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

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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

Physics-based,data-driven approach for predicting natural ventilation of residential high-rise buildings

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Building Simulation 2022年第1期15卷 129-148页

作者： Vincent J.L.Gan Boyu Wang C.M.Chan A.u.Weerasuriya jack C.P.Cheng Department of Building School of Design and EnvironmentNational University of SingaporeSingapore117566 Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong Kong999077China

Natural ventilation is particularly important for residential high-rise buildings as it maintains indoor human comfort without incurring the energy demands that air-conditioning *** improve a building’s natural ventilation,it is essential to develop models to understand the relationship between wind flow characteristics and the building's *** more effort is still needed for developing such reliable,accurate,and computationally economical models instead of currently the most popular physics-based models such as computational fluid dynamics(CFD)*** paper,therefore,presents a novel model developed based on physics-based modelling and a data-driven approach to evaluate natural ventilation in residential high-rise *** model first uses CFD to simulate wind pressures on the exterior surfaces of a high-rise *** the surface pressures have been obtained,multizone modelling is used to predict the air change per hour(ACH)for different flats in various ***-driven prediction models are then developed using data from the simulation and deep neural networks that are based on mean absolute error,mean absolute percentage error,and a fusion algorithm *** data-driven models are used to predict the ACH of 25 *** results from multizone modelling and data-driven modelling are *** results imply a high accuracy of the data-driven prediction in comparison with physics-based *** fusion algorithm-based neural network performs best,achieving 96%accuracy,which is the highest of all models *** study contributes a more efficient and robust method for predicting wind-induced natural *** findings describe the relationship between building design(e.g.,plan layout),distribution of surface pressure,and the resulting ACH,which serve to improve the practical design of sustainable buildings.

关键词： computational fluid dynamics data-driven prediction machine learning multizone model natural ventilation residential building

Principles to Support Modular Software Construction

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Journal of Computer Science & Technology 2017年第1期32卷 3-10页

作者： jack B. Dennis Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge MA 02139 U.S.A.

The construction of large software systems is always achieved through assembly of independently written components -- program modules. For these software components to work together, they must share a common set of data types and principles for representing structured data such as arrays of values and files. This common set of tools for creating and operating on data objects is provided by the infrastructure of the computer system： the hardware, operating system and runtime code. Because the nature and properties of these tools are crucial for correct operation of software components and their inter-operation, it is essential to have a precise specification that may be used for verifying correctness of application software on one hand, and to verify correctness of system behavior on the other. We call such a specification a program execution model （PXM）. It is evident that the properties of the PXM implemented by a computer system can have serious impact on the ability of application programmers to practice modular software construction. This paper discusses the concept of program execution models and presents a set of principles that a PXM must satisfy to provide a sound basis for modular software construction. Because parallel program execution on computer systems with many processing units is an essential part of contemporary computing environments, the expression of parallelism and modular software construction using components involving parallel operations is included in this treatment. The conclusion is that it is possible to build computer systems that implement a PXM within which any parallel program may be used, unmodified, as a component for building more substantial parallel programs.

关键词： program execution model data flow model codelet abstract architecture parallel computing

The development of *** erosion prediction and modeling

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International Soil and Water Conservation Research 2013年第2期1卷 1-11页

作者： John M.Laflen Dennis C.flanagan lowa State u. uSDA-ARS National Soil Erosion Research Laboratory West LafayetteIN

Soil erosion prediction technology began over 70 years ago when Austin Zingg published a relationship between soil erosion(by water)and land slope and length,followed shortly by a relationship by Dwight Smith that expanded this equation to include conservation ***,it was nearly 20 years before this work's expansion resulted in the universal Soil Loss Equation(uSLE),perhaps the foremost achievement in soil erosion prediction in the last *** uSLE has increased in application and complexity,and its usefulness and limitations have led to the development of additional technologies and new science in soil erosion research and *** among these new technologies is the Water Erosion Prediction Project(WEPP)model,which has helped to overcome many of the shortcomings of the uSLE,and increased the scale over which erosion by water can be *** of application of erosion prediction include almost all land types:urban,rural,cropland,forests,rangeland,and construction *** applications of WEPP include prediction of radioactive material movement with soils at a superfund cleanup site,and near real-time daily estimation of soil erosion for the entire state of Iowa.

关键词： universal Soil Loss Equation Water Erosion Prediction Project Soil erosion Erosion prediction History of erosion prediction

Arsenic variability and groundwater age in three water supply wells in southeast New Hampshire

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Geoscience Frontiers 2019年第5期10卷 1669-1683页

作者： Joseph P.Levitt James R.Degnan Sarah M.flanagan Bryant C.Jurgens u.S.Geological Survey

Three wells in New Hampshire were sampled bimonthly over three years to evaluate the temporal variability of arsenic concentrations and groundwater *** samples had measurable concentrations of arsenic throughout the entire sampling period and concentrations in individual wells had a mean variation of more than 7 μg/*** time series data from this sampling effort showed that arsenic concentrations ranged from a median of 4 mg/L in a glacial aquifer well (SGW-65) to medians of 19 μg/L and 37 μg/L in wells (SGW-93 and KFW-87) screened in the bedrock aquifer,*** high arsenic concentrations were associated with the consistently high pH (median ≥- 8) and low dissolved oxygen (median uifer wells,which is typical of fractured crystalline bedrock aquifers in New *** from the glacial aquifer often has high dissolved oxygen,but in this case was consistently *** pH also is generally acidic in the glacial aquifer but in this case was slightly alkaline (median =7.5).Also,sorption sites may be more abundant in glacial aquifer deposits than in fractured bedrock which may contribute to lower arsenic *** groundwater ages were less than 50 years old in all three wells and correlated with conservative tracer concentrations,such as chloride;however,mean age was not directly correlated with arsenic *** concentrations at KFW-87 did correlate with water levels,in addition,there was a seasonal pattern,which suggests that either the timing of or multiple sampling efforts may be important to define the full range of arsenic concentrations in domestic bedrock *** geochemically reduced conditions and alkaline pHs are common to both bedrock and glacial aquifer wells in this study,groundwater age correlates less strongly with arsenic concentrations than geochemical *** also is evidence of direct hydraulic connection between the glacial and bedrock aquifers,which can influe

关键词： Arsenic variability Geochemical time series Age tracers Groundwater age modeling

Reinforcement learning based dynamic distributed routing scheme for mega LEO satellite networks

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Chinese Journal of Aeronautics 2023年第2期36卷 284-291页

作者： Yixin HuANG Shufan Wu Zeyu KANG Zhongcheng Mu Hai HuANG Xiaofeng Wu Andrew jack TANG Xuebin CHENG School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai 200240China School of Astronautics Beihang UniversityBeijing 100191China School of Aerospace Mechanical and Mechatronic EngineeringThe University of SydneyCamperdown 2006Australia X-Laboratory The Second Academy of China Aerospace Science and Industry CorporationBeijing 100854China

Recently,mega Low Earth Orbit(LEO)Satellite Network(LSN)systems have gained more and more attention due to low latency,broadband communications and global coverage for ground *** of the primary challenges for LSN systems with inter-satellite links is the routing strategy calculation and maintenance,due to LSN constellation scale and dynamic network topology *** order to seek an efficient routing strategy,a Q-learning-based dynamic distributed Routing scheme for LSNs(QRLSN)is proposed in this *** achieve low end-toend delay and low network traffic overhead load in LSNs,QRLSN adopts a multi-objective optimization method to find the optimal next hop for forwarding data *** results demonstrate that the proposed scheme can effectively discover the initial routing strategy and provide long-term Quality of Service(QoS)optimization during the routing maintenance *** addition,comparison results demonstrate that QRLSN is superior to the virtual-topology-based shortest path routing algorithm.

关键词： LEO satellite networks Mega constellation Multi-objective optimization Routing algorithm Reinforcement learning

Hydrogen absorption properties of amorphous(Ni0.6Nb0.4-yTay)100-xZrx membranes

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Progress in Natural Science:Materials International 2017年第1期27卷 126-131页

作者： O.Palumbo F.Trequattrini N.Pal M.Hulyalkar S.Sarker D.Chandra T.flanagan M.Dolan A.Paolone CNR-ISC U.O.S. La Sapienza Department of Physics Sapienza University of Rome Department of Chemical and Materials Engineering University of Nevada Department of Chemistry University of Vermont CSIRO QCAT Energy 1 Technology CourtPullenvale

Ni based amorphous materials have great potential as hydrogen purification membranes. In the present work the melt spun(Ni0.6Nb0.4-yTay)100-xZrxwith y=0, 0.1 and x=20, 30 was studied. The result of X-ray diffraction spectra of the ribbons showed an amorphous nature of the alloys. Heating these ribbons below T us structure was retained. The crystallization process was characterized by differential thermal analysis and the activation energy of such process was obtained. The hydrogen absorption properties of the samples in their amorphous state were studied by the volumetric method,and the results showed that the addition of Ta did not significantly influence the absorption properties, a clear change of the hydrogen solubility was observed with the variation of the Zr content. The values of the hydrogenation enthalpy changed from37 k J/mol for x=30 to9k J/mol for x=20. The analysis of the volumetric data provides the indications about the hydrogen occupation sites during hydrogenation, suggesting that at the beginning of the absorption process the deepest energy levels are occupied, while only shallower energy levels are available at higher hydrogen content, with the available interstitial sites forming a continuum of energy levels.

关键词： Amorphous Ni based alloy ribbons High temperature X-ray diffraction DTA Activation energy Crystallization temperature Hydrogen solubility

MATHEMATICAL MODEL FOR THE ENTERPRISE COMPETITIVE ABILITY AND PERFORMANCE THROuGH A PARTICuLAR EMDEN-FOWLER EQuATION u〞-n^(-q-1)u(n)~q=0

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Acta Mathematica Scientia 2018年第4期38卷 1311-1321页

作者： Yue-Loong CHANC Meng-Rong LI C. jack YuE Yong-Shiuan LEE Tsung-Jui CHIANG-LIN Department of Phycology National Chengchi University Taipei China Department of Mathematical Sciences National Chengchi University Taipei China Department of Statisitics National Chengchi University Taipei China Graduate Institute of Finance National Taiwan University of Science and Technology Taipei China

In this article, we work with the ordinary equation u″-n-q-1u（n）q=0 and learn some interesting phenomena concerning the blow-up and the blow-up rate of solution to the equation.

关键词： estimate life-span blow-up blow-up rate competitive ability performance

Translational neuroscience and anxiety disorders

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中国神经精神疾病杂志 2006年第1期32卷 4-7页

作者： jack M. Gorman Department of Psychiatry the Mount Sinai School of Medicine One Gustave L. Levy Place Box 1230 New York NY U.S.A 暨南大学附属第一医院精神心理科

An approach to the study of psychiatric illnesses in which findings from basic a nd preclinical research are “translated” into clinically-relevant concepts tha t can then guide clinical research became possible in the late twentieth century . The explosion of knowledge from the basic neuroscience laboratory, improvements in techniques for studying the molecular biology of the brain, and the introduc tion of increasingly sophisticated neuroimaging technologies for human and anima l research all made translational research in psychiatry an exciting new possibi lity. At first glance, anxiety disorders would seem to be an excellent example o f a psychiatric disorder for the application of translational neuroscience appro aches because excellent animal models of fear exist and have been extensively ch aracterized. However, there is a great deal of controversy about the relationshi p between “fear” and “anxiety.” Many consider them to be separate concepts: fear represents an automatic response to a real danger whereas anxiety is a resp onse to indirect, exaggerated, or even imaged threats. If this notion is correct , then it is difficult to think of an animal having “anxiety” as opposed to fe ar and the translational approach becomes suspect.

关键词：神经科学焦虑症神经障碍医学研究

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