Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of...Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.展开更多
Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poise...Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.展开更多
针对飞卫星姿态确定和控制系统(attitude determination and control system,ADCS)中,IGRF地磁场模型的计算复杂度高和存储空间量大的问题,设计了均匀采样和K曲率加权2种历表模型。首先,给出了均匀历表模型的软件流程、存储格式、轨道...针对飞卫星姿态确定和控制系统(attitude determination and control system,ADCS)中,IGRF地磁场模型的计算复杂度高和存储空间量大的问题,设计了均匀采样和K曲率加权2种历表模型。首先,给出了均匀历表模型的软件流程、存储格式、轨道推演方法;然后,采用U曲率计算方法求解地磁场数据的离散曲率,并提出了K曲率加权方法设计非均匀历表模型;最后,比较了均匀采样和非均匀方法对原曲线的拟合程度,以及在ADCS中应用结果的比较。最终设计了适用于飞卫星的80点基于K曲率加权的非均匀历表模型,仅需0.96 kB存储空间,证明在计算速度和存储空间等方面和现有技术相比具有较大优势。展开更多
In a millimeter-wave(mmWave)Massive multiple-input multiple-output(MIMO)systems,full-digital beamforming(i.e.,connecting each antenna with a specific radio-frequency(RF)chain)becomes inefficient due to the hardware co...In a millimeter-wave(mmWave)Massive multiple-input multiple-output(MIMO)systems,full-digital beamforming(i.e.,connecting each antenna with a specific radio-frequency(RF)chain)becomes inefficient due to the hardware cost and power consumption.Therefore,hybrid analog and digital transceiver where the number of RF chains are much smaller than that of the antennas has drawn great research interest.In this work,we investigate the use of low-resolution analog-to-digital converters(ADCs)in the uplink of multi-user hybrid and full-digital mmWave Massive MIMO systems.To be specific,we compare the performance of full-digital minimum mean square error(MMSE)and hybrid MMSE beamforming in both sum rates and energy efficiency.Accurate approximations of sum rates and energy efficiency are provided for both schemes,which captures the dominant factors.The analytical results show that full-digital beamforming outperforms hybrid beamforming in terms of sum rates and requires only a small portion(γ)of antennas used by hybrid beamforming to achieve the same sum rates.We given sufficient condition for full-digital beamforming to outperform hybrid beamforming in terms of energy efficiency.Moreover,an algorithm is proposed to search for the optimal ADC resolution bits.Numerical results demonstrate the correctness of the analysis.展开更多
A reconfigurable intelligent surface(RIS)aided massive multiple-input multiple-output(MIMO)system is considered,where the base station employs a large antenna array with low-cost and low-power 1-bit analog-to-digital ...A reconfigurable intelligent surface(RIS)aided massive multiple-input multiple-output(MIMO)system is considered,where the base station employs a large antenna array with low-cost and low-power 1-bit analog-to-digital converters(ADCs).To compensate for the per-formance loss caused by the coarse quantization,oversampling is applied at the receiver.The main challenge for the acquisition of cascaded channel state information in such a system is to handle the distortion caused by the 1-bit quantization and the sample correlation caused by oversampling.In this work,Bussgang decomposition is applied to deal with the coarse quantization,and a Markov chain is developed to char-acterize the banded structure of the oversampling filter.An approximate message-passing based algorithm is proposed for the estimation of the cascaded channels.Simulation results demonstrate that our proposed 1-bit systems with oversampling can approach the 2-bit systems in terms of the mean square error performance while the former consumes much less power at the receiver.展开更多
A domain extension algorithm to correct the comparator offsets of pipeline analog-to-digital converters (ADCs) is presented, in which the 1.5-bit/stage ADC quantify domain is extended from a three-domain to a five-dom...A domain extension algorithm to correct the comparator offsets of pipeline analog-to-digital converters (ADCs) is presented, in which the 1.5-bit/stage ADC quantify domain is extended from a three-domain to a five-domain. This algorithm is designed for high speed and low comparator accuracy application. The comparator offset correction ability is improved. This new approach also promises significant improvements to the spurious-free dynamic range (SFDR), the total harmonic distortion (THD), the signal-to-noise ratio (SNR) and the minor analog and digital circuit modifications. Behavioral simulation results are presented to demonstrate the effectiveness of the algorithm, in which all absolute values of comparator offsets are set to |3Vref/8|. SFDR, THD and SNR are improved, from 34.62-dB, 34.63-dB and 30.33-dB to 60.23-dB, 61.14-dB and 59.35-dB, respectively, for a 10-bit pipeline ADC.展开更多
The successive approximation register(SAR)is one of the most energy-efficient analog-to-digital converter(ADC)architecture for medium-resolution applications.However,its high energy efficiency quickly diminishes when ...The successive approximation register(SAR)is one of the most energy-efficient analog-to-digital converter(ADC)architecture for medium-resolution applications.However,its high energy efficiency quickly diminishes when the target resolution increases.This is because a SAR ADC suffers from several major error source,including the sampling kT/C noise,the comparator noise,and the DAC mismatch.These errors are increasing hard to address in high-resolution SAR ADCs.This paper reviews recent advances on error suppression techniques for SAR ADCs,including the sampling kT/C noise reduction,the noise-shaping(NS)SAR,and the mismatch error shaping(MES).These techniques aim to boost the resolution of SAR ADCs while maintaining their superior energy efficiency.展开更多
Objective: To compare image quality and apparent diffusion coefficients (ADC) of the normal pancreas parenchymas in breath-hold, respiratory-triggered and free-breathing diffusion weighted imaging (DWI) at 3.0-Tesla. ...Objective: To compare image quality and apparent diffusion coefficients (ADC) of the normal pancreas parenchymas in breath-hold, respiratory-triggered and free-breathing diffusion weighted imaging (DWI) at 3.0-Tesla. Methods: DWI of the pancreas was performed at 3.0-Tesla in 21 healthy volunteers with breath-hold, respiratory-triggered and free-breathing using b-values of 0 and 500 s/mm2. For all three sequences, two readers assigned an image quality score to images at b0 and b500, and two independent readers measured ADCs for the head, body and tail of pancreas. Image quality scores and ADCs of pancreas in the three DWIs were compared. Results: For b0, image quality scores was not significantly different among the three sequences (p = 0.103). For b500, image quality score was significantly lower in free-breathing DWI than breath-hold or respiratory-triggered DWI (p = 0.000), and not significantly different between breath-hold and respiratory-triggered DWI (p = 0.212). Mean ADCs differed significantly among the anatomical regions with the lowest values measured in the pancreatic tail both at breath-hold and respiratory-triggered DWIs whereas no significant difference was found at free-breathing DWI. Conclusion: Breath-hold or respiratory-triggered technique provided DW images of pancreas with acceptable quality at 3.0-Tesla. Breath-hold is the preferred DWI technique for ADC measurements of pancreas.展开更多
High-speed, high-accuracy data converters are attractive for use in most RF applications. Such converters allow direct conversion to occur between the digital baseband and the antenna. However, high speed and high acc...High-speed, high-accuracy data converters are attractive for use in most RF applications. Such converters allow direct conversion to occur between the digital baseband and the antenna. However, high speed and high accuracy make the analog components in a converter more complex, and this complexity causes more power to be dissipated than if a traditional approach were taken. A static calibration technique for flash analog-to-digital converters （ADCs） is discussed in this paper. The calibration is based onhistogram test methods, and equivalent errors in the flash ADC comparators are estimated in the digital domain without any significant changes being made to the ADC comparators. In the trimming process, reference voltages are adjusted to compensate for static errors. Behavioral-level simulations of a moderate-resolution 8-bit flash ADC show that, for typical errors, ADC performance is considerably improved by the proposed technique. As a result of calibration, the differential no.nlinearities （DNLs） are reduced on average from 4 LSB to 0.5 LSB, and the integral nonlinearities （INLs） are reduced on average from 4.2 LSB to 0.35 LSB. Implementation issues for this proposed technique are discussed in our subsequent paper, “A Histogram-Based Static-Error Correction Technique for Flash ADCs： Implementation Aspects. ”展开更多
文摘Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.
文摘Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.
文摘针对飞卫星姿态确定和控制系统(attitude determination and control system,ADCS)中,IGRF地磁场模型的计算复杂度高和存储空间量大的问题,设计了均匀采样和K曲率加权2种历表模型。首先,给出了均匀历表模型的软件流程、存储格式、轨道推演方法;然后,采用U曲率计算方法求解地磁场数据的离散曲率,并提出了K曲率加权方法设计非均匀历表模型;最后,比较了均匀采样和非均匀方法对原曲线的拟合程度,以及在ADCS中应用结果的比较。最终设计了适用于飞卫星的80点基于K曲率加权的非均匀历表模型,仅需0.96 kB存储空间,证明在计算速度和存储空间等方面和现有技术相比具有较大优势。
基金supported in part by the Key Research&Development Plan of Jiangsu Province(No.BE2018108)National Nature Science Foundation of China(Nos.61701198&61772243)+3 种基金Nature Science Foundation of Jiangsu Province(No.BK20170557)Nature Science Foundation for Higher Education Institutions of Jiangsu Province of China(No.17KJB510009)the open research fund of National Mobile Communications Research Laboratory,Southeast University(No.2018D13)Young Talent Project of Jiangsu University and Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX18_0742)
文摘In a millimeter-wave(mmWave)Massive multiple-input multiple-output(MIMO)systems,full-digital beamforming(i.e.,connecting each antenna with a specific radio-frequency(RF)chain)becomes inefficient due to the hardware cost and power consumption.Therefore,hybrid analog and digital transceiver where the number of RF chains are much smaller than that of the antennas has drawn great research interest.In this work,we investigate the use of low-resolution analog-to-digital converters(ADCs)in the uplink of multi-user hybrid and full-digital mmWave Massive MIMO systems.To be specific,we compare the performance of full-digital minimum mean square error(MMSE)and hybrid MMSE beamforming in both sum rates and energy efficiency.Accurate approximations of sum rates and energy efficiency are provided for both schemes,which captures the dominant factors.The analytical results show that full-digital beamforming outperforms hybrid beamforming in terms of sum rates and requires only a small portion(γ)of antennas used by hybrid beamforming to achieve the same sum rates.We given sufficient condition for full-digital beamforming to outperform hybrid beamforming in terms of energy efficiency.Moreover,an algorithm is proposed to search for the optimal ADC resolution bits.Numerical results demonstrate the correctness of the analysis.
文摘A reconfigurable intelligent surface(RIS)aided massive multiple-input multiple-output(MIMO)system is considered,where the base station employs a large antenna array with low-cost and low-power 1-bit analog-to-digital converters(ADCs).To compensate for the per-formance loss caused by the coarse quantization,oversampling is applied at the receiver.The main challenge for the acquisition of cascaded channel state information in such a system is to handle the distortion caused by the 1-bit quantization and the sample correlation caused by oversampling.In this work,Bussgang decomposition is applied to deal with the coarse quantization,and a Markov chain is developed to char-acterize the banded structure of the oversampling filter.An approximate message-passing based algorithm is proposed for the estimation of the cascaded channels.Simulation results demonstrate that our proposed 1-bit systems with oversampling can approach the 2-bit systems in terms of the mean square error performance while the former consumes much less power at the receiver.
文摘A domain extension algorithm to correct the comparator offsets of pipeline analog-to-digital converters (ADCs) is presented, in which the 1.5-bit/stage ADC quantify domain is extended from a three-domain to a five-domain. This algorithm is designed for high speed and low comparator accuracy application. The comparator offset correction ability is improved. This new approach also promises significant improvements to the spurious-free dynamic range (SFDR), the total harmonic distortion (THD), the signal-to-noise ratio (SNR) and the minor analog and digital circuit modifications. Behavioral simulation results are presented to demonstrate the effectiveness of the algorithm, in which all absolute values of comparator offsets are set to |3Vref/8|. SFDR, THD and SNR are improved, from 34.62-dB, 34.63-dB and 30.33-dB to 60.23-dB, 61.14-dB and 59.35-dB, respectively, for a 10-bit pipeline ADC.
基金supported by National Natural Science Foundation of China(No.61904094,No.61934009)China Postdoctoral Science Foundation(No.2020M670329)Beijing Innovation Center for Future Chips(ICFC).
文摘The successive approximation register(SAR)is one of the most energy-efficient analog-to-digital converter(ADC)architecture for medium-resolution applications.However,its high energy efficiency quickly diminishes when the target resolution increases.This is because a SAR ADC suffers from several major error source,including the sampling kT/C noise,the comparator noise,and the DAC mismatch.These errors are increasing hard to address in high-resolution SAR ADCs.This paper reviews recent advances on error suppression techniques for SAR ADCs,including the sampling kT/C noise reduction,the noise-shaping(NS)SAR,and the mismatch error shaping(MES).These techniques aim to boost the resolution of SAR ADCs while maintaining their superior energy efficiency.
文摘Objective: To compare image quality and apparent diffusion coefficients (ADC) of the normal pancreas parenchymas in breath-hold, respiratory-triggered and free-breathing diffusion weighted imaging (DWI) at 3.0-Tesla. Methods: DWI of the pancreas was performed at 3.0-Tesla in 21 healthy volunteers with breath-hold, respiratory-triggered and free-breathing using b-values of 0 and 500 s/mm2. For all three sequences, two readers assigned an image quality score to images at b0 and b500, and two independent readers measured ADCs for the head, body and tail of pancreas. Image quality scores and ADCs of pancreas in the three DWIs were compared. Results: For b0, image quality scores was not significantly different among the three sequences (p = 0.103). For b500, image quality score was significantly lower in free-breathing DWI than breath-hold or respiratory-triggered DWI (p = 0.000), and not significantly different between breath-hold and respiratory-triggered DWI (p = 0.212). Mean ADCs differed significantly among the anatomical regions with the lowest values measured in the pancreatic tail both at breath-hold and respiratory-triggered DWIs whereas no significant difference was found at free-breathing DWI. Conclusion: Breath-hold or respiratory-triggered technique provided DW images of pancreas with acceptable quality at 3.0-Tesla. Breath-hold is the preferred DWI technique for ADC measurements of pancreas.
文摘High-speed, high-accuracy data converters are attractive for use in most RF applications. Such converters allow direct conversion to occur between the digital baseband and the antenna. However, high speed and high accuracy make the analog components in a converter more complex, and this complexity causes more power to be dissipated than if a traditional approach were taken. A static calibration technique for flash analog-to-digital converters （ADCs） is discussed in this paper. The calibration is based onhistogram test methods, and equivalent errors in the flash ADC comparators are estimated in the digital domain without any significant changes being made to the ADC comparators. In the trimming process, reference voltages are adjusted to compensate for static errors. Behavioral-level simulations of a moderate-resolution 8-bit flash ADC show that, for typical errors, ADC performance is considerably improved by the proposed technique. As a result of calibration, the differential no.nlinearities （DNLs） are reduced on average from 4 LSB to 0.5 LSB, and the integral nonlinearities （INLs） are reduced on average from 4.2 LSB to 0.35 LSB. Implementation issues for this proposed technique are discussed in our subsequent paper, “A Histogram-Based Static-Error Correction Technique for Flash ADCs： Implementation Aspects. ”
