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Mode of action for inorganic arsenic toxicity and carcinogenesis

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Chinese Science Bulletin 2014年第11期59卷 1078-1082页

作者： Puttappa R.Dodmane lora l.arnold Samuel M.Cohen Department of Pathology and Microbiology University of Nebraska Medical Center983135 Nebraska Medical Center

Inorganic arsenic(iAs) at high doses is a known human carcinogen, inducing tumors of the skin,urinary bladder, and lung. It is also associated with noncancer toxicities. An understanding of the mode of action(MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models,and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity([0.1 lmol/l trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm(1 ppm = 1 mg/l) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, noncancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs.

关键词：体外细胞毒性致癌作用无机砷诱导效应会计准则氧化锌避雷器上皮组织动脉粥样硬化

Transfer learning framework for multi-scale crack type classification with sparse microseismic networks

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International Journal of Mining Science and Technology 2024年第2期34卷 167-178页

作者： arnold Yuxuan Xie Bing Qli Department of Civil and Environmental Engineering Western UniversityLondon N6A 3K7Canada

Rock fracture mechanisms can be inferred from moment tensors(MT)inverted from microseismic ***,MT can only be inverted for events whose waveforms are acquired across a network of *** is limiting for underground mines where the microseismic stations often lack azimuthal ***,there is a need for a method to invert fracture mechanisms using waveforms acquired by a sparse microseismic ***,we present a novel,multi-scale framework to classify whether a rock crack contracts or dilates based on a single *** framework consists of a deep learning model that is initially trained on 2400000+manually labelled field-scale seismic and microseismic waveforms acquired across 692 *** learning is then applied to fine-tune the model on 300000+MT-labelled labscale acoustic emission waveforms from 39 individual experiments instrumented with different sensor layouts,loading,and rock types in *** optimal model achieves over 86%F-score on unseen waveforms at both the lab-and *** model outperforms existing empirical methods in classification of rock fracture mechanisms monitored by a sparse microseismic *** facilitates rapid assessment of,and early warning against,various rock engineering hazard such as induced earthquakes and rock bursts.

关键词： Multi-scale Fracture processes Microseismic Acoustic emission Source mechanism Deep learning

Bayesian network revealing pathways to workplace innovation and career satisfaction in the public service

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Journal of Management Analytics 2020年第2期7卷 253-280页

作者： Warit Wipulanusat Kriengsak Panuwatwanich Rodney A.Stewart Stewart l.arnold Jue Wang logistics and Business Analytics Center of Excellence and School of Engineering and Technology Walailak UniversityNakhonsithammaratThailand School of Civil Engineering and Technology Sirindhorn International Institute of TechnologyThammasat UniversityPathum ThaniThailand School of Engineering and Built Environment Griffith UniversityQueenslandAustralia Nanyang Business School Nanyang Technological UniversitySingapore School of Social Sciences Nanyang Technological UniversitySingapore

This paper examined the innovation process in the Australian Public Service(APS)using a Bayesian network(BN)founded on an empirically derived structural equation *** focus of the BN was to examine the impact of leadership style and organisational culture on workplace innovation and career satisfaction in the *** scenario analysis,the best combination of managerial actions for enhancing APS career satisfaction was *** results emphasise the benefit of encouraging management to adopt a transformational leadership style and instilling innovative culture in their *** addition,innovative culture was a key driver of workplace innovation,which served to improve the career satisfaction of APS *** are discussed to propose practical strategies for organisations wish to encourage innovation among employees.

关键词： innovation public sectors scenario analysis Bayesian network structural equation model

SMIlE soft X-ray Imager flight model CCD370 pre-flight device characterisation

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Earth and Planetary Physics 2024年第1期8卷 25-38页

作者： S.Parsons D.J.Hall O.Hetherington T.W.Buggey T.arnold M.W.J.Hubbard A.Holland Centre for Electronic Imaging the Open UniversityMilton KeynesMK76AAUK

Throughout the SMIlE mission the satellite will be bombarded by radiation which gradually damages the focal plane devices and degrades their *** order to understand the changes of the CCD370s within the soft X-ray Imager,an initial characterisation of the devices has been carried out to give a baseline performance *** CCDs have been characterised,the two flight devices and the flight spa *** has been carried out at the Open University in a bespo ke cleanroom measure ment *** results show that there is a cluster of bright pixels in the flight spa re which increases in size with tempe *** at the nominal ope rating tempe rature(-120℃) it is within the procure ment ***,the devices meet the specifications when ope rating at -120℃ in 6 × 6 binned frame transfer science *** se rial charge transfer inefficiency degrades with temperature in full frame *** any charge losses are recovered when binning/frame transfer is implemented.

关键词： CCD soft X-ray imager characterisation SMIlE

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

晚白垩世真兽类Zalamdalestes揭示哺乳动物独特的枢椎及其复杂的进化过程

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Science Bulletin 2024年第11期69卷 1767-1775页

作者： Patrick arnold Katarzyna Janiszewska 李茜 Jingmai K.O'Connor lucja Fostowicz-Frelik Institute of Biochemistry and Biology University of PotsdamPotsdam D-14476Germany Environmental Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland Key laboratory of Evolutionary Systematics of Vertebrates Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China The Field Museum of Natural History Chicago IL 60605USA Department of Organismal Biology and Anatomy The University of ChicagoChicago IL 60637USA Evolutionary Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland

The typical mammalian neck consisting of seven cervical vertebrae(C1–C7)was established by the late Permian in the cynodont forerunners of modern *** structure is precisely adapted to facilitate movements of the head during feeding,locomotion,predator evasion,and social ***,the clade including crown placentals,has a fossil record extending back more than 125 million years revealing significant morphological diversification in the *** very little is known concerning the early evolution of eutherian cervical morphology and its functional adaptations.A specimen of Zalambdalestes lechei from the late Cretaceous of Mongolia boasts exceptional preservation of an almost complete series of cervical vertebrae(C2–C7)revealing a highly modified axis(C2).The significance of this cervical morphology is explored utilizing an integrated approach combining comparative anatomical examination across mammals,muscle reconstruction,geometric morphometrics and virtual range of motion *** compared the shape of the axis in Zalambdalestes to a dataset of 88 mammalian species(monotremes,marsupials,and placentals)using three-dimensional landmark *** results indicate that the unique axis morphology of Zalambdalestes has no close analog among living *** range of motion analysis of the neck strongly implies Zalambdalestes was capable of exerting very forceful head movements and had a high degree of ventral flexion for an animal its *** findings reveal unexpected complexity in the early evolution of the eutherian cervical morphology and suggest a feeding behavior similar to insectivores specialized in vermivory and defensive behaviors in Zalambdalestes akin to modern spiniferous mammals.

关键词： Atlas Axis Vertebral column Stem placental Morphology paleoecology

The CCD instrument background of the SMIlE SXI

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Earth and Planetary Physics 2024年第1期8卷 15-24页

作者： M.W.J.Hubbard O.Hetherington D.J.Hall T.W.Buggey S.Parsons T.arnold A.Holland C.Pagani S.Sembay Centre for Electronic Imaging The Open UniversityMilton KeynesMK76AAUK X-ray and Observational Astronomy Group Department of Physics&AstronomyUniversity of LeicesterLE17RHUK

The ESA and CAS SMIlE mission orbit is highly elliptical and will pass through multiple radiation *** Soft X-ray Imager(SXI)instrument aboard has a radiation shutter door designed to close when the surrounding radiation flux is *** shutter door will close when passing below an altitude threshold to protect against trapped particles in the Earth’s Van Allen ***,two radiation environments can be approximated based on the shutter door position:open and *** instrument background for the CCDs(Charge-Coupled Devices)that form the focal plane array of the SXI were evaluated for the two *** to the correlation of the space environment with the solar cycle,the solar minima and maxima,the background was also evaluated at these two *** results demonstrated that the highest instrument background will occur during solar minima due to the main contributing source being Galactic Cosmic Rays(GCRs).It was also found that the open background was highest for solar minima and that the closed background was highest during solar *** is due to the radiation shutter door acting as a scattering centre and the changes in the energy flux distribution of the GCRs between the two solar extremes.

关键词： instrument background X-ray astronomy space radiation

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál Department of Physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

On calculating glacial isostatic adjustment

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Geodesy and Geodynamics 2024年第5期15卷 441-452页

作者： l.M.Cathles Cornell University IthacaNY 14853USA

Modeling the earth's fluid and elastic response to the melting of the glaciers of the last ice age is the most direct way to infer the earth's radial viscosity ***,we compare two methods for calculating the viscoelastic response to surface *** one,the elastic equation of motion is converted to a viscoelastic equation using the Correspondence *** the other,elastic deformation is added to the viscous flow as isostatic adjustment *** two modeling methods predict adjustment histories that are different enough to potentially impact the interpretation of the observed glacial isostatic adjustment(GIA).The differences arise from buoyancy and whether fluid displacements are subjected to hydrostatic *** methods agree if they use the same equations and boundary *** origin of the differences is determined by varying the boundary conditions and pre-stress application.

关键词： Glacial isostatic adjustment Viscoelastic normal modes Hydrostatic pre-stress Elastic buoyancy Correspondence principle