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Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1349-1365页

作者： Noel E Donlon Maria Davern Andrew sheppard Fiona O'Connell Brendan Moran timothy s nugent Aisling Heeran James J Phelan Anshul Bhardwaj Christine Butler Narayanasamy Ravi Claire L Donohoe Niamh Lynam-Lennon stephen Maher John V Reynolds Joanne Lysaght Cancer Immunology and Immunotherapy Group Department of SurgeryTrinity Translational Medicine Institute and Trinity St James’s Cancer InstituteTrinity College DublinSt James’s HospitalDublin D08Ireland

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer ***,inducing a purposeful synergistic response between conventional therapies and the immune system remains *** release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune ***,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells *** To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic *** We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of *** expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)*** Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in *** increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral *** with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low *** In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic *** also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

关键词： Damage associated molecular patterns HMGB1 Calreticulin Oesophageal adenocarcinoma T cells Radiation

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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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Tale of mitochondria and mitochondria-associated ER membrane in patient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry timothy Barrett sovan sarkar I-sTEM CECSCorbeil-EssonnesFrance UniversitéParis-saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and Genomic sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

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Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration Research 2025年第2期20卷 481-482页

作者： Khaled Alok timothy G.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA Translational Brain Research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNs),have attracted considerable attention in conditions where cortical spreading depolarizations(CsDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CsDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CsDs,particularly emphasizing TNs,and to underscore TNs’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

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Plate tectonics in relation to mantle temperatures and metamorphic properties

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science China Earth sciences 2020年第5期63卷 634-642页

作者： timothy KUsKY state Key Laboratory of Geological Processes and Mineral Resources Center for Global TectonicsSchool of Earth SciencesChina University of GeosciencesWuhan 430074China Three Gorges Research Center for Geohazards China University of GeosciencesWuhan 430074China

When plate tectonics emerged and how it has evolved over Earth history are two of the most fundamental challenges in Earth *** questions are tackled using a holistic approach to analyze tectonic styles in the history of Earth,giving rise to the interpretation of two styles of plate tectonics since the *** these interpretations,there are different styles of deformation and metamorphism between early times dominated by warm subduction,and later times preferring cold *** two styles of plate tectonics are recorded by different properties of regional metamorphism at convergent plate boundaries,which are linked to the differences in mantle temperature between the Archean and Phanerozoic.A transition to modern plate tectonics is recorded by the signature of blueschist facies metamorphism developed in the *** is consistent with geological evidence for the operation of ancient plate tectonics since the early *** temporal cooling of the mantle explains the geochemical trends of mantle-derived melts,the likely change from numerous small plates to fewer but larger plates,changes in thickness and preservation of oceanic crust and lithosphere in accretionary and collisional orogens,and led to the oxygenation of the surface environment providing the environments needed to foster life.

关键词： Plate tectonics Precambrian Accretionary orogen Mantle temperature Metamorphic facies series

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Comparison of fusion methods based on DsT and DBN in human activity recognition

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控制理论与应用（英文版） 2011年第1期9卷 18-27页

作者： Andrei TOLsTIKOV Jit BIsWAs Chris nugent Guido PARENTE Institute for Infocomm Research Networking Protocols Department1 Fusionopolis Way#21-01Singapore 138632 school of Computing and Mathematics University of UlsterShore RoadNewtownabbeyBT37 0QBU.K.

Ambient assistive living environments require sophisticated information fusion and reasoning techniques to accurately identify activities of a person under care. In this paper, we explain, compare and discuss the application of two powerful fusion methods, namely dynamic Bayesian networks (DBN) and Dempster-shafer theory (DsT), for human activity recognition. Both methods are described, the implementation of activity recognition based on these methods is explained, and model acquisition and composition are suggested. We also provide functional comparison of both methods as well as performance comparison based on the publicly available activity dataset. Our findings show that in performance and applicability, both DsT and DBN are very similar; however, significant differences exist in the ways the models are obtained. DsT being top-down and knowledge-based, differs significantly in qualitative terms, when compared with DBN, which is data-driven. These qualitative differences between DsT and DBN should therefore dictate the selection of the appropriate model to use, given a particular activity recognition application.

关键词： Dynamic Bayesian networks Dempster-shafer theory Healthcare monitoring Ambient assisted living Activity recognition

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Targeting PP2A for cancer therapeutic modulation

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Cancer Biology & Medicine 2022年第10期19卷 1428-1439页

作者： Halle Ronk Jared s.Rosenblum timothy Kung Zhengping Zhuang Neuro-Oncology Branch National Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA

Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal *** phosphatase 2A(PP2A)is highly conserved and is the predominant serine/threonine phosphatase in the nervous system,constituting more than 70%of all neuronal ***2A is involved in diverse regulatory functions,including cell cycle progression,apoptosis,and DNA *** PP2A has historically been identified as a tumor suppressor,inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various ***100,a water-soluble,small-molecule competitive inhibitor of PP2A,has shown particular promise as a chemo-and radio-sensitizing *** success has led to a profusion of clinical trials on LB100 adjuvant therapies,including a phase I trial in extensive-stage small-cell lung cancer,a phase I/II trial in myelodysplastic syndrome,a phase II trial in recurrent glioblastoma,and a completed phase I trial assessing the safety of LB100 and docetaxel in various relapsed solid ***,we review the development of LB100,the role of PP2A in cancer biology,and recent advances in targeting PP2A inhibition in immunotherapy.

关键词： Chemo-sensitization clinical trials colorectal cancer glioblastoma immunotherapy LB100 protein phosphatase 2A PP2A inhibition radio-sensitization small molecule inhibitor

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Colorectal cancer:Metastases to a single organ

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World Journal of Gastroenterology 2015年第41期21卷 11767-11776页

作者： sina Vatandoust timothy J Price Christos s Karapetis Department of Medical Oncology Flinders Medical Centre Flinders Centre for Innovation in Cancer Flinders University Department of Medical Oncology The Queen Elizabeth Hospital The University of Adelaide

Colorectal cancer(CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site(solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ.

关键词： Colorectal cancer Metastasis Prognosis Disease man

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Netrin-1 marshals mitochondrial movement,morphology,and metabolism in myelin

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Neural Regeneration Research 2021年第12期16卷 2399-2400页

作者： Diane sNakamura timothy E.Kennedy Montreal Neurological Institute Department of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada

Oligodendrocytes are the myelinating cells of the central nervous system(CNs)that ensheath nearby axons to support action potential propagation and axon *** involves the rapid production of lipid-rich membrane,compaction of the multilamellar myelin sheath,and the resultant restriction of cytoplasm to non-compact *** myelination,septate-like junctions form between the axon and lateral cytoplasmic endings of the myelin sheath at a specialized domain called the paranode(Figure 1A).

关键词： Figure resultant system

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Absolute parameters of young stars:PU Pup

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Research in Astronomy and Astrophysics 2021年第10期21卷 151-163页

作者： Ahmet Erdem Derya surgit timothy s.Banks Burcu Ozkardes Edwin Budding Canakkale Onsekiz Mart University Astrophysics Research Center and Ulupinar ObservatoryTR-17100CanakkaleTurkey Department of Physics Faculty of Arts and SciencesCanakkale Onsekiz Mart UniversityTerzioglu KampusuTR-17100CanakkaleTurkey Department of space sciences and Technologies Faculty of Arts and SciencesCanakkale Onsekiz Mart UniversityTerzioglu KampusuTR-17100CanakkaleTurkey Data science Nielsen200 W JacksonChicagoIL 60606USA Physics&Astronomy Harper College1200 W Algonquin RdPalatineIL 60067USA Visiting astronomer Mt.John ObservatoryUniversity of CanterburyPrivate Bag 4800Christchurch 8140NZ Carter Observatory Wellington 6012New Zealand school of Chemical&Physical sciences Victoria University of WellingtonWellington 6012New Zealand Variable stars south RASNZPO Box 3181WellingtonNew Zealand

We present combined photometric and spectroscopic analyses of the southern binary star PU ***-resolution spectra of this system were taken at the University of Canterbury *** Observatory in the years 2008 and again in *** find the light contribution of the secondary component to be only 2%of the total light of the system in optical wavelengths,resulting in a single-lined spectroscopic *** TEss data revealed grazing eclipses within the light minima,though the tidal distortion,examined also from Hipparcos data,remains the predominating light curve *** model shows PU Pup to have the more massive primary relatively close to filling its Roche *** Pup is thus approaching the rare‘fast phase’of interactive(Case B)*** adopted absolute parameters are as follows:M_(1)=4.10(±0.20)M_(⊙),M_(2)=0.65(±0.05)M_(⊙),R_(1)=6.60(±0.30)R_(⊙),R_(2)=0.90(±0.10)R_(⊙);T_(1)=11500(±500)K,T_(2)=5000(±350)K;photometric distance=186(±20)pc,age=170(±20)*** less-massive secondary component is found to be significantly oversized and overluminous compared to standard main sequence *** discuss this discrepancy referring to heating from the reflection effect.

关键词： (stars:)binaries(including multiple):close stars:early-type stars:individual(PU Pup) Galaxy:stellar content

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