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Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

World Journal of Gastroenterology 2018年第48期24卷 5418-5432页

作者： sandra Wagner Christina s Mullins michael Linnebacher section of Molecular Oncology and Immunotherapy General SurgeryUniversity Medical Center

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

关键词： Cancer vaccines Colorectal neoplasm Immunotherapy Neoplasm antigen tumor-associated antigens tumor-specific antigens Neoantigen(s)

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Empirical analysis for the characterization of geo-mechanical strength and pressure regime:Implications on hydraulic fracturing stimulation

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Petroleum 2019年第3期5卷 260-270页

作者： Dorcas s.Eyinla michael A.Oladunjoye Department of Earth sciences Adekunle Ajasin UniversityNigeria Department of Geology University of IbadanNigeria

Among the several activities involved in oil exploration are the determination of hydrocarbon in-place and mechanical competency of the oil *** pressure regimes of the formation have also become vital properties which must be well known to ensure preliminary awareness of the hydraulic *** study seeks to adopt a prediction strategy of the overall geo-mechanical competency and strength of the formation,using a less stressful computational process and an empirical analysis,developed using three wells from ED BON area in parts of Niger *** constants such as Poisson Ratio,Young's,shear and Bulk moduli which are the parameters for characterizing rock mechanical properties were estimated,as well as the subsurface formation pressures and the associated fracture gradient using P-wave sonic and density *** results from the analysis showed that there is correlation between elastic strength and fracture pressure.

关键词： Elastic strength Hydraulic fracturing Competency Prediction strategy Geomechanical parameters

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C:N:P stoichiometry and nutrient limitation of the soil microbial biomass in a grazed grassland site under experimental P limitation or exces

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Ecological Processes 2012年第1期1卷 66-76页

作者： Bryan s Griffiths Annette spilles michael Bonkowski Teagasc Environment Research CentreJohnstown CastleWexfordCoWexfordIreland Current address:sAC King's BuildingsWest Mains RoadEdinburgh EH93JGUK Mathematisch Naturwissenschaftliche Fakultät der Universität zu Köln Zoologisches Institut Abt.TerrestrischeÖkologieBiowissenschaftliches ZentrumOtto-Fischer-Str.6D-50674KölnGermany

Introduction:The availability of essential nutrients,such as nitrogen(N)and phosphorus(P),can feedback on soil carbon(C)and the soil microbial *** cycles can be supplemented by agricultural fertiliser addition,and we determined whether the stoichiometry and nutrient limitation of the microbial biomass could be affected by an unbalanced nutrient ***:samples were taken from a long-term trial(in effect since 1968)with annual applications of 0,15 and 30 kg P ha^(−1) with constant N and *** and microbial biomass CNP contents were measured and nutrient limitation assessed by substrate-induced *** regression and discriminant analyses were used to identify the variables explaining nutrient ***:soil and biomass CNP increased with increasing P fertiliser,and there was a significant,positive,correlation between microbial biomass P and biomass C,apart from at the highest level of P fertilisation when the microbial biomass was over-saturated with *** molar ratios of C:N:P in the microbial biomass remained constant(homeostatic)despite large changes in the soil nutrient *** growth was generally limited by C and N,except in soil with no added P when C and P were the main limiting nutrients.C,N and P,however,did not explain all the growth limitation on the soils with no added ***:Increased soil C and N were probably due to increased net primary *** results confirm that C:N:P ratios within the microbial biomass were constrained(***)under near optimum soil *** with no added P were characterised by strong microbial P limitation and soils under high P by over-saturation of microorganisms with *** changes in biomass C:P can be indicative of nutrient limitation within a site.

关键词： Carbon Nitrogen Nutrient limitation Phosphorus soil microbial biomass stoichiometry

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sEMILINEAR HEMIVARIATIONAL INEQUALITIEs WITH sTRONG REsONANCE AT INFINITY

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Acta Mathematica scientia 2006年第1期26卷 59-73页

作者： michael Filippakis Leszek Gasi■ski Nikolaos s.Papageorgiou Department of Mathematics National Technical University Zografou CampusAthens 15780Greece Institute of Computer science Jagiellonian University ul.Nawojki 1130072 CracowPoland

A semilinear elliptic equation with strong resonance at infinity and with a nonsmooth potential is studied. Using nonsmooth critical point theory and developing some abstract minimax principles which complement and ex... 详细信息

关键词： strong resonance hemivariational inequality Laplacian principal eigenvalue locally Lipschitz function Clarke subdifferential nonsmooth criticalpoint theory

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Flavonoids:New Roles for Old Molecules

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Journal of Integrative Plant Biology 2010年第1期52卷 98-111页

作者： Charles s. Buer Nijat Imin michael A. Djordjevic Genomic Interactions Group ARC Centre of Excellence for Integrative Legume Research Research School of Biology College of Medicine Biology and Environment The Australian National University

Flavonoids are ubiquitous in the plant kingdom and have many diverse functions including defense, UV protection, auxin transport inhibition, allelopathy, and flower coloring. Interestingly, these compounds also have considerable biological activity in plant, animal and bacterial systems - such broad activity is accomplished by few compounds. Yet, for all the research over the last three decades, many of the cellular targets of these secondary metabolites are unknown. The many mutants available in model plant species such as Arabidopsis thaliana and Medicago truncatula are enabling the intricacies of the physiology of these compounds to be deduced. In the present review, we cover recent advances in flavonoid research, discuss deficiencies in our understanding of the physiological processes, and suggest approaches to identify the cellular targets of flavonoids.

关键词： Flavonoids DPBA Figure TTG root

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Consumption of rice and fish in an electronic waste recycling area contributes significantly to total daily intake of mercury

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Journal of Environmental sciences 2015年第12期27卷 83-86页

作者： Hanyong Peng michael s.Reid X.Chris Le Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyUniversity of Alberta

Mercury is a global pollutant due to its widespread use,emission,and long-range transport（Blum,2013;Pacyna et al.,2010）.It is considered a priority pollutant due to its neurological toxicity,persistence,and bioaccumulation（Pacyna et al.,2010;sharma et al.,2015）.Mercury pollution can occur when products that contain mercury are improperly disposed of and mercury is released into the air,water,and soil（Zhang and Wong,2007）.An estimated 22%of the annual world usage of mercury is in electrical equipment such as batteries,thermometers,and discharge lamps,and electronic devices such as monitors and

关键词： Mercury Methyl mercury Electronic waste Biomonitoring Dietary intake Human exposure assessment Environmental health

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Experience with intraoperative radiotherapy for breast cancer: the Geneva University Hospital's experience

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Chinese Journal of Cancer Research 2016年第4期28卷 463-466页

作者： Emanuela Esposito michael Douek Division of Cancer studies King's College London Department of Breast surgery Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"–IRCCS

Background Breast conserving surgery along with adjuvant radiotherapy is effective in terms of local control and survival for early- stage breast cancer （1）. External beam radiotherapy （EBRT） following breast conserving surgery has been shown to improve survival by preventing local recurrence, in the Early Breast Cancer Trialists＇ Collaborative Group meta-analysis （2）. standard radiotherapy typically requires numerous fractions over a 3-5 week period and is performed weeks or months after surgery or chemotherapy.

关键词： IORT Experience with intraoperative radiotherapy for breast cancer the Geneva University Hospital’s experience

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Lactate is a potentially harmful substitute for brain glucose fuel:consequences for metabolic restoration of neurotransmission

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Neural Regeneration Research 2025年第5期20卷 1403-1404页

作者： Oliver Kann Lennart soder Babak Khodaie Institute of Physiology and Pathophysiology Heidelberg UniversityHeidelbergGermany Interdisciplinary Center for Neurosciences(IZN) Heidelberg UniversityHeidelbergGermany

The metabolite lactate (L-lactate) can be generated and released by diverse brain cells,including neurons,astrocytes,and oligodendrocytes (Kann,2023;Rae et al.,2024).Lactate production usually requires the degradation of glucose (D-glucose)-and glycogen in astrocytes-to pyruvate by glycolysis and subsequent conversion of pyruvate to lactate by the enzyme lactate dehydrogenase(Figure 1A;Dienel,2019;Rae et al.,2024).

关键词： consequences Figure restoration

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Activation of 2D Mos_(2) electrodes induced by high-rate lithiation processes

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Journal of Energy Chemistry 2023年第3期78卷 56-70,I0003页

作者： Tianzhu Liu Georgian Melinte Oleksandr Dolotko michael Knapp Beatriz Mendoza-sánchez Institute for Applied Materials-Energy storage systems(IAM-Ess) Karlsruhe Institute of Technology(KIT)Eggenstein-Leopoldshafen D-76344Germany Karlsruhe Nano Micro Facility(KNMF) Karlsruhe Institute of Technology(KIT)Eggenstein-Leopoldshafen D-76344Germany Helmholtz-Institute Ulm for Electrochemical Energy storage(HIU) Ulm 89081Germany

Mos_(2) is a highly promising material for application in lithium-ion battery anodes due to its high theoretical capacity and low ***,problems with a fast capacity decay over cycling,especially at the first cycles,and poor rate performance have deterred its practical ***,electrodes comprised solely of few-layers 2D Mos_(2) nanosheets have been manufactured by scalable liquid-phase exfoliation and spray deposition *** long-standing controversy questioning the reversibility of conversion processes of Mos_(2)-based electrodes was *** studies revealed that,in 2D Mos_(2) electrodes,conversion processes are indeed reversible,where nanostructure played a key *** of the electrodes at high current rates revealed an intriguing phenomenon consisting of a continuously increasing capacity after ca.100-200 *** phenomenon was comprehensively addressed by a variety of electrochemical and microscopy methods that revealed underlying physical activation mechanisms that involved a range of profound electrode structural *** mechanisms delivered a capacitive electrode of a superior rate performance and cycling stability,as compared to the corresponding pristine electrodes,and to Mos_(2) electrodes previously ***,we have devised a methodology to overcome the problem of cycling stability of 2D Mos_(2) ***,activation of electrodes constitutes a methodology that could be applied to enhance the energy storage performance of electrodes based on other 2D nanomaterials,or combinations thereof,strategically combining chemistries to engineer electrodes of superior energy storage properties.

关键词： 2D Mos_(2) Liquid-phase exfoliation spray-deposition Conversion processes Activation mechanisms Energy storage mechanisms

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Modelling mitochondrial dysfunction in Alzheimer’s disease using human induced pluripotent stem cells

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World Journal of stem Cells 2019年第5期11卷 236-253页

作者： Kate Elizabeth Hawkins michael Duchen Cell and Developmental Biology Division of Biosciences University College London

Alzheimer’s disease (AD) is the most common form of dementia. To date, only five pharmacological agents have been approved by the Food and Drug Administration for clinical use in AD, all of which target the symptoms of the disease rather than the cause. Increasing our understanding of the underlying pathophysiology of AD will facilitate the development of new therapeutic strategies. Over the years, the major hypotheses of AD etiology have focused on deposition of amyloid beta and mitochondrial dysfunction. In this review we highlight the potential of experimental model systems based on human induced pluripotent stem cells (iPsCs) to provide novel insights into the cellular pathophysiology underlying neurodegeneration in AD. Whilst Down syndrome and familial AD iPsC models faithfully reproduce features of AD such as accumulation of Aβ and tau, oxidative stress and mitochondrial dysfunction, sporadic AD is much more difficult to model in this way due to its complex etiology. Nevertheless, iPsC-based modelling of AD has provided invaluable insights into the underlying pathophysiology of the disease, and has a huge potential for use as a platform for drug discovery.

关键词： Induced pluripotent stem cells Alzheimer's disease Mitochondria

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