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A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

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Translational Neurodegeneration 2023年第1期12卷 568-571页

作者： Kelsie M.LaBarbera Yvette I.Sheline Nicholas J.Izzo Carla M.Yuede Lora Waybright Raymond Yurko Hannah M.Edwards Woodrow D.Gardiner Kaj Blennow Henrik Zetterberg Anne Börjesson-Hanson Roger Morgan Charles S.Davis Robert J.Guttendorf Lon S.Schneider Steven DeKosky harry levine iii Michael Grundman Anthony O.Caggiano John R.Cirrito Susan M.Catalano Mary E.Hamby Cognition Therapeutics Inc. PittsburghPAUSA University of Pennsylvania PhiladelphiaUSA Washington University St.LouisUSA University of Gothenburg MölndalSweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden Clinical Neurochemistry Laboratory Sahlgrenska University HospitalMölndalSweden Department of Neurodegenerative Disease UCL Institute of NeurologyQueen SquareLondonUK UK Dementia Research Institute at UCL LondonUK Hong Kong Center for Neurodegenerative Diseases Clear Water BayHong KongChina Wisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWIUSA Karolinska University Hospital StockholmSweden MedSurgPI LLCRaleighNCUSA CSD Biostatistics Inc.Oro ValleyAZUSA Aclairo Pharmaceutical Development Group IncViennaVAUSA Keck School of Medicine of USC Los AngelesCAUSA McKnight Brain Institute University of FloridaGainesvilleFLUSA Sanders-Brown Center on Aging University of KentuckyLexingtonKYUSA Global R&D Partners LLCSan DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoUSA

Trial Registration:May 11th,2018 *** Identifier:NCT03522129 https://clini caltr ***/ct2/show/*** therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet *** evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].

关键词： Alzheimer Aβ damage

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Assessment of corrected time-step method for nominal ionospheric gradient calculation: A comparative analysis with spatial approaches

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Earth and Planetary Physics 2024年第4期8卷 641-649页

作者： Slamet Supriadi Prayitno Abadi Susumu Saito harry Bangkit Dwiko Unggul Prabowo Adi Purwono Ginaldi Ari Nugroho Research Center for Smart Mechatronics National Research and Innovation Agency(BRIN)BandungIndonesia Research Center for Climate and Atmosphere BRINBandungIndonesia School of Electrical Engineering Telkom UniversityKab.BandungIndonesia Electronic Navigation Research Institute National Institute of MaritimePort and Aviation TechnologyTokyoJapan Research Center for Space BRINBandungIndonesia

The effect of ionospheric delay on the ground-based augmentation system under normal conditions can be mitigated by determining the value of the nominal ionospheric gradient(σvig).The nominal ionospheric gradient is generally obtained from Continuously Operating Reference Stations data by using the spatial single-difference method(mixed-pair,station-pair,or satellite-pair)or the temporal single-difference method(time-step).The time-step method uses only a single receiver,but it still contains ionospheric temporal *** introduce a corrected time-step method using a fixed-ionospheric pierce point from the geostationary equatorial orbit satellite and test it through simulations based on the global ionospheric *** also investigate the effect of satellite paths on the corrected time-step method in the region of the equator,which tends to be in a more north–south direction and to have less coverage for the east–west ionospheric *** study also addresses the limitations of temporal variation correction coverage and recommends using only the correction from *** processes are developed under simulations because observational data are still difficult to *** findings demonstrate that the corrected time-step method yieldsσvig values consistent with other approaches.

关键词： ground-based augmentation system nominal ionospheric gradient time-step correction global ionospheric model

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Formation of carbon and oxygen rich surface layer on high purity magnesium by atmospheric carbon dioxide plasma

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Journal of Magnesium and Alloys 2023年第1期11卷 88-99页

作者： Gyoung G.Jang Sinchul Yeom Jong K.Keum Mina Yoon harry iii Meyer Yi-Feng Su Jiheon Jun Manufacturing Science Division Oak Ridge National Laboratory(ORNL)One Bethel Valley RoadPO Box 2008MS6054Oak RidgeTN 37831United States Material Science and Technologies Division Oak Ridge National Laboratory(ORNL)One Bethel Valley RoadOak RidgeTN 37831United States Neutron Scattering Division&Center for Nanophase Materials Sciences ORNLOne Bethel Valley RoadOak RidgeTN 37831United States Chemical Sciences Division ORNLOne Bethel Valley RoadOak RidgeTN 37831United States

Carbon and oxygen-rich corrosion barrier layer formed on Mg by a simple and scalable CO_(2) atmospheric plasma(CO_(2)-AP)*** reactive CO_(2)-AP interacts with the Mg surface and forms a unique layered structure with the top MgCO_(3)/MgO-intermixed particulates pillars and the bottom dense *** surface features were simultaneously formed on the nano-/micro-structured MgO layer by carbonate molecules,plasma-active CO_(2) molecules,and/or other volatile organic compounds on the nano-/micro-structured MgO particle *** resulting surfaces after CO_(2)-AP were either hydrophobic or hydrophilic and exhibited lower anodic current or high resistance for Mg *** the hydrophobic surfaces of CO_(2)-AP treated Mg,molecular dynamic simulations were performed to understand the origin of hydrophobicity and identified that the amorphous carbon layers formed on the Mg surface are the *** environmentally benign abundant-gas-based process enables the cost reduction associated with waste treatment,generation of by-product,and supply of raw material.

关键词： Atmospheric plasma Magnesium Corrosion protection Surface modification

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The many faces of p53:something for everyone

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Journal of Molecular Cell Biology 2019年第7期11卷 524-530页

作者： Arnold J.levine Institute for Advanced Study PrincetonNJ 08540USA

The p53 gene,from discovery to classification:the first 10 years Forty years ago four research laboratories in London,Paris,NewYork/Bethesda,and Princeton uncovered the existence of the p53 protein (Deleo et al.,1979;Lane and Crawford,1979;Linzer and levine,1979;Kress et al.,1979).Each laboratory came upon this protein for a different reason and with a different experimental approach that uncovered this unanticipated ***,the four papers permitted one to con elude the following:(i) in SV40-infected and transformed cells the SV40-e ncoded on cogene protein,the large T-antigen,formed a protein complex with a cellular-encoded protein of -53000 daltons in size,(ii) This p53 protein was detected at high levels in a variety of transformed cells derived from viral,chemical,or inherited (teratocarcinomas) transformation events,(iii) Nontransformed cells expressed lower levels of the p53 protein,(iv) Animals bearing tumors produced antibodies directed against the p53 protein.

关键词： discovery years protein

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Notes on the ＂Note＂： The Eigo Note

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Sino-US English Teaching 2011年第10期8卷 629-639页

作者： harry F. Carley iii Matsuyama University Ehime Prefecture Japan

This paper evaluates the lessons that comprise the Japanese Governments English language text for 5th and 6th grade primary school students. The Eigo Note has been formal introducted from April 2011. It is needless to say that the prime purpose of English textbooks is to help students acquire linguistic knowledge and skills （Yuasa, 2010, p. 154）. This assessment was accomplished through the early introduction of the Eigo Note over the 2009-2010 Japanese school year. The assignment of letter grades, A-F, as commonly prescribed in the United States school system, was given to each unit based on the author＇s past and present teaching experience of over 20 years in the Japanese school system. Concluding remarks contain comments and suggestions for Japanese team teaching in the Eigo Note instructional environment

关键词： Eigo Note English education Japanese primary school

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The Alpe Arami Story: Triumph of Data over Prejudice

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Journal of Earth Science 2010年第5期21卷 731-743页

作者： harry W Green II Larissa F Dobrzhinetskaya Krassimir N Bozhilov Institute of Geophysics and Planetary Physics Department of Earth Sciences University of California at Riverside Riverside CA92521 USA Department of Earth Sciences University of California at Riverside Riverside CA92521 USA

The Alpe Arami garnet peridotite of the Southern Swiss Alps is associated with eclogites and included within quartzofeldspathic gneisses. Controversy has swirled around the depth of origin of this massif since the 1970s when application of the newly-developed technique of thermobarometry suggested a depth of last equilibration of greater than 120 kin. Such controversy accelerated in 1996 when we reported microstructural evidence of extensive precipitation of ilmenite and spinel from olivine and proposed a much greater depth of origin. Subsequent experiments showed that it was possible to dissolve the observed amount of TiO2 in olivine, but only at depths in excess of 300 kin, agreeing with the earlier proposal. In 1999 we added new, independent, evidence concerning exsolution of high-pressure clinoenstatite from diopside that in-and-of-itself required a depth of origin in excess of 250 km. Subsequently, we also added evidence from the surrounding eclogites of very high pressures and experimental evidence that the pyroxenes included in the amoeboid garnets of this rock had exsolved from a majoritic parent at perhaps even greater pressures. In refutation of the first two of these observations, suggestions were made that （i） we had made a serious error in our estimate of how much ilmenite was present in olivine （and therefore how much TiO2 had been dissolved in olivine）; （ii） the ilmenite had not been exsolved from olivine but former titanian clinohumite had been present and broke down to yield the ilmenite; （iii） the pyroxene exsolved from diopside had been high-temperature clinoenstatite. In all three of these cases, the alternatives offered were claimed to be accommodated at low pressures. Here we review the essence of this controversy and show that the only scenario that can explain all of the data is the one that we originally proposed; indeed, the more recent data have strongly supported that interpretation and pushed the minimum origin of the massif to depths ap

关键词： Alpe Arami TiO2 in olivine high-pressure clinoenstatite deep exhumation.

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荷电雨滴的碰撞

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气象科技 1990年第4期18卷 60-65页

作者： harry T.Ochs iii Robert R.Czys 陈锡铭美国伊利诺斯州水资源调查所

云滴碰撞结果对降水的演变十分重要.碰撞雨滴是并合还是分离,电荷起着决定性作用.在实验室里用以终速自由下落的荷电滴做了实验,揭示了滴碰撞的许多新特点.

关键词：荷电碰撞角自由下落云滴电荷量反电荷频闪灯滴流计算机控制云中

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Vole preference of bilberry along gradients of simulated moose density and site productivity

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Integrative Zoology 2011年第4期6卷 341-351页

作者： Simen PEDERSEN harry P.ANDREASSEN Inga-Lill PERSSON Riitta JULKUNEN-TIITTO Kjell DANELL Christina SKARPE Department of Forestry and Wildlife Management Hedmark University CollegeKoppangNorway Department of Biology Norwegian University of Science and TechnologyTrondheimNorway Department of Wildlife Fish and Environmental StudiesSwedish University of Agricultural SciencesUmeåSweden Department of Biology University of Eastern FinlandJoensuuFinland

Browsing by large herbivores might either increase or decrease preference for the plant by other herbivores,depending on the plant *** a cafeteria test,we studied the preference by root voles(Microtus oeconomus[Pallas,1776])for bilberry(Vaccinium myrtillus L.)previously subjected to 4 levels of simulated moose(Alces alces[Linnaeus,1758])*** different levels of moose density were simulated at population densities relevant for Fennoscandian conditions,in exclosures situated along a site productivity *** expected:(i)voles to prefer bilberry from high productivity sites over low productivity sites;(ii)voles to prefer browsed bilberry,if plants allocate resources to compensatory growth or to avoid browsed bilberry if plants allocate resources to defense;(iii)these effects to increase with increasing simulated moose density;and(iv)the concentration of plant chemicals and the plant morphology to explain vole ***,we predicted that voles would prefer:(i)plants with high nitrogen content;(ii)plants with low content of defensive substances;and(iii)tall plants with long *** preferred bilberry from the high productivity sites compared to the low productivity *** also found an interaction between site productivity and simulated moose density,where voles preferred unbrowsed plants at low productivity sites and intermediate levels of browsing at high productivity *** was no effect of plant chemistry or morphology on vole *** conclude that moose browsing impacts the food preference of *** the current high densities of moose in Fennoscandia,this could potentially influence vole food selection and population dynamics over large geographical areas.

关键词： browsing cervid herbivory induced defense Microtus

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Clinical characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital

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Cancer Biology & Medicine 2020年第1期17卷 199-207页

作者： Xiaonan Cui Daiwei Han Marjolein AHeuvelmans Yihui Du Yingru Zhao Lei Zhang harry JMGroen Geertruida Hde Bock Monique DDorrius Matthijs Oudkerk Rozemarijn Vliegenthart Zhaoxiang Ye Department of Radiology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Radiology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Epidemiology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Medisch Spectrum Twente Department of PulmonologyEnschede 7512 KZThe Netherlands Department of Thoracic Surgery Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Pulmonary Diseases University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands University of Groningen University Medical Center GroningenGroningen 9713 GZThe Netherlands

Objectives:To evaluate the characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer ***:Patients with pulmonary nodules 4–25 mm in diameter detected via computed tomography(CT)in 2013 were consecutively *** analysis was restricted to patients with a histological nodule diagnosis or a 2-year follow-up period without nodule growth confirming benign *** information was collected from hospital ***:Among the 314 nodules examined in 299 patients,212(67.5%)nodules in 206(68.9%)patients were *** to benign nodules,malignant nodules were larger(18.0 mm vs.12.5 mm,Piii or IV]and 66 as *** 36 nodules(11.5%),diagnosis was confirmed by biopsy and the remainder verified based on stability of nodule size at follow-up imaging(n=46,14.6%).Among 65 nodules subjected to gene(EGFR)mutation analyses,28(43.1%)cases(EGFR19 n=13;EGFR21 n=15)were identified as EGFR mutant and 37(56.9%)as EGFR *** to surgery,the majority of patients[n=194(83.6%)]received a contrast-enhanced CT scan for staging of both malignant[n=140(84.3%)]and benign[n=54(81.8%)]*** of positron emission tomography(PET)-CT was relatively uncommon[n=38(16.4%)].Conclusions:CT-derived nodule assessment assists in diagnosis of small to intermediate-sized malignant pulmonary ***,contrast-enhanced CT is commonly used as the sole diagnostic confirmation technique for pre-surgical staging,often resulting in surgery for late-stage disease and unnecessary surgery in cases of benign nodules.

关键词： Lung nodule diagnosis computed tomography pathology China

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Quantitative Trait Loci Analysis Identifies a Prominent Gene Involved in the Production of Fatty Acid-Derived Flavor Volatiles in Tomato

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Molecular Plant 2018年第9期11卷 1147-1165页

作者： Karolina Garbowicz Zhongyuan Liu Saleh Alseekh Denise Tieman Mark Taylor Anastasiya Kuhalskaya Itai Ofner Dani Zamir harry J. Klee Alisdair R. Fernie Yariv Brotman Max-Planck-lnstitute of Molecular Plant Physiology Potsdam-Golm Germany Horticultural Sciences Plant Innovation Center University of Florida Gainesville FL USA Center of Plant System Biology and Biotechnology 4000 Plovdiv Bulgaria Department of Life Sciences Ben-Gurion University of the Negev Beersheba Israel Robert H. Smith Institute of Plant Sciences and Genetics Faculty of Agriculture Hebrew University of Jerusalem Rehovot 7610001 Israel These authors contributed equally to this article

To gain insight into the genetic regulation of lipid metabolism in tomato, we conducted metabolic trait loci （mQTL） analysis following the lipidomic profiling of fruit pericarp and leaf tissue of the Solanum pennellii introgression lines （IL）. To enhance mapping resolution for selected fruit-specific mQTL, we profiled the lipids in a subset of independently derived S. pennellii backcross inbred lines, as well as in a nearsogenic sub-iL population. We identified a putative lecithin：cholesterol acyltransferase that controls the levels of several lipids, and two members of the class iii lipase family, LIP1 and LIP2, that were associated with decreased levels of diacylglycerols （DAGs） and triacylglycerols （TAGs）. Lipases of this class cleave fatty acids from the glycerol backbone of acylglycerols. The released fatty acids serve as precursors of flavor volatiles. We show that LIP1 expression correlates with fatty acid-derived volatile levels. We further confirm the function of LIP1 in TAG and DAG breakdown and volatile synthesis using transgenic plants. Taken together, our study extensively characterized the genetic architecture of Upophilic compounds in tomato and demonstrated at molecular level that release of free fatty acids from the glycerol backbone can have a major impact on downstream volatile synthesis.

关键词： lipidomics lipids lipase volatile FA-VOC Z-4-decenal

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