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Emily Dickinson:An Interrogator of Death and Immortality 被引量:1
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作者 陈晗凝 《海外英语》 2011年第11X期226-227,231,共3页
Emily Dickinson is widely regarded as one of American's premier poets of the nineteenth century.In both style and content,her verse was,"revolutionary" in her day.Owing to the deep exploration of death a... Emily Dickinson is widely regarded as one of American's premier poets of the nineteenth century.In both style and content,her verse was,"revolutionary" in her day.Owing to the deep exploration of death and immortality,Emily Dickinson has become a puzzle in literary.As show in her poems,Dickinson's spiritual journey led her from na?ve nature-mysticism through disappointment,to a sacramental approach to immortality afterlife and further discouragement,culminating in a mature attitude of faithful unknowing and even more interrogating the immortality.This paper will base on the theory of the death and immortality through common people's fear to death,the essence of death,the significance of death to show the poetess's whole life-childhood,love,life condition,spiritual contradiction,and mainly her skeptical concept of death and immortality. 展开更多
关键词 DEATH and IMMORTALITY whole life SPIRITUAL JOURNEY interrogator analysis and CRITICISM
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On-Chip Sub-Picometer Continuous Wavelength Fiber-Bragg-Grating Interrogator 被引量:2
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作者 Yuan ZHUANG Jun ZOU +4 位作者 Jiqiang ZHANG Lu ZHANG Jiahe ZHANG Leixin MENG Qing YANG 《Photonic Sensors》 SCIE EI CSCD 2024年第1期73-84,共12页
Miniaturized fiber-Bragg-grating(FBG)interrogators are of interest for applications in the areas where weight and size controlling is important,e.g.,airplanes and aerospace or in-situ monitoring.An ultra-compact high-... Miniaturized fiber-Bragg-grating(FBG)interrogators are of interest for applications in the areas where weight and size controlling is important,e.g.,airplanes and aerospace or in-situ monitoring.An ultra-compact high-precision on-chip interrogator is proposed based on a tailored arrayed waveguide grating(AWG)on a silicon-on-insulator(SOI)platform.The on-chip interrogator enables continuous wavelength interrogation from 1544 nm to 1568 nm with the wavelength accuracy of less than 1 pm[the root-mean-square error(RMSE)is 0.73 pm]over the whole wavelength range.The chip loss is less than 5 dB.The 1×16 AWG is optimized to achieve a large bandwidth and a low noise level at each channel,and the FBG reflection peaks can be detected by multiple output channels of the AWG.The fabricated AWG is utilized to interrogate FBG sensors through the center of gravity(CoG)algorithm.The validation of an on-chip FBG interrogator that works with sub-picometer wavelength accuracy in a broad wavelength range shows large potential for applications in miniaturized fiber optic sensing systems. 展开更多
关键词 Fiber optic sensing on-chip interrogator arrayed waveguide grating center of gravity
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Isotopic identification of special nuclear materials based on delayedγrays from photofission fragments
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作者 Mei-Zhi Wang Hao-Yang Lan +4 位作者 Di Wu Xin-Lu Xu Rui-Rui Xu Xue-Qing Yan Wen Luo 《Nuclear Science and Techniques》 2025年第9期129-138,共10页
The illicit trafficking of special nuclear materials(SNMs)poses a grave threat to global security and necessitates the development of effective nuclear material identification methods.This study investigated a method ... The illicit trafficking of special nuclear materials(SNMs)poses a grave threat to global security and necessitates the development of effective nuclear material identification methods.This study investigated a method to isotopically identify the SNMs,including^(233,235,238)U,^(239-242)Pu,and^(232)Th,based on the detection of delayedγ-rays from photofission fragments.The delayedγ-ray spectra resulting from the photofission of SNMs irradiated by a 14 MeVγbeam with a total of 10~9 were simulated using Geant4.Three high-yield fission fragments,namely^(138)Cs,^(89)Rb,and^(94)Y,were selected as candidate fragments for SNM identification.The yield ratios of these three fragments were calculated,and the results from the different SNMs were compared.The yield ratio of^(138)Cs/^(89)Rb was used to identify most SNMs,including^(233,235,238)U,^(242)Pu,and^(232)Th,with a confidence level above 95%.To identify^(239-241)Pu with the same confidence,a higher total number of 10^(11)γbeams is required.However,although the^(94)Y/^(89)Rb ratio is suitable for elementally identifying SNMs,isotopic identification is difficult.In addition,the count rate of the delayedγabove 3 MeV can be used to rapidly detect the presence of nuclear materials. 展开更多
关键词 Special nuclear material identifications PHOTOFISSION Active interrogation Yield ratio
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Enhanced measurement precision with continuous interrogation during dynamical decoupling
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作者 张军 杜鹏 +3 位作者 敬雷 徐鹏 尤力 张文献 《Chinese Physics B》 SCIE EI CAS CSCD 2024年第3期88-94,共7页
Dynamical decoupling(DD)is normally ineffective when applied to DC measurement.In its straightforward implementation,DD nulls out DC signal as well while suppressing noise.This work proposes a phase relay method that ... Dynamical decoupling(DD)is normally ineffective when applied to DC measurement.In its straightforward implementation,DD nulls out DC signal as well while suppressing noise.This work proposes a phase relay method that is capable of continuously interrogating the DC signal over many DD cycles.We illustrate its efficacy when applied to the measurement of a weak DC magnetic field with an atomic spinor Bose-Einstein condensate.Sensitivities approaching standard quantum limit or Heisenberg limit are potentially realizable for a coherent spin state or a squeezed spin state of 10000 atoms,respectively,while ambient laboratory level noise is suppressed by DD.Our work offers a practical approach to mitigate the limitations of DD to DC measurement and would find other applications for resorting coherence in quantum sensing and quantum information processing research. 展开更多
关键词 quantum sensing continuous interrogation quantum magnetometer dynamical decoupling Heisenberg limit
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Microwave interrogation cavity for the rubidium space cold atom clock 被引量:3
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作者 任伟 高源慈 +2 位作者 李唐 吕德胜 刘亮 《Chinese Physics B》 SCIE EI CAS CSCD 2016年第6期137-143,共7页
The performance of space cold atom clocks(SCACs) should be improved thanks to the microgravity environment in space.The microwave interrogation cavity is a key element in a SCAC.In this paper,we develop a microwave ... The performance of space cold atom clocks(SCACs) should be improved thanks to the microgravity environment in space.The microwave interrogation cavity is a key element in a SCAC.In this paper,we develop a microwave interrogation cavity especially for the rubidium SCAC.The interrogation cavity has two microwave interaction zones with a single feedin source,which is located at the center of the cavity for symmetric coupling excitation and to ensure that the two interaction zones are in phase.The interrogation cavity has a measured resonance frequency of 6.835056471 GHz with a loaded quality factor of nearly 4200,which shows good agreement with simulation results.We measure the Rabi frequency of the clock transition of the rubidium atom in each microwave interaction zone,and subsequently demonstrate that the distributions of the magnetic field in the two interaction zones are the same and meet all requirements of the rubidium SCAC. 展开更多
关键词 interrogation cavity microwave interaction PHASE quality factor
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Rapid interrogation of special nuclear materials by combining scattering and transmission nuclear resonance fluorescence spectroscopy 被引量:4
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作者 Hao-Yang Lan Tan Song +2 位作者 Jia-Lin Zhang Jian-Liang Zhou Wen Luo 《Nuclear Science and Techniques》 SCIE EI CAS CSCD 2021年第8期67-77,共11页
The smuggling of special nuclear materials(SNMs)across national borders is becoming a serious threat to nuclear nonproliferation.This paper presents a feasibility study on the rapid interrogation of concealed SNMs by ... The smuggling of special nuclear materials(SNMs)across national borders is becoming a serious threat to nuclear nonproliferation.This paper presents a feasibility study on the rapid interrogation of concealed SNMs by combining scattering and transmission nuclear resonance fluorescence(s NRF and t NRF)spectroscopy.In s NRF spectroscopy,SNMs such as^(235,238)U are excited by a wide-band photon beam of appropriate energy and exhibit unique NRF signatures.Monte Carlo simulations show that one-dimensional scans can realize isotopic identification of concealed^(235,238)U when the detector array used for interrogation has sufficiently high energy resolution.The simulated isotopic ratio^(235U/238)U is in good agreement with the theoretical value when the SNMs are enclosed in relatively thin iron.This interrogation is followed by t NRF spectroscopy using a narrow-band photon beam with the goal of obtaining tomographic images of the concealed SNMs.The reconstructed image clearly reveals the position of the isotope^(235)U inside an iron rod.It is shown that the interrogation time of s NRF and t NRF spectroscopy is one order of magnitude lower than that when only t NRF spectroscopy is used and results in a missed-detection rate of 10^(-3).The proposed method can also be applied for isotopic imaging of other SNMs such as^(239,240)Pu and^(237)Np. 展开更多
关键词 Special nuclear material Nondestructive interrogation Nuclear resonance fluorescence
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Wireless Strain Measurement Based on a Microstrip Patch Antenna 被引量:2
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作者 Song Guorong Sun Tingting +4 位作者 Lu Yan Yan Tianting Wang Xuedong He Cunfu Wu Bin 《Transactions of Nanjing University of Aeronautics and Astronautics》 EI CSCD 2017年第5期477-486,共10页
Wireless interrogation of a rectangular microstrip patch antenna for strain measurement is investigated by simulations.To analyze the antenna performance,a microstrip line-feeding patch antenna at 10 GHz is designed.A... Wireless interrogation of a rectangular microstrip patch antenna for strain measurement is investigated by simulations.To analyze the antenna performance,a microstrip line-feeding patch antenna at 10 GHz is designed.A patch antenna wirelessly fed by a horn is proposed to measure the strain.The direction information of strain detected by the patch antenna is also considered.The strain can be detected both in the width and length directions.It is shown that the strain can be measured wirelessly using a standard horn antenna.This kind of wireless strain-sensing technique offers significant potential for wireless structural health monitoring(SHM),especially for high-end equipment. 展开更多
关键词 strain measurement wireless interrogation microstrip patch antenna structural health monitoring(SHM)
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A Calibration Method Based on Linear InGaAs in Fiber Grating Sensors Interrogation System 被引量:1
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作者 TAO Jun ZHANG Xia 《Semiconductor Photonics and Technology》 CAS 2009年第1期16-20,共5页
In accordance with the characteristics of wavelength shift detection in fiber grating sensor interrogation system,the wavelength interrogation system which uses linear InGaAs as the spectrum receiver is proposed.Orien... In accordance with the characteristics of wavelength shift detection in fiber grating sensor interrogation system,the wavelength interrogation system which uses linear InGaAs as the spectrum receiver is proposed.Orientation of optic spectrum line affects the silt of volume phase grating and size of InGaAs photosensitive unit,thus the calibration method is needed.Based on an analysis of InGaAs imaging model,least square curve fitting method is proposed to detect spectrum wavelength and InGaAs photosensitive unit position.The experimental results show that the methods are effective and the demodulation system precision is improved. 展开更多
关键词 fiber grating sensor interrogation linear InGaAs spectrum wavelength least square curvefitting
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Interrogating a Fiber Bragg Grating Vibration Sensor by Narrow Line Width Light 被引量:5
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作者 Jun Chang Dian-Heng Huo Liang-Zhu Ma Xiao-Hui Liu Tong-Yu Liu Chang Wang 《Journal of Electronic Science and Technology of China》 2008年第4期486-488,共3页
A method to interrogate fiber Bragg grating vibration sensor by narrow line width light is demonstrated. The interrogation scheme takes advantage of the intensity modulation of narrow spectral bandwidth light, such as... A method to interrogate fiber Bragg grating vibration sensor by narrow line width light is demonstrated. The interrogation scheme takes advantage of the intensity modulation of narrow spectral bandwidth light, such as distributed feedback laser, when a reflection or transmission spectrum curve of an fiber Bragg grating (FBG) moves due to the strain which is applied on the sensor. The sensor's response to accelerating frequency and amplitude is measured by experiment. The factors which have impacts on the sensitivity of the interrogation system are also discussed. 展开更多
关键词 Fiber Bragg grating (FBG) interrogation fiber Bragg grating sensor optical fiber vibration sensor.
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Optoelectronic oscillator-based interrogation system for Michelson interferometric sensors
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作者 Ling Liu Xiaoyan Wu +3 位作者 Guodong Liu Tigang Ning Jian Xu Haidong You 《Chinese Physics B》 SCIE EI CAS CSCD 2022年第9期249-253,共5页
High-performance interrogation systems for optical fiber sensors are extensively required for environmental condition monitoring applications.In this article,we propose and demonstrate a Michelson interferometer(MI)in... High-performance interrogation systems for optical fiber sensors are extensively required for environmental condition monitoring applications.In this article,we propose and demonstrate a Michelson interferometer(MI)interrogation system based on an optoelectronic oscillator(OEO).The frequency of the OEO is related to the free spectral range(FSR)of the MI.Thus,when the FSR of the MI varies with a change in external physical factors,the frequency of the OEO shifts and can be used for interrogation.We demonstrate that the temperature sensitivity and interrogation resolution are 35.35 MHz/℃and 0.012℃,respectively.Such an OEO-based scheme enables wavelength-to-frequency mapping and promises a wide linear interrogation range,high resolution and high-speed interrogation. 展开更多
关键词 interrogation system optical fiber sensor optoelectronic oscillator
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The Usages of“Ji(几)”in Yulin Dialect
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作者 LIANG Qing 《Journal of Literature and Art Studies》 2019年第5期513-518,共6页
In Yulin dialect,there are three usages of“ji(几)”:interrogative pronouns,numerals,and degree adverbs.When used as an interrogative pronoun,it is generally used to inquire about the number and degree where the inqui... In Yulin dialect,there are three usages of“ji(几)”:interrogative pronouns,numerals,and degree adverbs.When used as an interrogative pronoun,it is generally used to inquire about the number and degree where the inquiry number is generally small,but the number can be large when it is used in asking about age.When used as a number,it can represent not only integers between one and ten,but also decimal part.When used as a degree adverb,there are rich syntactic formats such as“ji(几)+verb”,“ji(几)+adjective”,different formats indicating different meanings.Compared with Mandarin,the usage of Yulin dialect“ji(几)”is more diverse.We also analyze the use of“ji(几)”from a diachronic perspective and finally we propose that due to the reanalysis of the syntactic format and the change of semantics,the“ji(几)”is further grammaticalized from interrogative pronoun to degree adverb. 展开更多
关键词 Yulin DIALECT degree ADVERB interrogative PRONOUN numeral GRAMMATICALIZATION
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Academic Study of Religion in Universities, Southwest Nigeria: In Search of Social Identity/Relevance
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作者 Danoye Oguntola-Laguda 《History Research》 2013年第3期147-153,共7页
Social theorists have engaged religion as a social agent and submitted that it has the capacity to foster positive and negative changes in the society. Milton Yinger, Emile Durkheim, and Karl Marx lead the pack among ... Social theorists have engaged religion as a social agent and submitted that it has the capacity to foster positive and negative changes in the society. Milton Yinger, Emile Durkheim, and Karl Marx lead the pack among other sociologists. The need to therefore interrogate religion as an agent of social engineering cannot be overemphasized normatively and functionally. One of the implications of such engagement is that religion; study and practice need to respond to issues in the society. Basic challenges facing the Nigerian nation are issues of poverty, diseases, corruption, and illiteracy. However, in Nigerian universities, the situation posits that religion is studied with theological intentions based on the curriculum bequeathed by the missionaries that laid the foundation for the academic study of religion in Nigeria leading to exclusive and reductionist approaches to its study. There is also government policy that placed emphasis on science and management courses for development. The situation has led to reduction in students' enrolments for the study of religion in Nigerian universities. Therefore, this paper seeks explanations for the non-functional design(s) of the curriculum for the academic study of religion in universities, southwest of Nigeria. Descriptive and analytic methods were adopted in the study to pursue the thesis that the academic study of religion in Nigeria should be rebranded and repackaged to respond and interrogate social challenges/problems, such as the scourge of HIV/AIDS plaguing the society thereby recreating a new social identity and relevance for its study. 展开更多
关键词 social theorists academic study university social identity and relevance interrogate
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Tensioned Metastable Fluid Detectors in Nuclear Security for Active Interrogation of Special Nuclear Materials―Part B
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作者 Jeffrey A. Webster Rusi P. Taleyarkhan 《World Journal of Nuclear Science and Technology》 2011年第3期66-76,共11页
This paper (constituting Part B) addresses active interrogation for detecting Special Nuclear Materials (SN- Ms) and includes description of the transformational Tensioned Metastable Fluid Detector (TMFD) based method... This paper (constituting Part B) addresses active interrogation for detecting Special Nuclear Materials (SN- Ms) and includes description of the transformational Tensioned Metastable Fluid Detector (TMFD) based method for optimal monitoring. One of the greatest difficulties in detection of SNMs by active interrogation is the task of distinguishing between the probing particles and the secondary particles that indicate the presence of SNMs. The TMFD’s selective insensitivity and γ photon blindness features are advantageous for alleviating this problem. The working principle of the TMFD is discussed along with its applications for security. The experimental work to date involving detection of small quantities of uranium with conventional detectors is discussed along with results of fission neutron detection. Statistically significant detection was achieved within 5 minutes of counting to ascertain and measure conclusive evidence for the presence of a 55g sample of uranium containing 235U. Results of simulations of three active detection techniques utilizing a TMFD system are presented. The process for using the TMFD to discriminate active source particles using timing and energy are described. These simulations indicate that it should be possible to utilize the TMFD system for optimal neutron-based interrogation of SNMs. 展开更多
关键词 Tensioned METASTABLE FLUID DETECTOR ACTIVE INTERROGATION TMFD SNM Detection
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Directive Function of Cooperative Principle in Trial Language
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作者 TIAN Yiming 《International English Education Research》 2016年第2期77-79,共3页
This paper aims to study the embodiment and directive function of Cooperative Principle in trial process. By analyzing dialogues in the sample trial transcript, the author will find out the embodiment of Cooperative P... This paper aims to study the embodiment and directive function of Cooperative Principle in trial process. By analyzing dialogues in the sample trial transcript, the author will find out the embodiment of Cooperative Principle in trial language, and draw a conclusion that the Cooperative Principle is important to direct the judge to discriminate if the suspect is cooperative, which helps the interrogation succeed. 展开更多
关键词 Cooperative Principle trial language INTERROGATION
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The Cartography of Focus and Interrogative Projections inǸjò`-Kóo
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作者 Simeon Olaogun 《宏观语言学》 2022年第1期77-100,共24页
Researches on cartography have made universal predictions on the hierarchies of functional projections in language.Based on this assumption,the structural maps established by Rizzi(1997,2001b)for the left-peripheral e... Researches on cartography have made universal predictions on the hierarchies of functional projections in language.Based on this assumption,the structural maps established by Rizzi(1997,2001b)for the left-peripheral elements suggest very strongly that Interrogative dominates Focus.Nevertheless,a straight-jacket adoption of this proposed hierarchical order to account for these left-peripheral projections inǸjò`-Kóo would be counterintuitive.Therefore,leaning on empirical and theoretical evidence,the paper calls to question the universality of the cartographers’claim,and argues that the opposite of the view is true ofǸjò`-Kóo.The paper adopts fieldwork method for data elicitation and descriptive approach as well as minimalist program for analysis of data.Data used in this study were elicited from purposively selected native speakers based on language proficiency.Data were acquired with syntactic checklist and structured interviews,and were subjected to interlinear and qualitative analysis. 展开更多
关键词 CARTOGRAPHY functional projections left-peripheral elements focus and interrogative projections Ǹjò`-Kóo
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Research on the Path of Higher Education Teaching Reform from the Perspective of Big Data
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作者 Mengsheng Cai 《Journal of Contemporary Educational Research》 2023年第5期1-5,共5页
The advent of the digital age has pointed out the direction for the development of higher education.In this paper,the undergraduate course“Science of Interrogation”is taken as the research subject,the challenges of ... The advent of the digital age has pointed out the direction for the development of higher education.In this paper,the undergraduate course“Science of Interrogation”is taken as the research subject,the challenges of big data teaching reform in universities are analyzed systematically,and concrete measures,such as adhering to the concept of teaching reform under the condition of big data,establishing professional teaching teams,improving the curriculum construction level,emphasizing on being student-centered,and optimizing the reform of the curriculum evaluation system,are proposed to address these challenges. 展开更多
关键词 Big data Higher education Science of Interrogation Teaching reform
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A Case Report:Traditional Chinese Medicine for Curing Psychosomatic Tinnitus Symptoms
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作者 Yu Guo Jie Chen 《Psychosomatic Medicine Research》 2021年第3期157-164,共8页
Patients with tinnitus are associated with adverse psychological reactions to varying degrees.Psychological interventions are currently the primary treatment to help patients eliminate negative responses to tinnitus.T... Patients with tinnitus are associated with adverse psychological reactions to varying degrees.Psychological interventions are currently the primary treatment to help patients eliminate negative responses to tinnitus.Traditional Chinese medicine uses four diagnostic methods or consultations.Interrogation is one such method.Through consultation,doctors can analyze the causes of tinnitus in patients,collect an accurate description,and assess the severity of the condition.At the same time,when doctors ask about other symptoms in a guided manner,they help patients refocus their attention to the symptoms so that their perception of tinnitus is changed,the vicious circular thinking patterns are broken,and their quality of life improves.When the patient understands why the physician establishes a medical plan,they are willing to cooperate actively and participate in a constructive doctor-patient relationship.This article analyzes the clinical methods and techniques of diagnosing tinnitus patients from the vantage of psychosomatic medicine,which has particular significance for the clinical treatment of tinnitus. 展开更多
关键词 Psychosomatic Medicine TINNITUS TCM Interrogation Cognitive behavioral therapy
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句子成份前移概述
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作者 李玉杰 杨群才 《新乡学院学报(社会科学版)》 1996年第3期10-15,共6页
本文主要阐述英语句子结构变化的一些问题。在英语文章中或日常英语谈话中,作者或说话人把句子中的某一成份前移,从而形成句子部分倒装或全部倒装,以适应语法结构、修辞或句子安排的需要。本文就谓语、宾语、表语和状语前移现象逐一进... 本文主要阐述英语句子结构变化的一些问题。在英语文章中或日常英语谈话中,作者或说话人把句子中的某一成份前移,从而形成句子部分倒装或全部倒装,以适应语法结构、修辞或句子安排的需要。本文就谓语、宾语、表语和状语前移现象逐一进行阐述。有关定语后移现象另文立论。 展开更多
关键词 句子成份functions in a SENTENCE 移pre-position 语序word order 语法结构sentence structure 主语subject 谓语predicate 宾语object 表语Predicatire 定语attrabute 状语adverbial 倒装invertion 疑问句interrogative SENTENCE 感汉句exclamative SENTENCE 否定句negative SENTENCE 省略句illipticai SENTENCE 标准英语stand ard ENGLISH 正式文体formal type of writing 书面语written ENGLISH 助动词auxiliary VERB 强调emphasis.
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Improving accuracy through double acousto-optic modulators in photonics-assisted mmWave heterodyne interferometric sensing
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作者 Yiwen Lu Tong Yang +6 位作者 Qizhuang Cen Xinpeng Wang Chong Liu Feifei Yin Kun Xu Ming Li Yitang Dai 《Chinese Optics Letters》 2025年第7期161-166,共6页
The acousto-optic modulator(AOM)plays an important role in heterodyne interferometric sensing,and it is always regarded as an ideal optical frequency shifter.In this paper,we compare the effects of its residual zero-o... The acousto-optic modulator(AOM)plays an important role in heterodyne interferometric sensing,and it is always regarded as an ideal optical frequency shifter.In this paper,we compare the effects of its residual zero-order diffraction in different AOM configurations.The theory shows that using double AOMs can effectively solve the same frequency crosstalk problem caused by zero-order perturbation without worsening the noise floor.The interferometer employs a photonics-assisted mmWave composed of two comb lines from an electro-optical frequency comb as the optical source,which results in the laser frequency noise cancellation in the difference.Experimentally,a dither with a peak-to-peak value of 0.15 ps in the single AOM configuration can be effectively suppressed to below the noise floor through double AOMs,which shows the potential to achieve high sensing accuracy. 展开更多
关键词 fiber-optic interferometric sensing heterodyne interrogation residual zero-order diffraction sensing accuracy photonics-assisted mmWave
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Massively parallel interrogation of human functional variants modulating cancer immunosurveillance
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作者 Ying Liu Yongshuo Liu +9 位作者 Xuran Niu Ang Chen Yizhou Li Ying Yu Binrui Mo Zhiheng Liu Tao Xu Jie Cheng Zeguang Wu Wensheng Wei 《Signal Transduction and Targeted Therapy》 2025年第4期2422-2439,共18页
Anti-PD-1/PD-L1 immune checkpoint blockade(ICB)therapy has revolutionized clinical cancer treatment,while abnormal PD-L1 or HLA-l expression in patients can significantly impact the therapeutic efficacy.Somatic mutati... Anti-PD-1/PD-L1 immune checkpoint blockade(ICB)therapy has revolutionized clinical cancer treatment,while abnormal PD-L1 or HLA-l expression in patients can significantly impact the therapeutic efficacy.Somatic mutations in cancer cells that modulate these critical regulators are closely associated with tumor progression and ICB response.However,a systematic interpretation of cancer immune-related mutations is stll lacking.Here,we harnessed the ABEmax system to establish a large-scale sgRNA library encompassing approximately 820,000 sgRNAs that target all feasible serine/threonine/tyrosine residues across the human genome,which systematically unveiled thousands of novel mutations that decrease or augment PD-L1 or HLA-I expression.Beyond residues associated with phosphorylation events,our screens also identified functional mutations that affect mRNA or protein stability,DNA binding capacity,protein-protein interactions,and enzymatic catalytic activity,leading to either gene inactivation or activation.Notably,we uncovered certain mutations that concurrently modulate PD-L1 and HLA-I expression,represented by the clinically relevant mutation SETD2_Y1666.We demonstrated that this mutation induces consistent phenotypic effects across multiple cancer cell lines and enhances the efficacy of immunotherapy in different tumor models.Our findings provide an unprecedented resource of functional residues that regulate cancer immunosurveillance,offering valuable guidance for clinical diagnosis,ICB therapy,and the development of innovative drugs for cancer treatment. 展开更多
关键词 massively parallel interrogation sgRNA library PD-L1 expression anti PD-PD-L1 immune checkpoint blockade HLA-I expression abemax system human functional variants somatic mutations
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