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A seed and soil model of loneliness in Alzheimer's disease

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Neural Regeneration Research 2024年第12期19卷 2575-2576页

作者： hannah l.Apostolou Ian m.mcDonough Department of Psychology The University of AlabamaTuscaloosaALUSA Department of Psychology Binghamton UniversityBinghamtonNYUSA

loneliness is classically defined as a result of perceiving a discrepancy between the desired quantity and quality of one's social life and actual social relationships(Perlman and Peplau,1984).lifespan research has indicated older adults are among the highest risk for experiencing loneliness because their social network size decreases more frequently than that of younger adults.

关键词： Alzheimer younger soil

Strategies towards statistically robust interpretations of in situ U-Pb zircon geochronology

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Geoscience Frontiers 2016年第4期7卷 581-589页

作者： Christopher J.spencer Christopher l.Kirkland Richard J.m.Taylor The Institute of Geoscience Research(TIGeR) Department of Applied GeologyWestern Australian School of MinesCurtin UniversityWA 6102Australia Centre for Exploration Targeting-Curtin Node Department of Applied GeologyWestern Australian School of MinesCurtin UniversityWA 6102Australia Australian Research Council Centre of Excellence for Core to Crust Fluid SystemsPerthWA 6102Australia

Zircon U-Pb geochronology has become a keystone tool across Earth science, arguably providing the gold standard in resolving deep geological time. The development of rapid in situ analysis of zircon （via laser ablation and secondary ionization mass spectrometry） has allowed for large amounts of data to be generated in a relatively short amount of time and such large volume datasets offer the ability to address a range of geological questions that would otherwise remain intractable （e.g. detrital zircons as a sedi- ment fingerprinting method）. The ease of acquisition, while bringing benefit to the Earth science com- munity, has also led to diverse interpretations of geochronological data. In this work we seek to refocus U -Pb zircon geochronology toward best practice by providing a robust statistically coherent workflow. We discuss a range of data filtering approaches and their inherent limitations （e.g. discordance and the reduced chi-squared; mSWD）. We evaluate appropriate mechanisms to calculate the most geologically appropriate age from both 238U/206pb and 207pb/206pb ratios and demonstrate the cross over position when chronometric power swaps between these ratios. As our in situ analytical techniques become progressively more precise, appropriate statistical handing of U-Pb datasets will become increasingly pertinent.

关键词： Zircon Geochronology U-Pb Geostatistics mSWD

Regulation of enolase activation to promote neural protection and regeneration in spinal cord injury

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Neural Regeneration Research 2023年第7期18卷 1457-1462页

作者： hannah mmcCoy Rachel Polcyn Naren lBanik Azizul Haque Department of microbiology and Immunology Medical University of South CarolinaCharlestonSCUSA Department of Neurosurgery Medical University of South CarolinaCharlestonSCUSA Ralph H.Johnson Veterans Administration medical Center CharlestonSCUSA

Spinal cord injury(SCI)is a debilitating condition characterized by damage to the spinal cord resulting in loss of function,mobility,and sensation with no *** and Drug Administration-approved ***,a multifunctional glycolytic enzyme upregulated after SCI,promotes pro-and anti-inflammatory events and regulates functional recovery in *** is normally expressed in the cytosol,but the expression is upregulated at the cell surface following cellular injury,promoting glial cell activation and signal transduction pathway ***-induced microglia activation triggers pro-inflammatory mediators at the injury site,activating other immune cells and metabolic events,i.e.,Rho-associated kinase,contributing to the neuroinflammation found in *** surface expression also activates cathepsin X,resulting in cleavage of the C-terminal end of neuron-specific enolase(NSE)and non-neuronal enolase(NNE).Fully functional enolase is necessary as NSE/NNE C-terminal proteins activate many neurotrophic processes,i.e.,the plasminogen activation system,phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B,and mitogen-activated protein kinase/extracellular signal-regulated *** here suggest an enolase inhibitor,ENOblock,attenuates the activation of Rho-associated kinase,which may decrease glial cell activation and promote functional recovery following ***,ENOblock inhibits cathepsin X,which may help prevent the cleavage of the neurotrophic C-terminal protein allowing full plasminogen activation and phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase *** combined NSE/cathepsin X inhibition may serve as a potential therapeutic strategy for preventing neuroinflammation/degeneration and promoting neural cell regeneration and recovery following *** role of cell membrane-expressed enolase and associated metabolic events should be investigated to determine if the same strategies can be applied to other neu

关键词： cathepsin X ENOblock enolase glia mitogen-activated protein kinase/extracellular signal-regulated kinase neurodegeneration neuroinflammation phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B Rho-associated protein kinase spinal cord injury

Deconvolving the pre-Himalayan Indian margin-Tales of crustal growth and destruction

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Geoscience Frontiers 2019年第3期10卷 863-872页

作者： Christopher J.spencer Brendan Dyck Catherine m.mottram Nick m.W.Roberts Wei-Hua Yao Erin l.martin Earth Dynamics Research Group The Institute for Geoscience Research (TIGeR) Department of Applied Geology Curtin University NERC Isotope Geosciences laboratory British Geological Survey Department of Earth Sciences Simon Fraser University University Drive Department of Environment Earth and Ecosystems The Open UniversityWalton Hall Milton Keynes MK7 6AA UK School of Earth and Environmental Sciences University of Portsmouth Schoolof Earth Sciences and Engineering SunYat-sen University

The metamorphic core of the Himalaya is composed of Indian cratonic rocks with two distinct crustal affinities that are defined by radiogenic isotopic geochemistry and detrital zircon age spectra. One is derived predominantly from the Paleoproterozoic and Archean rocks of the Indian cratonic interior and is either represented as metamorphosed sedimentary rocks of the lesser Himalayan Sequence(lHS) or as slices of the distal cratonic margin. The other is the Greater Himalayan Sequence(GHS) whose provenance is less clear and has an enigmatic affinity. Here we present new detrital zircon Hf analyses from lHS and GHS samples spanning over 1000 km along the orogen that respectively show a striking similarity in age spectra and Hf isotope ratios. Within the GHS, the zircon age populations at 2800-2500 ma,1800 ma, 1000 ma and 500 ma can be ascribed to various Gondwanan source regions; however, a pervasive and dominant Tonianage population(～860-800 ma) with a variably enriched radiogenic Hf isotope signature(eHf = 10 to-20) has not been identified from Gondwana or peripheral accreted terranes. We suggest this detrital zircon age population was derived from a crustal province that was subsequently removed by tectonic erosion. Substantial geologic evidence exists from previous studies across the Himalaya supporting the Cambro-Ordovician Kurgiakh Orogeny. We propose the tectonic removal of Tonian lithosphere occurred prior to or during this Cambro-Ordovician episode of orogenesis in a similar scenario as is seen in the modern Andean and Indonesian orogenies, wherein tectonic processes have removed significant portions of the continental lithosphere in a relatively short amount of time. This model described herein of the pre-Himalayan northern margin of Greater India highlights the paucity of the geologic record associated with the growth of continental crust. Although the continental crust is the archive of Earth history, it is vital to recognize the ways in which preservation

关键词： Himalaya Gondwana Zircon Subduction erosion

Strategies towards robust interpretations of in situ zircon lu-Hf isotope analyses

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Geoscience Frontiers 2020年第3期11卷 843-853页

作者： C.J.spencer C.l.Kirkland N.m.W.Roberts N.J.Evans J.liebmann School of Earth and Planetary Sciences The Institute for Geoscience Research(TIGeR)Curtin UniversityPerthAustralia Department of Geological Sciences and Geological Engineering Queen’s UniversityKingstonCanada Centre for Exploration Targeting-Curtin Node The Institute for Geoscience ResearchSchool of Earth and Planetary SciencesCurtin UniversityPerthAustrali Geochronology and Tracers Facility British Geological SurveyNottinghamUK John de laeter Centre GeoHistory Facility School of Earth and Planetary SciencesCurtin UniversityPerthAustralia

The combination of U-Pb and lu-Hf compositions measured in zircon crystals is a remarkably powerful isotopic couplet that provides measures on both the timing of mineral growth and the radiogenic enrichment of the source from which the zircon *** U-Pb age documents the timing of zircon crystallization/recrystallization and Hf isotopes inform on the degree to which the host melt was derived from a radiogenic reservoir(*** mantle) versus an unradiogenic reservoir(*** continental crust),or some mixture of these *** ease of generating large quantities of zircon U-Pb and lu-Hf data has been in large part facilitated by instrument ***,the dramatic increase in time constrained zircon lu-Hf analyses in the Earth science community has brought to the fore the importance of careful data collection and reduction workflows,onto which robust geological interpretations may be *** this work,we discuss the fundamentals of lu-Hf isotopes in zircon,which then allows us to provide a robust,accessible,methodology for the assessment of data ***,we discuss some novel techniques for:data visualization—that facilitates better transparency of data interpretation;integration of geographic information—that may reveal spatial trends where temporal trends were only apparent before;and some novel statistical evaluation tools—that may provide more rigorous interand intra-sample comparisons.

关键词： Zircon Geochronology Isotope geochemistry lu-Hf isotopes Geostatistics Data visualization

O_(2)-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

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Chinese Chemical letters 2024年第7期35卷 394-399页

作者： Yu Qin mingyang Huang Chenlu Huang hannah lPerry linhua Zhang Dunwan Zhu Tianjin Key laboratory of Biomedical materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China molecular Sciences Research Hub Department of ChemistryWhite City CampusImperial College LondonLondon W120BZUnited Kingdom

Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor ***,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor *** drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective *** address these issues,a mnO_(2)doped nano-delivery system(HTIm-Pms)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and mnO_(2)*** surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell *** internalization,HTIm-Pms showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the mnO_(2)and *** released mnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT *** PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS *** PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of *** promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.

关键词： Photodynamic therapy Photothermal therapy Oxygen generating One-step self-assembly Stimuli-responsive nanoparticles

Cs_(3)Bi_(2)l_(9)-hydroxyapatite composite waste forms for cesium and iodine immobilization

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Journal of Advanced Ceramics 2022年第5期11卷 712-728页

作者： Kun YANG Yachun WANG Junhua SHEN spencer m.SCOTT Brian J.RIlEY John D.VIENNA Jie lIAN Department of mechanical Aerospaceand Nuclear EngineeringRensselaer Polytechnic InstituteTroyUSA Department of materials Science&Engineering Rensselaer Polytechnic InstituteTroyUSA Savannah River National laboratory AikenUSA Pacific Northwest National laboratory RichlandUSA

Perovskite-based ceramic composites were developed as potential waste form materials for immobilizing cesium(Cs)and iodine(I)with high waste loadings and chemical *** perovskite Cs_(3)Bi_(2)I_(9)has high Cs(22 wt%)and I(58 wt%)content,and thus can be used as a potential host phase to immobilize these critical *** this work,the perovskite Cs_(3)Bi_(2)I_(9)phase was synthesized by a cost effective solution-based approach,and was embedded into a highly durable hydroxyapatite matrix by spark plasma sintering to form dense ceramic composite waste *** chemical durabilities of the monolithic Cs_(3)Bi_(2)I_(9)and Cs_(3)Bi_(2)I_(9)-hydroxyapatite composite pellets were investigated by static and semi-dynamic leaching tests,*** and I are incongruently released from the matrix for both pure Cs_(3)Bi_(2)I_(9)and composite *** normalized Cs release rate is faster than that of I,which can be explained by the difference in the strengths between Cs-I and Bi-I bonds as well as the formation of insoluble micrometer-sized BiOI *** activation energies of elemental releases based on dissolution and diffusion-controlled mechanisms are determined with significantly higher energy barriers for dissolution from the composite versus that of the monolithic Cs_(3)Bi_(2)I_(9).The ceramic-based composite waste forms exhibit excellent chemical durabilities and waste loadings,commensurate with the state-of-the-art glass-bonded perovskite composites for I and Cs immobilization.

关键词： cesium(Cs) iodine(Ⅰ) perovskite nuclear waste hydroxyapatite

Evolutionary Genomics of Plant Gametophytic Selection

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Plant Communications 2020年第6期1卷 18-33页

作者： Felix E.G.Beaudry Joanna l.Rifkin spencer C.H.Barrett Stephen I.Wright Department of Ecology and Evolutionary Biology The University of Toronto25 Willcocks StreetTorontoON M5S 3B2Canada These authors contributed equally to this article

It has long been recognized that natural selection during the haploid gametophytic phase of the plant life cycle may have widespread importance for rates of evolution and the maintenance of genetic *** theoretical advances have further highlighted the significance of gametophytic selection for diverse evolutionary *** approaches offer exciting opportunities to address key questions about the extent and effects of gametophytic selection on plant evolution and ***,we review the progress and prospects for integrating functional and evolutionary genomics to test theoretical predictions,and to examine the importance of gametophytic selection on genetic diversity and rates of *** is growing evidence that selection during the gametophyte phase of the plant life cycle has important effects on both gene and genome evolution and is likely to have important pleiotropic effects on the *** discuss the opportunities to integrate comparative population genomics,genome-wide association studies,and experimental approaches to further distinguish how differential selection in the two phases of the plant life cycle contributes to genetic diversity and adaptive evolution.

关键词： gametophyte pollen ovule evolution genomics selection

Evaluating the physicochemical effects of conjugating peptides into thermogelling hydrogels for regenerative biomaterials applications

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Regenerative Biomaterials 2021年第6期8卷 260-272页

作者： hannah A.Pearce Emily Y.Jiang Joseph W.R.Swain Adam m.Navara Jason l.Guo Yu Seon Kim Andrew Woehr Jeffrey D.Hartgerink Antonios G.mikos Department of Bioengineering Rice University6500 Main StreetHoustonTX 77030USA Depatment of Chemistry Rice University6500 Main StreetHoustonTX 77030USA

Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial ***,our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol),which crosslinks P(NiPAAm-co-glycidyl methacrylate)via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click *** study’s aim was to evaluate the impact of peptides on the physicochemical properties of the *** physicochemical properties of the hydrogels including the lower critical solution temperature,crosslinking times,swelling,degradation,peptide release and cytocompatibility were *** gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel *** sol fractions were found for all groups,indicating that inclusion of peptides does not impact ***,the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic *** hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over *** study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of *** characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.

关键词： thermogelling click chemistry hydrogels peptides poly(N-isopropylacrylamide)