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Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

Acta Pharmaceutica Sinica B 2019年第5期9卷 997-1007页

作者： alexander j.trevarton Yan Zhou Dehua Yang Gordon W.Rewcastle jack U.Flanagan Antony Braithwaite Peter R.Shepherd Cristin G.Print Ming-Wei Wang Annette Lasham Department of Molecular Medicine and Pathology University of AucklandAucklandNew Zealand The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai201203China Auckland Cancer Society Research Centre AucklandNew Zealand Maurice Wilkins Centre for Molecular Biodiscovery University of AucklandAucklandNew Zealand Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Maurice Wilkins Centre for Molecular Biodiscovery University of OtagoDunedinNew Zealand School of Pharmacy Fudan UniversityShanghai201203China

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the E2 F1 promoter by YB-1. The second approach is a novel application of the Alpha Screen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

关键词： Cancer YB-1 Luciferase Alpha Screen Transcription factor Single-stranded DNA

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Assessment of the heartwood contribution to carbon accumulation in Pinus sylvestris L. trees under different forest site conditions

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FOREST ECOSYSTEMS 2025年第1期12卷 159-175页

作者： Galibina, Natalia A. Nikerova, Kseniya M. Moshnikov, Sergey A. Kryshen, alexander M. Russian Acad Sci Forest Res Inst Karelian Res Ctr 11 Pushkinskaya St Petrozavodsk 185910 Karelia Russia

Background: The heartwood (HW) proportion in the trunk of mature trees is an important characteristic not only for wood quality but also for assessing the role of forests in carbon sequestration. We have for the first time studied the proportion of HW in the trunk and the distribution of carbon and extractives in sapwood (SW) and HW of 70-80 year old Pinus sylvestris L. trees under different growing conditions in the pine forests of North-West Russia. Method: We have examined the influence of conditions and tree position in stand (dominant, intermediate and suppressed trees) in the ecological series: blueberry pine forest (Blu) - lingonberry pine forest (Lin) - lichen pine forest (Lic). We have analyzed the influence of climate conditions in the biogeographical series of Lin: the middle taiga subzone - the northern taiga subzone - the transition area of the northern taiga subzone and tundra. Results: We found that the carbon concentration in HW was 1.6%-3.4% higher than in SW, and the difference depended on growing conditions. Carbon concentration in HW increased with a decrease in stand productivity (Blu-Lin-Lic). In medium-productive stands, the carbon concentration in SW was higher in intermediate and supressed trees compared to dominant trees. In the series from south to north, carbon concentration in HW increased by up to 2%, while in SW, it rose by 2.7%-3.8%. Conclusions: Our results once again emphasized the need for an empirical assessment of the accurate carbon content in aboveground wood biomass, including various forest growing conditions, to better understand the role of boreal forests in carbon storage.

关键词： Scots pine Blueberry pine forest Lingonberry pine forest Lichen pine forest Tree social class Climate Carbon content Extractives Cellulose Lignin

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Lamotrigine-induced hemophagocytic lymphohistiocytosis associated with takotsubo cardiomyopathy, renal failure, encephalitis, and hemorrhagic shock

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World journal of Emergency Medicine 2025年第1期16卷 88-90页

作者： Ariella Gartenberg juan Esteban Munoz Eusse alexander Petrie Tsui Yuen Department of Emergency Medicine Jacobi Medical Center and Montefi ore Medical CenterBronx 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalBronx 10461USA

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and often fatal overactivation of the immune system. It is characterized by inappropriate and dysregulated activation of natural killer (NK) cells, CD8^(+)cytotoxic T cells, and macrophages. Ineffective interactions between NK cells, CD8^(+)T cells, and their pathogenic targets lead to massive cytokine accumulation and widespread macrophage activation. Resultant hemophagocytosis and excessive organdamaging infl ammation subsequently *** may be triggered by genetic or sporadic disorders,as well as specific events that alter immune *** events include inflammatory or infectious disease processes and malignancy.

关键词： histiocytosis phagocytic homeostasis

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Heterogeneous occurrence of evergreen broad-leaved forests in East Asia:Evidence from plant fossils

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Plant Diversity 2025年第1期47卷 1-12页

作者： jiagang Zhao Shufeng Li jian Huang Wenna Ding Mengxiao Wu Tao Su alexander Farnsworth Paul j.Valdes Linlin Chen Yaowu Xing Zhekun Zhou CAS Key Laboratory of Tropical Forest Ecology Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMengla 666303China University of Chinese Academy of Sciences Beijing 100049China Swiss Federal Institute for Forest Snow and Landscape Research WSL8903 BirmensdorfSwitzerland Senckenberg Natural History Collections Dresden Koonigsbrücker Landstraße 15901109 DresdenGermany State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation&Institute of Sedimentary Geology Chengdu University of TechnologyChengdu 610059China School of Geographical Sciences University of BristolBristol BS81SSUK State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China

Evergreen broad-leaved forests(EBLFs) are widely distributed in East Asia and play a vital role in ecosystem stability. The occurrence of these forests in East Asia has been a subject of debate across various disciplines. In this study, we explored the occurrence of East Asian EBLFs from a paleobotanical perspective. By collecting plant fossils from four regions in East Asia, we have established the evolutionary history of EBLFs. Through floral similarity analysis and paleoclimatic reconstruction, we have revealed a diverse spatio-temporal pattern for the occurrence of EBLFs in East Asia. The earliest occurrence of EBLFs in southern China can be traced back to the middle Eocene, followed by southwestern China during the late Eocene-early Oligocene. Subsequently, EBLFs emerged in japan during the early Oligocene and eventually appeared in central-eastern China around the Miocene. Paleoclimate simulation results suggest that the precipitation of wettest quarter(PWet Q, mm) exceeding 600 mm is crucial for the occurrence of EBLFs. Furthermore, the heterogeneous occurrence of EBLFs in East Asia is closely associated with the evolution of the Asian Monsoon. This study provides new insights into the occurrence of EBLFs in East Asia.

关键词： Evergreen broad-leaved forests(EBLFs) Plant fossils East Asia Paleoclimate Paleovegetation Asian monsoon

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Features of Thermocatalytic Cracking of Polypropylene in the Presence of Potassium Polytitanate and Zeolite Catalysts

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journal of Harbin Institute of Technology(New Series) 2025年第1期32卷 58-66页

作者： Nikita Zherdetsky alexander Gorokhovsky Roman Borisov Valentin Atlasov Department of Chemistry and Chemical Technology of Materials Yuri Gagarin Saratov State Technical UniversitySaratov 410054Russian Federation A.V.Topchiev Institute of Petrochemical Synthesis RAS Moscow 119991Russian Federation

A comparative study of products of thermal and thermocatalytic cracking of polypropylene(PP) in the presence of potassium polytitanate(PPT) synthesized by treatment of TiO_(2)(rutile) powder with molten mixture of KOH and KNO_(3) taken in a weight ratio of 30∶30∶40 has been carried *** was shown that the studied type of PPT powder exhibits catalytic properties in the reaction of thermal decomposition of PP,compared to the effect of commercial zeolite catalyst CBV-780 traditionally used for this *** on the analysis performed,the differences in the mechanism of catalytic action of PPT and the zeolite were *** reasons for the observed differences in the composition of PP cracking products and in the rate of coke formation on the surface of studied catalysts were *** the obtained results,it has been proposed that the CBV-780 catalyst promoted more intensive production of the gaseous hydrocarbons compared to PPT,due to higher specific surface area(internal surface) accessible for relatively light and small-sized hydrocarbon products of ***,intensive coke formation on the outer surface of the microporous zeolite contributes to the blocking of transport channels and the rapid loss of catalytic *** the same time,PPT,which initially has a smaller specific surface area,retains its catalytic activity significantly longer due to slit-shaped flat pores and higher transport accessibility of the inner surface.

关键词： polypropylene catalytic cracking potassium polytitanate zeolite reaction mechanism recycling

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Measuring user preferences and behaviour in a topographic immersive virtual environment(TopoIVE)of 2D and 3D urban topographic data

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International journal of Digital Earth 2021年第12期14卷 1835-1867页

作者： Łukasz Halik alexander j.Kent Department of Cartography and Geomatics Adam Mickiewicz UniversityPoznańPoland School of Psychology and Life Sciences Canterbury Christ Church UniversityCanterburyUK

This paper investigates user preferences and behaviour associated with 2D and 3D modes of urban representation within a novel Topographic Immersive Virtual Environment(TopoIVE)created from official 1:10,000 *** participants were divided into two groups:the first were given a navigational task within a simulated city and the second were given the freedom to explore it.A Head-Mounted Display(HMD)Virtual Reality(VR)app allowed participants to switch between 2D and 3D representations of buildings with a remote controller and their use of these modes during the experiment was *** performed mental rotation tests before entering the TopoIVE and were interviewed afterwards about their experiences using the *** results indicate that participants preferred the 3D mode of representation overall,although preference for the 2D mode was slightly higher amongst those undertaking the navigational task,and reveal that different wayfinding solutions were adopted by participants according to their ***,the findings suggest that users exploit different aspects of 2D and 3D modes of visualization in their wayfinding strategy,regardless of their *** potential to combine the functionality of 2D and 3D modes therefore offers substantial opportunities for the development of immersive virtual reality products derived from topographic datasets.

关键词： Virtual reality(VR) immersive virtual environment(IVE) 2D versus 3D wayfinding topographic data

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Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

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Cell Research 2005年第6期15卷 465-473页

作者： Francois MA PUjOL,alexander j KASTANIOTIS,j Kalervo HILTUNEN Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland

Genes encoding enzymes involved in biosynthesis of very long chain fatty acids were significantly up-regulatedduring early cotton fiber development. Two cDNAs, GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoAreductases that catalyze the second step in fatty acid elongation, were isolated from developing cotton fibers. GhKCR1and 2 contain open reading frames of 963 bp and 924 bp encoding proteins of 320 and 307 amino acid residues,respectively. Quantatitive RT-PCR analysis showed that both these genes were highly preferentially expressed duringthe cotton fiber elongation period with much lower levels recovered from roots, stems and leaves. GhKCR1 and 2showed 30%-32% identity to Saccharomyces cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAswere cloned and expressed in yeast haploid ybr159w? mutant that was deficient in 3-ketoacyl-CoA reductase ***-type growth rate was restored in ybr159w? cells that expressed either GhKCR1 or 2. Further analysis showed thatGhKCR1 and 2 were co-sedimented within the membranous pellet fraction after high-speed centrifugation, similar to theyeast endoplasmic reticulum marker ScKar2p. Both GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductaseactivity in an in vitro assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results suggest thatGhKCR1 and 2 are functional orthologues of ScYbr159p.

关键词： very-long-chain fatty acids endoplasmic reticulum fatty acid elongation system 3-ketoacyl-CoA reductase Gossypium hirsutum short-chain alcohol dehydrogenase/reductase protein family.

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Forces and energetics of intermittent swimming

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Acta Mechanica Sinica 2017年第4期33卷 725-732页

作者： Daniel Floryan Tyler Van Buren alexander j.Smits Department of Mechanical and Aerospace Engineering Princeton University Princeton NJ 08544 USA

Experiments are reported on intermittent swimming motions. Water tunnel experiments on a nominally two-dimensional pitching foil show that the mean thrust and power scale linearly with the duty cycle, from a value of 0.2 all the way up to continuous motions, indicating that individual bursts of activity in intermittent motions are independent of each other. This conclusion is corroborated by particle image velocimetry（PIV） flow visualizations, which show that the main vortical structures in the wake do not change with duty cycle. The experimental data also demonstrate that intermittent motions are generally energetically advantageous over continuous motions. When metabolic energy losses are taken into account, this conclusion is maintained for metabolic power fractions less than 1.

关键词： intermittent swimming maintained conclusion cycle thrust favorable producing aquatic circles

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Interaction of Radiation and Turbulent Natural Convection:A Pseudo-Direct Numerical Study

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Advances in Applied Mathematics and Mechanics 2022年第6期14卷 1567-1586页

作者： alexander Nee Ali j.Chamkha Research and Educational Center of I.N.Butakov National Research Tomsk Polytechnic UniversityTomskRussia Faculty of Engineering Kuwait College of Science and TechnologyDoha DistrictKuwait

This paper presents a hybrid lattice Boltzmann solver for turbulent buoyancy-driven flow coupled with surface thermal *** two-relaxation time scheme for the Boltzmann equation combined with the implicit finite difference scheme for the energy equation is implemented to compute the heat transfer and fluid flow *** accuracy and robustness of the hybrid approach proposed in this study are assessed in terms of the numerical and experimental data of other *** performing the simulation,the Rayleigh number is ranged from 108 to 1010 whereas the surface emissivity is changed from zero to *** computations,it is found that the overall temperature of the cavity is increased as a result of enhancing the surface *** plumes are formed both at the isothermal and the thermally-insulated walls with the Ra109 and#*** the conditions under study,the overall heat transfer rate is raised by around 5%when taking into account the surface thermal radiation.

关键词： Pseudo-direct numerical simulation surface radiation hybrid lattice Boltzmann scheme turbulent natural convection.

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