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An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβblockade therapy

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3594-3601页

作者： Robert Pomponio Qi Tang Anthony Mei Anne Caron Bema Coulibaly Joachim Theilhaber maximilian rogers-grazado Michele Sanicola-Nadel Souad Naimi Reza Olfati-Saber Cecile Combeau Jack Pollard Tun Tun Lin Rui Wang Sanofi Translational Medicine Early Development Cambridge MA 02142USA Sanofi Artificial Intelligence and Deep Analytics Data and Data Sciences CambridgeMA 02142USA Sanofi Translational Science Vitry sur Seine 94403France Sanofi Precision Oncology Cambridge MA 02142USA Sanofi Oncology Early Development Cambridge MA 02142USA

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes(TILs)is associate with response to *** studies have identified TGFβactivity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 *** we coupled the artificial intelligence(AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβpathway *** of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution *** digital image analysis approach achieves 74%concordance with the pathologist assessment for tumor-immune *** transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβpathway activation,together with elevated TGFβsignaling activity observed in excluded and desert tumor *** present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes:immune desert,immune excluded or immune *** association between“cold”tumor-immune phenotypes and TGFβsignature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβblockade.

关键词： Digital pathology Artificial intelligence TGFβ Predictive biomarker Tumor topography T cell infiltration Transcriptomic profiling Machine learning

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Investigating the inflow into a granular bed using a locally resolved method

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Particuology 2024年第2期85卷 89-101页

作者： maximilian Brommer Maik Scharnowski Enric Illana Mahiques Siegmar Wirtz Viktor Scherer Ruhr University Bochum Institute of Energy Plant TechnologyUniversitätsstraβe 15044780BochumGermany

Discrete Element Method-Computational Fluid Dynamics(DEM/CFD)simulations of industrial-scale granular systems employ spatial averaging(porous media approach)for the fluid-particle interaction in the whole domain,which can lead to poor accuracy,for instance at flow inlets,as local particle bulk morphology is not *** paper presents an approach where the interstitial flow in crucial areas with large gradients can be resolved locally in an otherwise unresolved domain,so that a mixed resolved-unresolved method is *** a generic example to show the feasibility and performance of the new approach,the inflow of ambient air into a flat-bottom hopper through a narrow orifice is *** an experimental setup,the vertical profile of the pressure decay through the inlet and across the packing is chosen for com-parison with respective *** obtained with the conventional porous media method and the locally resolved approach are compared to these experiments for varying volume flow rates and for two different particle *** of different size as well as dodecahedrons are *** is found that although averaging methods already provide good approximations,the locally resolved method can improve the result especially when conventional drag laws are not applicable due to wall effects or if large velocity gradients exist.

关键词： DEM/CFD Packed bed Pressure drop

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Shape-changing particles for locally resolved particle geometry in DEM simulations

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Particuology 2024年第6期89卷 185-190页

作者： Enric Illana Klidi Qyteti Maik Scharnowski maximilian Brömmer Siegmar Wirtz Viktor Scherer Institute of Energy Plant Technology Ruhr-University BochumBochumGermany

Taking into account the complex shape of particles in discrete element method (DEM) simulations of large-scale granular systems is computationally demanding due to the time-consuming contact detection algorithms for polyhedral particles. In this short communication, a novel approach that locally resolves the particle shapes where needed and uses a simplified representation elsewhere, to accelerate simulations without compromising accuracy, is presented. For this purpose, a method employing a smooth transition of the particle shape representation from analytical spheres to shape-resolving polyhedra is introduced in DEM. The feasibility and correct implementation of this approach are demonstrated through simulations of hopper discharge involving spherical and dodecahedral particles from a flat bottom silo or shaft kiln. The model capabilities, in terms of accuracy as well as reduction in computational effort, are quantified for a moving bed with continuous outflow.

关键词： Polyhedron Size change Shape change Locally resolved DEM

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Ab initio density response and local field factor of warm dense hydrogen

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Matter and Radiation at Extremes 2024年第5期9卷 48-67页

作者： Tobias Dornheim Sebastian Schwalbe Panagiotis Tolias maximilian P.Böhme Zhandos A.Moldabekov Jan Vorberger Center for Advanced Systems Understanding(CASUS) D-02826 GörlitzGermany Helmholtz-Zentrum Dresden-Rossendorf(HZDR) D-01328 DresdenGermany Space and Plasma Physics Royal Institute of Technology(KTH)Stockholm SE-10044Sweden Technische Universität Dresden D-01062 DresdenGermany

We present quasi-exact ab initio path integral Monte Carlo(PIMC)results for the partial static density responses and local field factors of hydrogen in the warm dense matter regime,from solid density conditions to the strongly compressed *** full dynamic treatment of electrons and protons on the same footing allows us to rigorously quantify both electronic and ionic exchange–correlation effects in the system,and to compare the results with those of earlier incomplete models such as the archetypal uniform electron gas or electrons in a fixed ion snapshot potential that do not take into account the interplay between the two *** full electronic density response is highly sensitive to electronic localization around the ions,and our results constitute unambiguous predictions for upcoming X-ray Thomson scattering experiments with hydrogen jets and fusion *** PIMC results are made freely available and can be used directly for a gamut of applications,including inertial confinement fusion calculations and the modeling of dense astrophysical ***,they constitute invaluable benchmark data for approximate but computationally less demanding approaches such as density functional theory or PIMC within the fixed-node approximation.

关键词： local incomplete rigorous

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Comparing two IBM implementations for the simulation of uniform packed beds

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Particuology 2024年第3期86卷 1-12页

作者： Christian Gorges maximilian Brommer Christin Velten Siegmar Wirtz Enric Illana Mahiques Viktor Scherer Katharina Zahringer Berend van Wachem Mechanical Process Engineering Otto-von-Guericke-Universitat MagdeburgUniversitatsplatz 239106MagdeburgGermany Department of Energy Plant Technology Ruhr-Universitat BochumUniversitatsstraBe 15044780BochumGermany Laboratory of Fluid Dynamics and Technical Flows Otto-von-Guericke-Universitat MagdeburgUniversitatsplatz 239106MagdeburgGermany

Nowadays,the design of fixed packed bed reactors still relies on empirical correlations,which,especially for small tube to particle diameter ratios,are mostly too inaccurate because of the presence of wall ***,the simulation of fixed packed bed reactors plays an important role to predict and control the flow and process parameters in such,nowadays and in the *** of its straightforward applicability to non-uniform packings with particles of arbitrary shapes,the immersed boundary method(IBM)has advantages over other numerical methods and is used more and more *** paper compares two approaches of IBMs for the simulation of fixed bed reactors with spherical shaped *** classic,smooth approach is compared to the straightforward to implement blocked-off method for velocity fields above the fixed bed for particle Reynolds numbers of 300 and *** from experimental inline PIV-measurements of the reactor to be simulated serve as a basis for *** good agreement with the experiment is found for both simulation methodologies with higher resolutions,considering the more stable flow at a particle Reynolds number of *** in the different IBM approaches occurred for the more unsteady flow at a particle Reynolds number of *** to the blocked-off method,the smooth IBM reflects the formation of additional jets and recirculation zones better right above the bed,though increasing the fluid mesh resolution improves the accuracy of the blocked-off ***,a more diffusive behaviour is found for the blocked-off simulations due to the stairstep representation,which is avoided by using interpolation stencils as in the smooth *** higher mesh refinement in the blocked-off IBM this effect can be reduced,but this also increases the computational effort.

关键词： Immersed boundary method Packed bed reactor Uniform particle packing

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Distributed Secondary Control Based on Dynamic Diffusion Algorithm for Current Sharing and Average Voltage Regulation in DC Microgrids

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 597-607页

作者： Dawei Liao Fei Gao Daniel J.rogers Wentao Huang Dong Liu Houjun Tang Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghaiChina Department of Engineering Science University of OxfordOxford OX12JDU.K. IEEE

This paper introduces a distributed secondary control scheme for achieving current sharing and average voltage regulation objectives in a DC *** proposed scheme employs a dynamic diffusion algorithm(DDA)instead of the consensus algorithm to enable distributed communication among *** help understand DDA,the relation of DDA and other diffusion algorithms is discussed in detail and its superiority is shown by comparison with diffusion and consensus ***,considering the discrete nature and different sampling time of the digital controller and communication network,a z-domain model of the entire DC microgrid is *** influence of communication and secondary control parameters on the system stability is *** on the established model,the tolerable communication rates are ***-time simulations conducted on the OPAL-RT platform validate the effectiveness of the proposed scheme,showcasing its advantages in terms of convergence speed and stability.

关键词： Cooperative control DC microgrid diffusion algorithm discrete-time modeling distributed secondary control

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Effect of reaction and post-treatment conditions on physico-chemical properties of magnetic iron oxide nano-particles Author links open overlay panel

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Particuology 2024年第8期91卷 155-167页

作者： Masome Moeni Mohamed Edokali Matthew rogers Oscar Cespedes Louey Tliba Tamseela Habib Robert Menzel Ali Hassanpour School of Chemical and Process Engineering Faculty of Engineering and Physical ScienceUniversity of LeedsLeedsLS29JTUK School of Physics and Astronomy Faculty of Engineering and Physical ScienceUniversity of LeedsLeedsLS29JTUK Mechanical Engineering Department University of Engineering&TechnologyLahorePakistan School of Chemistry Faculty of Engineering and Physical ScienceUniversity of LeedsLeedsLS29JTUK

Poor stability and dispersibility,as well as aggregation are considered as major challenges in clinical application of iron oxide nanoparticles(IONPs).Several studies have shown that the synthesis parameters and post-synthesis treatments e.g.,drying methods,have the capability to improve the particles'***,we investigate the combined effect of synthesis and post-treatment parameters on the particle size,stability and magnetism of ***(Fe_(3)O_(4))NPs were prepared via co-precipitation and post-treated using different methods,i.e.(i)freeze dried at-53℃,0.133 mbar for 48 h(liquid nitrogen frozen(LFD)and freezer frozen(FFD)),(ii)vacuum oven dried(VOD)at 60℃for 24 h,and(iii)kept wet colloidal(WET),dispersed in deionized *** Fe_(3)O_(4)NPs’chemical functional groups,size,shape,crystallinity,stability,aggregation,porosity,and magnetic properties were further analysed using different characterisation *** results showed that,while the WET sample had the best stability and significantly less aggregation at different temperatures,amongst post-treated Fe_(3)O_(4)NPs,LFD sample exhibited the best stability(up to 37℃),dispersion and smallest polydispersity ***,all dried NPs had superparamagnetic characteristics,while,LFD Fe_(3)O_(4)NPs had better magnetic properties and stability than other drying methods.

关键词： Iron oxide nanoparticles Co-precipitation Stability Aggregation Magnetic properties

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Determinant variables on the isotopic values of particulate organic matter in a neotropical floodplain

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Journal of Oceanology and Limnology 2024年第4期42卷 1173-1185页

作者： Vinícius de ANDRADE URBANO Matheus maximilian RATZ SCOARIZE Gustavo HENRIQUE ZAIA ALVES Driele DELANIRA-SANTOS Marcela da SILVA CAETANO Evanilde BENEDITO Departamento de Biologia(DBI) Laboratório de Ecologia EnergéticaUniversidade Estadual de Maringá(UEM)Maringá87020-900Brasil Programa de Pós-graduação em Ecologia de Ambientes Aquáticos Continentais(PEA) Universidade Estadual de Maringá(UEM)Maringá87020-900Brasil Departamento de Biologia Geral Universidade Estadual de Ponta Grossa(UEPG)Campus UvaranasPonta Grossa 84030-900Brasil Australian Rivers Institute(ARI) Griffith UniversityNathan QLD 4111Australia

Particulate organic matter(POM)is an important energy source for aquatic consumers,understanding its origin and composition is essential for understanding the energetic dynamics of aquatic *** aim of this study was to analyze the relationship between POM and phytoplankton(isotopic values and chlorophyll concentration)and abiotic variables during dry and rainy *** was conducted in rivers and lagoons in the floodplain of the Upper Paraná*** found a greater difference in ^(δ13)C values of POM between sampling points than between seasons,indicating that the composition of regional sources influences the composition of POM more than dry and rainy *** addition,the concentration of chlorophyll during the dry season was positively correlated with ^(δ13)C values during that rainy ***,we found a relationship between factors limiting the growth of phytoplankton and ^(δ13)C values of POM,such as phosphate ions,indicating that variables that regulate phytoplankton growth tend to influence the composition of POM in river ***,maintaining the variables that regulate the phytoplankton community is of fundamental importance for the composition of POM,an important energy source in aquatic environments.

关键词： freshwater wetland stable isotopes food web subtropical environment

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Beyond total mesorectal excision: The emerging role of minimally invasive surgery for locally advanced rectal cancer

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2382-2385页

作者： Davina Perini Francesca Cammelli maximilian Scheiterle Jacopo Martellucci Annamaria Di Bella Carlo Bergamini Paolo Prosperi Alessio Giordano Department of Emergency and Acceptance Emergency Surgery UnitCareggi University HospitalFirenze 50137Italy

Multivisceral resection and/or pelvic exenteration represents the only potential curative treatment for locally advanced rectal cancer(LARC);however,it poses significant technical challenges,which account for the high risk of morbidity and mortality associated with the *** complete histopathologic resection is the most important determinant of patient outcomes,LARC often requires an extended resection beyond the total mesorectal excision plane to obtain clear re-section *** an era when laparoscopic surgery and robot-assisted surgery are becoming commonplace,the optimal approach to extensive pelvic inter-ventions remains ***,acceptance of the suitability of mini-mally invasive surgery is slowly gaining ***,there is still a lack of evidence in the literature about minimally invasive approaches in multiple and extensive surgical resections,highlighting the need for research studies to explore,validate,and develop this *** editorial aims to provide a critical overview of the currently available applications and challenges of minimally invasive abdo-minopelvic surgery for ***,we discuss recent developments in the field of robotic surgery for LARC,with a specific focus on new innovations and emerging frontiers.

关键词： Robotic surgery Pelvic exenteration Multivisceral resection Rectal cancer Total mesorectal excision

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Improved Mechanism for Detecting Examinations Impersonations in Public Higher Learning Institutions: Case of the Mwalimu Nyerere Memorial Academy (MNMA)

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Journal of Computer and Communications 2024年第9期12卷 160-187页

作者： Jasson Lwangisa Domition rogers Philip Bhalalusesa Selemani Ismail Department of Leadership and Management Sciences The Mwalimu Nyerere Memorial Academy Pemba Tanzania Department of Mathematics Information and Communication Technology The Open University of Tanzania Dar es Salaam Tanzania

Currently, most public higher learning institutions in Tanzania rely on traditional in-class examinations, requiring students to register and present identification documents for examinations eligibility verification. This system, however, is prone to impersonations due to security vulnerabilities in current students’ verification system. These vulnerabilities include weak authentication, lack of encryption, and inadequate anti-counterfeiting measures. Additionally, advanced printing technologies and online marketplaces which claim to produce convincing fake identification documents make it easy to create convincing fake identity documents. The Improved Mechanism for Detecting Impersonations (IMDIs) system detects impersonations in in-class exams by integrating QR codes and dynamic question generation based on student profiles. It consists of a mobile verification app, built with Flutter and communicating via RESTful APIs, and a web system, developed with Laravel using HTML, CSS, and JavaScript. The two components communicate through APIs, with MySQL managing the database. The mobile app and web server interact to ensure efficient verification and security during examinations. The implemented IMDIs system was validated by a mobile application which is integrated with a QR codes scanner for capturing codes embedded in student Identity Cards and linking them to a dynamic question generation model. The QG model uses natural language processing (NLP) algorithm and Question Generation (QG) techniques to create dynamic profile questions. Results show that the IMDIs system could generate four challenging profile-based questions within two seconds, allowing the verification of 200 students in 33 minutes by one operator. The IMDIs system also tracks exam-eligible students, aiding in exam attendance and integrates with a Short Message Service (SMS) to report impersonation incidents to a dedicated security officer in real-time. The IMDIs system was tested and found to be 98% s

关键词： Natural Language Processing (NLP) Model Impersonations Detection Dynamic Challenging Questions Traditional-in-Class Examination and Impersonation Detection

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