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Identification of Global dNA Methylation Signatures in Glioblastoma-derived Cancer Stem Cells

Journal of Genetics and Genomics 2015年第7期42卷 355-371页

作者： Eun-Joon Lee Prakash Rath Jimei Liu dungsung Ryu Lirong Pei Satish K.Noonepalle Austin Y.Shull Qi Feng N.Scott Litofsky douglas C.Miller douglas C.Anthony mark d.kirk John Laterra Libin deng Hong-Bo Xin Xinguo Wang Jeong-Hyeon Choi Huidong Shi GRU Cancer Center Georgia Regents University department of Biology College of Art and SciencesUniversity of Missouri Office of In Vitro diagnostics and Radiological Health Center for Devices and Radiological HealthFood and Drug Administration department of Biochemistry and Molecular Biology Georgia Regents University division of Neurological Surgery University of Missouri School of Medicine department of Pathology and Anatomical Sciences University of Missouri School of Medicine department of Pathology and Laboratory Medicine Brown University and Lifespan Academic Medical Center department of Neurology The Hugo W.Moser Research Institute at Kennedy Krieger Inc.and The Johns Hopkins University School of Medicine Institute of Translational Medicine Nanchang University david H.Murdock Research Institute department of Biostatistics and Epidemiology Georgia Regents University

Glioblastoma （GBM） is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the dNA methylation landscape in GBM- derived cancer stem ceils （GSCs）. Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls （a neural stem cell （NSC） line and normal brain tissue） identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary GBMs, and their counterpart GSC lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT, AJAP1 and PTPRN2. These unique dNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.

关键词： Glioblastoma Cancer stem cells dNA methylation SPINT2

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage mark L.dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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deep learning based classification of sheep behaviour from accelerometer data with imbalance

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Information Processing in Agriculture 2023年第3期10卷 377-390页

作者： kirk E.Turner Andrew Thompson Ian Harris mark Ferguson Ferdous Sohel discipline of Information Technology Murdoch UniversityMurdochWA 6150Australia Centre for Crop and Food Innovation Food Futures InstituteMurdoch UniversityMurdochWA 6150Australia College of Science HealthEngineering and EducationMurdoch UniversityMurdochWA 6150Australia neXtgen Agri Saint MartinsChristchurch 8022New Zealand

Classification of sheep behaviour from a sequence of tri-axial accelerometer data has the potential to enhance sheep *** behaviour is inherently imbalanced(e.g.,more ruminating than walking)resulting in underperforming classification for the minority activities which hold *** works have not addressed class imbalance and use traditional machine learning techniques,e.g.,Random Forest(RF).We investigated deep Learning(dL)models,namely,Long Short Term Memory(LSTM)and Bidirectional LSTM(BLSTM),appropriate for sequential data,from imbalanced *** data sets were collected in normal grazing conditions using jaw-mounted and earmounted *** to this study,alongside typical single classes,e.g.,walking,depending on the behaviours,data samples were labelled with compound classes,e.g.,walking_-*** number of steps a sheep performed in the observed 10 s time window was also recorded and incorporated in the *** designed several multi-class classification studies with imbalance being addressed using synthetic *** models achieved superior performance to traditional ML models,especially with augmented data(e.g.,4-Class+Steps:LSTM 88.0%,RF 82.5%).dL methods showed superior generalisability on unseen sheep(i.e.,F1-score:BLSTM 0.84,LSTM 0.83,RF 0.65).LSTM,BLSTM and RF achieved sub-millisecond average inference time,making them suitable for real-time *** results demonstrate the effectiveness of dL models for sheep behaviour classification in grazing *** results also demonstrate the dL techniques can generalise across different *** study presents a strong foundation of the development of such models for real-time animal monitoring.

关键词： Sheep behaviour classification data synthesis Class imbalance Grazing sheep

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Potential of ultrasound stimulation and sonogenetics in vision restoration:a narrative review

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Neural Regeneration Research 2025年第12期20卷 3501-3516页

作者： Jie Ji Chen Gong Gengxi Lu Junhang Zhang Baoqiang Liu Xunan Liu Junhao Lin Patrick Wang Biju B.Thomas mark S.Humayun Qifa Zhou department of Biomedical Engineering University of Southern CaliforniaLos AngelesCAUSA USC Roski Eye Institute Keck School of Medicine of University of Southern CaliforniaLos AngelesCAUSA Thomas Lord department of Computer Science University of Southern CaliforniaLos AngelesCAUSA Harvard Westlake School Studio CityCAUSA

Vision restoration presents a considerable challenge in the realm of regenerative medicine,while recent progress in ultrasound stimulation has displayed potential as a non-invasive therapeutic *** narrative review offers a comprehensive overview of current research on ultrasound-stimulated neuromodulation,emphasizing its potential as a treatment modality for various nerve *** examining of the efficacy of different types of ultrasound stimulation in modulating peripheral and optic nerves,we can delve into their underlying molecular ***,the review underscores the potential of sonogenetics in vision restoration,which involves leveraging pharmacological and genetic manipulations to inhibit or enhance the expression of related mechanosensitive channels,thereby modulating the strength of the ultrasound *** also address how methods such as viral transcription can be utilized to render specific neurons or organs highly responsive to ultrasound,leading to significantly improved therapeutic outcomes.

关键词： neuromodulation non-invasive optic nerve injury retinal degeneration sonogenetics ultrasound stimulation visual restoration

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循证设计对解决核心设计问题很有帮助

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中国医院建筑与装备 2012年第10期13卷 46-47页

作者： d.kirk Hamilton 美国医疗建筑学院美国建筑师协会美国德克萨斯A&M大学建筑系健康系统设计研究中心

目前,已有越来越多的建筑师、工程师、设计人员和设计公司使用相关的手段以提高他们决策的质量。循证设计在解决那些对项目结果有重要影响且所知甚少的核心设计问题上很有帮助。但是,并不是在进行每个决策的时候都需要依据科学研究的成... 详细信息

目前,已有越来越多的建筑师、工程师、设计人员和设计公司使用相关的手段以提高他们决策的质量。循证设计在解决那些对项目结果有重要影响且所知甚少的核心设计问题上很有帮助。但是,并不是在进行每个决策的时候都需要依据科学研究的成果。我认为,严谨的循证研究在结合工程项目的时候。

关键词：设计循证科学研究工程项目建筑师工程师

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Adventures Beyond Amdahl's Law:How Power-Performance Measurement and Modeling at Scale drive Server and Supercomputer design

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Journal of Computer Science & Technology 2023年第1期38卷 80-86页

作者： kirk W.Cameron Computer Science Virginia TechWashington D.C.VA 24061U.S.A.

Amdahl’s Law painted a bleak picture for large-scale *** implication was that parallelism was limited and therefore so was potential *** Amdahl’s contribution was seminal and important,it drove others vested in parallel processing to define more clearly why large-scale systems are critical to our future and how they fundamentally provide opportunities for speedup beyond Amdahl’s *** the early 2000s,much like Amdahl,we predicted dire consequences for large-scale systems due to power *** our early work was often dismissed,the implications were clear to some:power would ultimately limit *** this retrospective,we discuss how power-performance measurement and modeling at scale led to contributions that have driven server and supercomputer design for more than a *** the influence of these techniques is now indisputable,we discuss their connections,limits and additional research directions necessary to continue the performance gains our industry is accustomed to.

关键词： Amdahl’s Law speedup power-aware computing power modeling performance modeling performance prediction power measurement

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循证设计:用科学研究指导医院设计

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中国医院建筑与装备 2012年第10期13卷 37-41页

作者： d.kirk Hamilton 柏鑫(译) 朱雪梅(译校) 美国德克萨斯A&M大学建筑系美国建筑师协会美国医疗建筑学院

建筑师在设计过程中会根据自己在建筑及其他领域积累的知识而做出决策,其经常参照的领域包括几何学、数学、物理学及工程学等。他们运用的许多知识都建立在科学研究的基础上,如材料力学、防潮原理、土壤受力、结构原理和房地产经济学。... 详细信息

建筑师在设计过程中会根据自己在建筑及其他领域积累的知识而做出决策,其经常参照的领域包括几何学、数学、物理学及工程学等。他们运用的许多知识都建立在科学研究的基础上,如材料力学、防潮原理、土壤受力、结构原理和房地产经济学。在最新的建筑实践（包括医院设计）中。

关键词：医院设计科学研究循证建筑师材料力学结构原理几何学工程学

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Numerical modelling of high-temperature superconducting dynamos:A review

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Superconductivity 2023年第1期5卷 1-16页

作者： mark d Ainslie department of Engineering King’s College LondonStrandLondon WC2R 2LSUnited Kingdom

The high‐temperature superconducting(HTS)dynamo enables injection of large dC currents into a superconducting coil,without the need for thermally‐inefficient current *** of this important advantage,there is significant interest in using such technology to energise superconducting coils in superconducting rotating machines and NMR/MRI *** the extensive experimental work carried out over the past decade,there was–until very recently–considerable confusion and debate regarding the physical origin of the HTS dynamo’s dC output *** modelling has played a key role in elucidating the underlying physics of such devices and several different numerical models have now been developed as useful and cost‐effective tools to not only explain and further examine experimental results,but also optimise and improve dynamo *** review summarises all of the developments in this important area over recent years,including modelling the open‐circuit voltage behaviour in 2d and 3d,the definition of a new benchmark problem for the HTS modelling community,investigating key dynamo parameters,modelling dynamic coil charging behaviour and calculating losses.A view towards the future is provided,including the outstanding challenges and the developments required to address these.

关键词： HTS modelling HTS dynamo HTS flux pump High temperature superconductors Numerical simulation Finite‐element method

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A programmable microfluidic platform to monitor calcium dynamics in microglia during inflammation

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Microsystems & Nanoengineering 2024年第4期10卷 285-296页

作者： Adam Shebindu durga Kaveti Linda Umutoni Gia kirk Michael d.Burton Caroline N.Jones department of Bioengineering University of Texas at DallasRichardsonTX 75080USA department of Biomedical Engineering UT Southwestern Medical CenterDallasTX 75390USA department of Neuroscience University of Texas at DallasRichardsonTX 75080USA

Neuroinflammation is characterized by the elevation of cytokines and adenosine triphosphate(ATP),which in turn activates *** immunoregulatory molecules typically form gradients in vivo,which significantly influence microglial behaviors such as increasing calcium signaling,migration,phagocytosis,and cytokine *** microglial calcium signaling in the context of inflammation holds the potential for developing precise therapeutic strategies for neurological ***,the current calcium imaging systems are technically challenging to operate,necessitate large volumes of expensive reagents and cells,and model immunoregulatory molecules as uniform concentrations,failing to accurately replicate the in vivo *** this study,we introduce a novel calcium monitoring micro-total analysis system(CAM-μTAS)designed to quantify calcium dynamics in microglia(BV2 cells)within defined cytokine *** programmable pneumatically actuated lifting gate microvalve arrays and a Quake valve,CAM-μTAS delivers cytokine gradients to microglia,mimicking *** device automates sample handling and cell culture,enabling rapid media changes in just 1.5 s,thus streamlining the experimental *** analyzing BV2 calcium transient latency to peak,we demonstrate locationdependent microglial activation patterns based on cytokine and ATP gradients,offering insights contrasting those of non-gradient-based perfusion *** harnessing advancements in microsystem technology to quantify calcium dynamics,we can construct simplified human models of neurological disorders,unravel the intricate mechanisms of cell-cell signaling,and conduct robust evaluations of novel therapeutics.

关键词： lifting dynamics offering

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Addressing nonresponse bias in forest inventory change estimation using response homogeneity classifications

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Forest Ecosystems 2023年第1期10卷 125-131页

作者： James A.Westfall mark d.Nelson U.S.Forest Service Northern Research StationYorkPAUSA U.S.Forest Service Northern Research StationSt.PaulMNUSA

Estimating amounts of change in forest resources over time is a key function of most national forest inventories(NFI). As this information is used broadly for many management and policy purposes, it is imperative that accurate estimations are made from the survey sample. Robust sampling designs are often used to help ensure representation of the population, but often the full sample is unrealized due to hazardous conditions or possibly lack of land access permission. Potentially, bias may be imparted to the sample if the nonresponse is nonrandom with respect to forest characteristics, which becomes more difficult to assess for change estimation methods that require measurements of the same sample plots at two points in time, i.e., remeasurement. To examine potential nonresponse bias in change estimates, two synthetic populations were constructed: 1) a typical NFI population consisting of both forest and nonforest plots, and 2) a population that mimics a large catastrophic disturbance event within a forested population. Comparisons of estimates under various nonresponse scenarios were made using a standard implementation of post-stratified estimation as well as an alternative approach that groups plots having similar response probabilities(response homogeneity). When using the post-stratified estimators, the amount of change was overestimated for the NFI population and was underestimated for the disturbance population, whereas the response homogeneity approach produced nearly unbiased estimates under the assumption of equal response probability within groups. These outcomes suggest that formal strategies may be needed to obtain accurate change estimates in the presence of nonrandom nonresponse.

关键词： disturbance Post-stratification Land use conversion Sample bias

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