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Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia

Cell stem cell 2025年

作者： Maria Sirenko Soobeom Lee Zhengxi Sun Ronan Chaligne Sanam Loghavi Georgios Asimomitis Charlotte K Brierley Elsa Bernard Sheng F Cai Robert M Myers Bettina Nadorp Junya Sango Morgan Lallo Max F Levine Dylan Domenico Juan E Arango Ossa Juan S Medina-Martinez Kamal Menghrajani Audrey Lasry Alice S Mims Helee Desai Andrea Laganson Chris Famulare Minal Patel Gerard Lozanski Kelly L Bolton Aaron D Viny Mikhail Roshal Ross L Levine Eirini P Papapetrou Eytan M Stein Dan A Landau Ann-Kathrin Eisfeld Iannis Aifantis Elli Papaemmanuil Department of Pathology New York University Grossman School of Medicine New York NY USA Laura and Isaac Perlmutter Cancer Center New York University Grossman School of Medicine New York NY USA Louis V. Gerstner Jr. Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer Center New York NY USA Computational Oncology Service Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA. Department of Biology New York University New York NY USA. Laura and Isaac Perlmutter Cancer Center New York University Grossman School of Medicine New York NY USA. Program for Computational and Systems Biology Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA. Computational Oncology Service Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Biomedical Systems Laboratory Department of Mechanical Engineering National Technical University of Athens Athens Greece. Medical Research Council Weatherall Institute of Molecular Medicine University of Oxford Oxford UK NIHR Biomedical Research Centre University of Oxford Oxford UK. Leukemia Service Department of Medicine Center for Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York NY USA. Tri-Institutional MD-PhD Program Weill Cornell Medicine Rockefeller University Memorial Sloan Kettering Cancer Center New York NY USA. Division of Precision Medicine Department of Medicine New York University School of Medicine New York NY USA. Department of Oncological Sciences Tisch Cancer Institute Center for Advancement of Blood Cancer Therapies Icahn School of Medicine at Mount Sinai New York NY USA. Vilcek Institute of Graduate Biomedical Sciences NYU Grossman School of Medicine N

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.

关键词： IDH inhibitors IDH1/2 mutations acute myeloid leukemia cellular hierarchy clonal architecture clonal evolution relapse single-cell transcriptomics targeted therapy treatment resistance

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Evaluation of Interoperability between Automation systems using Multi-criteria Methods

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Procedia Manufacturing 2017年 11卷 1837-1845页

作者： Saturno, Maicon Ramos, Luiz Felipe Pierin Polato, Fabrício Deschamps, Fernando de Freitas Rocha Loures, Eduardo Graduate Program in Industrial and Systems Engineering (PPGEPS) Polytechnic School Pontifical Catholic University of Parana (PUCPR) Rua Imaculada Conceição Curitiba 1155 Paraná Brazil Dominus – Automação Sistemas e Acionamentos Avenida Manoel Ribas 8.120 Curitiba Paraná Brazil Department of Mechanical Engineering (DEMEC) Federal University of Paraná (UFPR) Rua Coronel Francisco Heráclito dos Santos Curitiba 230 Paraná Brazil Department of Electro-tecnology (DAEL) Federal University of Technology – Paraná (UTFPR) Avenida Sete de Setembro Curitiba 3033 Paraná Brazil

The diagnosis of automation systems in an existing production system through the analysis of the interoperability level between its components represents the first step in its evaluation for improving it towards alignment with Industry 4.0. The analysis of the level of interoperability finds in the multi-criteria decision making methods an auxiliary tool to evaluate and classify the solution. This work uses the AHP method for this evaluation, drawing criteria from the literature and expert experience. The application of the method is illustrated, showing that it can direct investment decisions. © 2017 The Authors

关键词： automation systems Automation technology (AT) diagnosis interoperability multi-criteria methods

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Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

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Nature medicine 2024年第12期30卷 3779页

作者： Sebastian Moguilner Sandra Baez Hernan Hernandez Joaquín Migeot Agustina Legaz Raul Gonzalez-Gomez Francesca R Farina Pavel Prado Jhosmary Cuadros Enzo Tagliazucchi Florencia Altschuler Marcelo Adrián Maito María E Godoy Josephine Cruzat Pedro A Valdes-Sosa Francisco Lopera John Fredy Ochoa-Gómez Alfredis Gonzalez Hernandez Jasmin Bonilla-Santos Rodrigo A Gonzalez-Montealegre Renato Anghinah Luís E d'Almeida Manfrinati Sol Fittipaldi Vicente Medel Daniela Olivares Görsev G Yener Javier Escudero Claudio Babiloni Robert Whelan Bahar Güntekin Harun Yırıkoğulları Hernando Santamaria-Garcia Alberto Fernández Lucas David Huepe Gaetano Di Caterina Marcio Soto-Añari Agustina Birba Agustin Sainz-Ballesteros Carlos Coronel-Oliveros Amanuel Yigezu Eduar Herrera Daniel Abasolo Kerry Kilborn Nicolás Rubido Ruaridh A Clark Ruben Herzog Deniz Yerlikaya Kun Hu Mario A Parra Pablo Reyes Adolfo M García Diana L Matallana José Alberto Avila-Funes Andrea Slachevsky María I Behrens Nilton Custodio Juan F Cardona Pablo Barttfeld Ignacio L Brusco Martín A Bruno Ana L Sosa Ortiz Stefanie D Pina-Escudero Leonel T Takada Elisa Resende Katherine L Possin Maira Okada de Oliveira Alejandro Lopez-Valdes Brian Lawlor Ian H Robertson Kenneth S Kosik Claudia Duran-Aniotz Victor Valcour Jennifer S Yokoyama Bruce Miller Agustin Ibanez Latin American Brain Health Institute Universidad Adolfo Ibañez Santiago de Chile Chile. Cognitive Neuroscience Center Universidad de San Andrés Buenos Aires Argentina. Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston MA USA. Universidad de los Andes Bogota Colombia. Global Brain Health Institute (GBHI) University of California San Francisco CA USA. Global Brain Health Institute (GBHI) Trinity College Dublin Dublin Ireland. The University of California Santa Barbara (UCSB) Santa Barbara CA USA. Escuela de Fonoaudiología Universidad San Sebastián Santiago de Chile Chile. Grupo de Bioingeniería Decanato de Investigación Universidad Nacional Experimental del Táchira San Cristóbal Venezuela. Advanced Center for Electrical and Electronic Engineering Universidad Técnica Federico Santa María Valparaíso Chile. University of Buenos Aires Buenos Aires Argentina. The Clinical Hospital of Chengdu Brain Sciences Institute University of Electronic Sciences and Technology of China Chengdu China. Technology of China Chengdu China. Cuban Neuroscience Center La Habana Cuba. Grupo de Neurociencias de Antioquia (GNA) University of Antioquia Medellín Colombia. Department of Psychology Master Program of Clinical Neuropsychology Universidad Surcolombiana Neiva Neiva Colombia. Department of Psychology Universidad Cooperativa de Colombia Arauca Colombia. Neurocognition and Psychophysiology Laboratory Universidad Surcolombiana Neiva Colombia. Reference Center of Behavioural Disturbances and Dementia School of Medicine University of Sao Paulo Sao Paulo Brazil. Traumatic Brain Injury Cognitive Rehabilitation Out-Patient Center University of Sao Paulo Sao Paulo Brazil. Center for Social and Cognitive Neuroscience School of Psychology Universidad Adolfo Ibáñez Santiago Chile. Neuropsychology and Clinical Neuroscience Laboratory (LANNEC) Physiopathology Program-Institute of Biomedical Sciences (ICBM) Neuroscience and East Neuroscience Dep

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Guest editorial: The 2016 capstone design conference

Guest editorial: The 2016 capstone design conference

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作者： Brackin, Patsy Howe, Susannah Rogers, Peter Stanfill, R. Keith Beyerlein, Steven Kanai, Junichi Vallino, Jim Palo, Scott Department of Mechanical Engineering Rose-Hulman Institute of Technology 5500 Wabash Avenue CM 165 Terre HauteIN47803 United States Picker Engineering Program Smith College 151 Ford Hall NorthamptonMA01063 United States Department of Engineering Education Ohio State University 3070 Smith Laboratory 174 W. 18th Avenue ColumbusOH43210 United States Engineering Innovation Institute University of Florida P.O. Box 116000 GainesvilleFL32611-6000 United States Department of Mechanical Engineering University of Idaho 875 Perimeter Drive MoscowID83844-0902 United States Department of Electrical Computer and Systems Engineering Rensselaer Polytechnic Institute TroyNY United States Department of Software Engineering Rochester Institute of Technology 134 Lomb Memorial Drive RochesterNY14623-5608 United States Department of Aerospace Engineering Sciences University of Colorado 429 UCB BoulderCO80309 United States

The goal of the 2016 Capstone Design Conference held in Columbus, OH was to build upon the success of previous conferences (2007 and 2010 in Boulder, CO, 2012 in Champaign, IL, and 2014 in Columbus, OH) and expand the community of educators, students, and industry members engaged in discussing, analyzing, and improving capstone design education. Sessions at the 2016 Capstone Design Conference were designed for vibrant sharing of ideas and experiences across the capstone community via interactive panel sessions, poster session socials, hands-on workshops, and other formal and informal networking activities. This editorial discusses conference planning, structure, and feedback. Technical papers that follow in this issue document scholarship surrounding noteworthy capstone course innovations. Most of these began as four page peer-reviewed papers included in the conference proceedings. © 2017 TEMPUS Publications.

关键词： Teaching

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Compact localized states and flat-band generators in one dimension

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Physical Review B 2017年第11期95卷 115135-115135页

作者： Wulayimu Maimaiti Alexei Andreanov Hee Chul Park Oleg Gendelman Sergej Flach Center for Theoretical Physics of Complex Systems Institute for Basic Science (IBS) Daejeon 34051 Republic of Korea Basic Science Program Korea University of Science and Technology (UST) Daejeon 34113 Republic of Korea Faculty of Mechanical Engineering Technion Haifa 3200003 Israel New Zealand Institute for Advanced Study Center for Theoretical Chemistry & Physics Massey University Auckland 0745 New Zealand

Flat bands (FB) are strictly dispersionless bands in the Bloch spectrum of a periodic lattice Hamiltonian, recently observed in a variety of photonic and dissipative condensate networks. FB Hamiltonians are fine-tuned networks, still lacking a comprehensive generating principle. We introduce a FB generator based on local network properties. We classify FB networks through the properties of compact localized states (CLS) which are exact FB eigenstates and occupy U unit cells. We obtain the complete two-parameter FB family of two-band d=1 networks with nearest unit cell interaction and U=2. We discover a novel high symmetry sawtooth chain with identical hoppings in a transverse dc field, easily accessible in experiments. Our results pave the way towards a complete description of FBs in networks with more bands and in higher dimensions.

关键词： Electronic structure 1-dimensional systems Electron-correlation calculations Lattice models in condensed matter

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Heuristic regression method for descriptive data analysis 16

Heuristic regression method for descriptive data analysis

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16th International Conference on Environment and Electrical engineering, EEEIC 2016

作者： Gomes, Flavio A. Gomes, Viviane M. Assis, Alfredo De O. Reis, Marcio R. Da C. Da Cruz, Gelson Calixto, Wesley P. Electrical Mechanical and Computer Engineering School University of Goias Brazil Experimental and Technological Research and Study Group Federal Institute of Goias Brazil Program in Electronic Systems and Automation University of Brasilia Brazil

ISBN: (纸本)9781509023196

The purpose of this paper is to use the hybridized optimization method in order to find mathematical structures for analysis of experimental data. The heuristic optimization method will be hybridized with deterministic optimization method in order to that structures found require not knowledge about data generated experimentally. Three case studies are proposed and discussed to validate the results. The proposed method has viable solution for the analysis of experimental data and extrapolation, with mathematical expression reduced. © 2016 IEEE.

关键词： Heuristic methods

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An efficient method to estimate sorption isotherm curve coefficients

arXiv

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arXiv 2017年

作者： Berger, Julien. Busser, Thomas Dutykh, Denys Key, Nathan Mendes LOCIE 5271 CNRS Université Savoie Mont Blanc Le Bourget-du-Lac CedexF-73376 Grenoble Alpes Univ. Savoie Mont Blanc CNRS LAMA Chambéry73000 Thermal Systems Laboratory Mechanical Engineering Graduate Program Pontifical Catholic University of Paraná Rua Imaculada Conceicaõ Curitiba-Paraná1155

This paper deals with an inverse problem applied to the field of building physics to experimentally estimate three sorption isotherm coefficients of a wood fiber material. First, the mathematical model, based on convective transport of moisture, the Optimal Experiment Design (OED) and the experimental set-up are presented. Then measurements of relative humidity within the material are carried out, after searching the OED, which is based on the computation of the sensitivity functions and a priori values of the unknown parameters employed in the mathematical model. The OED enables to plan the experimental conditions in terms of sensor positioning and boundary conditions out of 20 possible designs, ensuring the best accuracy for the identification method and, thus, for the estimated parameter. Two experimental procedures were identified: I) single step of relative humidity from 10% to 75% and ii) multiple steps of relative humidity 10-75-33-75% with an 8-day duration period for each step. For both experiment designs, it has been shown that the sensor has to be placed near the impermeable boundary. After the measurements, the parameter estimation problem is solved using an interior point algorithm to minimize the cost function. Several tests are performed for the definition of the cost function, by using the L2or L∞norm and considering the experiments separately or at the same time. It has been found out that the residual between the experimental data and the numerical model is minimized when considering the discrete Euclidean norm and both experiments separately. It means that two parameters are estimated using one experiment while the third parameter is determined with the other experiment. Two cost functions are defined and minimized for this approach. Moreover, the algorithm requires less than 100 computations of the direct model to obtain the solution. In addition, the OED sensitivity functions enable to capture an approximation of the probability distribution fun

关键词： Sorption

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Soil resistivity study and simulation with finite elements method 16

Soil resistivity study and simulation with finite elements m...

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16th International Conference on Environment and Electrical engineering, EEEIC 2016

作者： Pereira, Thiago Martins De Lima, Rodrigo Alves Gomes, Viviane Margarida Gutembergue, Sostenes Alves, Aylton Jose Calixto, Wesley Pacheco Electrical Mechanical and Computer Engineering School EMC Federal University of Goias UFG Brazil Experimental and Technological Research and Study Group NExT Federal Institute of Goias IFG Brazil Program in Electronic Systems and Automation PGEA University of Brasilia UnB Brazil

ISBN: (纸本)9781509023196

This work purpose is to study the influence of concrete buried structures in grounding systems. Comparison of soil characteristics between dry and rainy seasons and soil electrical behavior was carried out. Simulations in finite element method was performed for tree layer stratified soil and the electrostatic equipotential surfaces were mapped into the region of interest. © 2016 IEEE.

关键词： Finite element method

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Author Correction: Quantitative Characterization of Structural and mechanical Properties of Boron Nitride Nanotubes in High Temperature Environments

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Scientific reports 2018年第1期8卷 4769页

作者： Xiaoming Chen Christopher M Dmuchowski Cheol Park Catharine C Fay Changhong Ke Micro- and Nanotechnology Research Center State Key Laboratory for Manufacturing Systems Engineering Xi'an Jiaotong University Xi'an Shaanxi 710049 China. Department of Mechanical Engineering State University of New York at Binghamton Binghamton New York 13902 USA. Materials Science and Engineering Program State University of New York at Binghamton Binghamton New York 13902 USA. Advanced Materials and Processing Branch NASA Langley Research Center Hampton Virginia 23681 USA. Department of Mechanical Engineering State University of New York at Binghamton Binghamton New York 13902 USA. cke@binghamton.edu. Materials Science and Engineering Program State University of New York at Binghamton Binghamton New York 13902 USA. cke@binghamton.edu.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

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Nonlinear model predictive control hardware implementation with custom-precision floating point operations

Nonlinear model predictive control hardware implementation w...

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Mediterranean Conference on Control and Automation (MED)

作者： Helon Ayala Renato Sampaio Daniel M. Muñoz Carlos Llanos Leandro Coelho Ricardo Jacobi Industrial and Systems Graduate Program Pontifical Catholic University of Parana Brazil Department of Mechanical Engineering University of Brasilia Brazil

Model predictive control (MPC) based techniques have found many applications both in academia and in industry. Its reach, however, may not be compared to classical control techniques due to e.g. the difficulty of solving an optimization problem at each sampling interval with real-time requirements. Most of the efforts to make the application of MPC viable address this problem with more efficient solvers. This paper, in contrast, proposes a new approach for a real-time MPC solution by mapping an approximate off-line solution into an artificial neural network in a FPGA (Field programmable Gate Array). We implemented a radial basis function artificial neural network on a low cost FPGA using custom precision floating point operations and tested the control on a single-link robotic manipulator. The amount of time used to calculate the control action at each time instant is in around one microsecond. The comparison between the offline and the approximate solution shows the soundness of the idea. We provide an analysis of hardware usage and execution time in order to achieve the best compromise considering the precision for a given application.

关键词： Hardware Field programmable gate arrays Optimization Real-time systems Neurons Predictive control Neural networks

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