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Natural Killer Cells:Biology and Clinical Use in Cancer Therapy

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Cellular & Molecular Immunology 2004年第1期1卷 12-21页

作者： William H.D.Hallett William j.murphy Department of Microbiology and Immunology University of Nevada School of Medicine.University of Nevada.Reno.Reno.NV.USA.

Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,as well as the ability to elicit potent anti-tumor *** the clinical results for these processes are still *** understanding of NK cell biology,from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential of NK *** of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential *** modulation of activating and inhibitory receptors may hold the key to clinical success involving NK ***-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,and provide superior graft-versus-tumor (GVT) *** clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of *** review will attempt to be a synthesis of current knowledge concerning NK cells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologic *** & Molecular Immunology.2004;1(1):12-21.

关键词： NK cell BMT GVHD GVT

Unsupervised ore/waste classification on open-cut mine faces using close-range hyperspectral data

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Geoscience Frontiers 2023年第4期14卷 89-99页

作者： Lloyd Windrim Arman Melkumyan Richard j.murphy Anna Chlingaryan Raymond Leung Rio Tinto Centre for Mine Automation Australian Centre for Field RoboticsThe University of SydneySydney 2006Australia

The remote mapping of minerals and discrimination of ore and waste on surfaces are important tasks for geological applications such as those in *** tasks have become possible using ground-based,close-range hyperspectral sensors which can remotely measure the reflectance properties of the environ-ment with high spatial and spectral ***,autonomous mapping of mineral spectra mea-sured on an open-cut mine face remains a challenging problem due to the subtleness of differences in spectral absorption features between mineral and rock classes as well as variability in the illumination of the *** additional layer of difficulty arises when there is no annotated data available to train a supervised learning algorithm.A pipeline for unsupervised mapping of spectra on a mine face is pro-posed which draws from several recent advances in the hyperspectral machine learning *** proposed pipeline brings together unsupervised and self-supervised algorithms in a unified system to map minerals on a mine face without the need for human-annotated training *** pipeline is eval-uated with a hyperspectral image dataset of an open-cut mine face comprising mineral ore martite and non-mineralised *** combined system is shown to produce a superior map to its constituent algo-rithms,and the consistency of its mapping capability is demonstrated using data acquired at two differ-ent times of day.

关键词： Hyperspectral imaging Mineral mapping Open-cut mine face Machine learning Convolutional neural networks Illumination invariance

A near infrared spectroscopy calibration for the prediction of fresh grass quality on Irish pastures

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Information Processing in Agriculture 2022年第2期9卷 243-253页

作者： Darren j.murphy Bernadette O’Brien Michael O’Donovan Tomas Condon Michael D.murphy Teagasc Animal&Grassland Research and Innovation CentreMooreparkFermoyCo.CorkIreland Department of Process Energy and Transport EngineeringMunster Technological UniversityCorkIreland

The aim of this study was to develop near infrared spectroscopy(NIRS)calibrations to predict quality parameters,dry matter(DM,g kg1)and crude protein(CP,g kg1 DM),in fresh un-dried *** of these parameters would enable more precise allocation of quality herbage to grazing *** ryegrass samples(n=1615)were collected over the 2017 and 2018 grazing seasons at Teagasc Moorepark to develop a NIRS calibration *** samples were collected for an independent validation dataset(n=197)during the 2019 grazing *** were scanned using a FOSS 6500 spectrometer at 2 nm intervals in the range of 1100~2500 nm and absorption was recorded as log 1/Reflec*** wet chemistry analysis was carried out for both parameters and the resultant data were calibrated against spectral data by means of modified partial least squares regression.A range of mathematical spectral treatments were examined for each calibration,which were ranked in order of standard error of prediction(SEP)and ratio of percent deviation(RPD).Best performing calibrations achieved high predictive precision for DM(R2=0.86 SEP=9.46 g kg1,RPD=2.60)and moderate precision for CP(R2=0.84 SEP=20.38 g kg1 DM,RPD=2.37).These calibrations will aid the optimisation of grassland management and the development of precision agricultural technologies.

关键词： Near infrared spectroscopy Fresh grass analysis Grassland management Grass quality Precision agriculture

CO2-mediated bicarbonate conversion to concentrated formate in a CEM-based electrolyzer

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journal of Energy Chemistry 2025年第1期100卷 605-611页

作者： Haocheng Xiong Donghuan Wu Haonan Li andrew Li Qikun Hu Siyao Song Bingjun Xu Qi Lu State Key Laboratory of Chemical Engineering Department of Chemical Engineering Tsinghua University College of Chemistry and Molecular Engineering Peking University Ordos Laboratory

Renewable energy-driven bicarbonate conversion to valuable chemicals presents an attractive strategy for mitigating CO2emissions,as bicarbonate can be efficiently generated from the capture of atmospheric CO2using alkaline solutions with reactive *** this work,we present a CO2-mediated bicarbonate conversion to pure formate using a cation exchange membrane-based electrolyzer with a 25 cm2electrode *** electrolysis achieved selectivities exceeding 75%for formate at a total current of 2.5 A,achieving formate concentrations up to 1.2 M and yields as high as 95%over extended *** techno-economic assessment confirmed the economic viability of the process,highlighting the potential for bicarbonate electrolysis as a sustainable method for producing valuable chemicals.

关键词： Electrocatalysis Techno-economic assessments Electrochemistry Flow electrolyzer

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

The role of organic electron donors in the initiation of BHAS base-induced coupling reactions between haloarenes and arenes

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Science China Chemistry 2019年第11期62卷 1425-1438页

作者： andrew j.Smith Darren L.Poole john A.murphy Department of Pure and Applied Chemistry University of StrathclydeStrathclydeGlasgow G11XLUnited Kingdom Flexible Discovery Unit GlaxoSmithKline Medicines Research CentreStevenageSG12NYUnited Kingdom

Coupling reactions between haloarenes and arenes(including heteroarenes)that are conducted without added transition metals but in the presence of KOtBu or NaOtBu,have been a topic of great interest since their discovery in *** organic structures act as additives that assist these *** additives are converted into organic electron donors by the butoxide base and this leads to initiation of the coupling reactions,which proceed by radical chain *** review provides an overview of the initiation stages of these reactions.

关键词： organic electron donor potassium tert-butoxide electron transfer base-promoted homolytic aromatic substitution(BHAS) coupling benzyne

在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相关性研究(英文)

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中国实验血液学杂志 2006年第5期14卷 934-940页

作者：王昭 William j.murphy 首都医科大学附属北京友谊医院血液内科北京100050 美国国立卫生研究院分子免疫调控研究实验室

本研究评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为今后的异基因造血干细胞移植的临床应用提供科学依据。经过致死剂量照射的BALB/c小鼠接受异基因C57BL/6小鼠的骨髓移植。根据回输的细胞不同实验分为4组:B6CCR5K... 详细信息

本研究评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为今后的异基因造血干细胞移植的临床应用提供科学依据。经过致死剂量照射的BALB/c小鼠接受异基因C57BL/6小鼠的骨髓移植。根据回输的细胞不同实验分为4组:B6CCR5KO组,受者接受C57BL/6CCR5-/-小鼠骨髓和脾脏细胞;B6WT组,受者接受野生型C57BL/6小鼠骨髓和脾脏细胞;B6CCR5KOBMC组,受者只接受C57BL/6CCR5-/-小鼠骨髓细胞;B6WTBMC组,受者只接受野生型C57BL/6小鼠骨髓细胞。结果表明:较之B6WT组,B6CCR5KO组小鼠以更快的速度死于急性GVHD;其受者体内的CD8+T细胞更大量的增殖;其T细胞恢复后产生更多的INF-γ和TNF-α并且由于其T细胞有丝分裂原刀豆素水平处于较高水平,从而进一步促进T细胞的增殖,提示CCR5的作用之一是下调参与排异反应的供者CD8+T细胞的增殖。组织学评价提示,移植剔除CCR5基因受者细胞的小鼠肾脏出现了病理损伤并且肝脏存在有更为严重的病理变化。结论:剔除CCR5基因的异基因骨髓移植使GVHD发病率的增加,供者CD8+T细胞在受者体内增殖增加以及肝肾损害加重,这提示CCR5在异基因骨髓移植中起着重要作用。

关键词： CCR5 GVHD 异基因造血干细胞移植 CD8^+细胞

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NK细胞用于肿瘤免疫治疗的研究进展

中华微生物学和免疫学杂志 2001年第2期21卷 239-240页

作者：田志刚孙汭 William j.murphy 山东省医学科学院肿瘤生物治疗研究中心 SAIC-Frederick NCI-FCRDCFrederickMD21701USA

NK细胞是具有多种免疫学功能的淋巴样细胞。NK细胞的描述可以追溯到25年前，但有关NK细胞识别转化细胞和病毒感染细胞的机制至今仍令人困惑。缺乏真正意义的特有标志也是NK细胞研究的一大难题，目前多采用“阳性筛选”(NK细胞具备相对... 详细信息

NK细胞是具有多种免疫学功能的淋巴样细胞。NK细胞的描述可以追溯到25年前，但有关NK细胞识别转化细胞和病毒感染细胞的机制至今仍令人困惑。缺乏真正意义的特有标志也是NK细胞研究的一大难题，目前多采用“阳性筛选”(NK细胞具备相对特异的标志)和“阴性排除”(NK细胞绝对不具备的标志)相结合的办法来给NK细胞定性。人类NK细胞为CD56和CD16阳性，CD3、CD4和CD19为阴性。少部分NK细胞可以为CD8阳性。小鼠NK细胞为NK1.1和ASGM1阳性，CD3、CD4和CD8为阴性。NK细胞杀伤肿瘤细胞不受MHC限制，也不需预先与抗原接触或显示任何记忆反应。NK细胞对肿瘤的杀伤优势表现为直接溶解和分泌细胞因子两个方面，其杀伤肿瘤既可通过穿孔素又可通过Fas配基。NK细胞可以产生TNF-α、IFN-γ和IL-1，这些细胞因子在NK细胞抗癌反应中有十分重要地位。NK细胞具有对异体骨髓快速排异的能力，但并不介导实体组织的移植排异〔1，2〕，NK细胞对异体骨髓的排异功能可以追溯到30年前，但NK细胞对造血干/祖细胞杀伤的机制仍不清楚，可以肯定地说并不仅限于NK细胞的杀伤功能〔1〕。

关键词：肿瘤免疫疗法 NK细胞

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic