of three plants and 7 bacterial genera (2.10%-3.33%) were known *** I methanotrophs accounted for 95.07%of total *** pmoA gene abundances ranged from 1.90×10^(16)to 2.30×10^(18)copies/g fresh weight of root *** of pmoA gene was significantly positively correlated with environmental *** (5.40%) and methanotrophy (3.75%) function were closely related to methane *** study highlights that floating plant restoration can purify water and promote carbon neutrality partially by reducing methane fluxes through methane oxidation in wetlands.

关键词： Floating plants Methane fluxes Aerenchyma Methanotrophs

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Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

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Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon benjamin G.Chousterman Tomasz Skirecki Institut Pasteur ParisFrance Department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance Inserm U942 University of ParisParisFrance Department of Translational Immunology and Experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

The role of melatonin receptor 1B gene(MTNR1B)in the susceptibility to depression and type 2 diabetes comorbidity

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Genes & Diseases 2024年第3期11卷 113-115页

作者： Mutaz Amin benjamin Rafla Rongling Wu Teodor T.Postolache Cclaudia Gragnoli INSERM US14-OrphanetParis 75014France Department of Biochemistry and Molecular Biology Faculty of MedicineAl-Neelain UniversityKhartoum 11121Sudan Division of Endocrinology Department of MedicineCreighton University School of MedicineOmahaNE 68124USA Department of Public Health Sciences Penn State College of MedicineHersheyPA 17033USA Department of Statistics Penn State College of MedicineHersheyPA 17033USA Mood and Anxiety Program Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreMD 21201USA Rocky Mountain Mental llness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)19Military and Veteran Microbiome:Consortium for Research and Education(MVM-CoRE)DenverCO 80246USA Mental Ilness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)5VA Capitol Health Care NetworkBaltimoreMD 21090USA Molecular Biology Laboratory Bios Biotech Multi-Diagnostic Health CenterRome00197Italy

Melatonin is an endogenous monoamine hormone secreted by the pineal *** signaling has been shown to play a role in circadian rhythm regulation,lipid and glucose metabolism,and obesity,and it has anti-inflammatory and antioxidant *** melatonin receptor 1B gene(MTNR1B)is expressed in,among other tissues,the brain and pancreatic beta cells,and risk variants for T2D have been reported as impairing early insulin secretion and increasing fasting glucose levels.^(1) Variants in the MTNR1B gene also have been reported in patients with depression(MDD).

关键词： MTNR1B metabolism properties.

Real-Time Fraud Detection Using Machine Learning

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Journal of Data Analysis and Information Processing 2024年第2期12卷 189-209页

作者： benjamin Borketey Department of Economics The University of Akron Akron Ohio USA

Credit card fraud remains a significant challenge, with financial losses and consumer protection at stake. This study addresses the need for practical, real-time fraud detection methodologies. Using a Kaggle credit card dataset, I tackle class imbalance using the Synthetic Minority Oversampling Technique (SMOTE) to enhance modeling efficiency. I compare several machine learning algorithms, including Logistic Regression, Linear Discriminant Analysis, K-nearest Neighbors, Classification and Regression Tree, Naive Bayes, Support Vector, Random Forest, XGBoost, and Light Gradient-Boosting Machine to classify transactions as fraud or genuine. Rigorous evaluation metrics, such as AUC, PRAUC, F1, KS, Recall, and Precision, identify the Random Forest as the best performer in detecting fraudulent activities. The Random Forest model successfully identifies approximately 92% of transactions scoring 90 and above as fraudulent, equating to a detection rate of over 70% for all fraudulent transactions in the test dataset. Moreover, the model captures more than half of the fraud in each bin of the test dataset. SHAP values provide model explainability, with the SHAP summary plot highlighting the global importance of individual features, such as “V12” and “V14”. SHAP force plots offer local interpretability, revealing the impact of specific features on individual predictions. This study demonstrates the potential of machine learning, particularly the Random Forest model, for real-time credit card fraud detection, offering a promising approach to mitigate financial losses and protect consumers.

关键词： Credit Card Fraud Detection Machine Learning SHAP Values Random Forest

SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

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Cellular & Molecular Immunology 2024年第2期21卷 171-183页

作者： benjamin L.Sievers Mark T.K.Cheng Kata Csiba Bo Meng Ravindra K.Gupta Department of Medicine University of CambridgeCambridgeUK Cambridge Institute of Therapeutic Immunology&Infectious Disease(CITID) Department of MedicineUniversity of CambridgeCambridgeUk

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of *** about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged *** humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less ***,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense *** also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

关键词： SARS-CoV-2 Innate immune response Interferon Cytokines Inflammation Antiviral targets