The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-s...The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411(HA-tagged Ssp411)mouse model.This model is instrumental in probing the expression and function of Ssp411.Our research revealed that Ssp411 is expressed in the round spermatids,elongating spermatids,elongated spermatids,and epididymal spermatozoa.The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis.Nevertheless,rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions.Ssp411 is not detectable in metaphase Ⅱ(MⅡ)oocytes,zygotes,or 2-cell stage embryos,highlighting its intricate role in early embryonic development.These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP,fostering groundbreaking advancements in the f ields of spermiogenesis and reproductive biology.展开更多
Utilizing small molecules as markers for specific cells or organs within biosystems is a crucial approach for studying and regulating physiological processes. However, current tagging strategies, due to the presence o...Utilizing small molecules as markers for specific cells or organs within biosystems is a crucial approach for studying and regulating physiological processes. However, current tagging strategies, due to the presence of exposed highly reactive groups, suffer from drawbacks such as low tagging efficiency or insufficient spatial specificity, thereby diminishing their expected effectiveness. Consequently, there is a pressing need to develop a strategy capable of in situ labeling of active groups in response to cellular or in vivo stimuli, ensuring both high tagging efficiency and spatial specificity. In this work, we devised a strategy for releasing aldehyde groups activated by hypochlorous acid(HOCl). Compounds synthesized through this strategy can release the fiuorophore methylene blue(MB) and aldehyde-based compounds upon HOCl activation. Given high reactivity of the released aldehyde group, it can effectively interact with macromolecules in biological systems, facilitating tagging and enabling prolonged imaging. To validate this concept, we further incorporated a naphthalimide structure with stable light emission to create SW-110. SW-110 can specifically respond to in vitro and endogenous HOCl, when release MB, it also releases naphthalimide fiuorophore with highly reactive aldehyde group for tagging within cells. This strategy provides a simple but efficient strategy for proximity tagging in situ.展开更多
Tag recommendation systems can significantly improve the accuracy of information retrieval by recommending relevant tag sets that align with user preferences and resource characteristics.However,metric learning method...Tag recommendation systems can significantly improve the accuracy of information retrieval by recommending relevant tag sets that align with user preferences and resource characteristics.However,metric learning methods often suffer from high sensitivity,leading to unstable recommendation results when facing adversarial samples generated through malicious user behavior.Adversarial training is considered to be an effective method for improving the robustness of tag recommendation systems and addressing adversarial samples.However,it still faces the challenge of overfitting.Although curriculum learning-based adversarial training somewhat mitigates this issue,challenges still exist,such as the lack of a quantitative standard for attack intensity and catastrophic forgetting.To address these challenges,we propose a Self-Paced Adversarial Metric Learning(SPAML)method.First,we employ a metric learning model to capture the deep distance relationships between normal samples.Then,we incorporate a self-paced adversarial training model,which dynamically adjusts the weights of adversarial samples,allowing the model to progressively learn from simpler to more complex adversarial samples.Finally,we jointly optimize the metric learning loss and self-paced adversarial training loss in an adversarial manner,enhancing the robustness and performance of tag recommendation tasks.Extensive experiments on the MovieLens and LastFm datasets demonstrate that SPAML achieves F1@3 and NDCG@3 scores of 22%and 32.7%on the MovieLens dataset,and 19.4%and 29%on the LastFm dataset,respectively,outperforming the most competitive baselines.Specifically,F1@3 improves by 4.7%and 6.8%,and NDCG@3 improves by 5.0%and 6.9%,respectively.展开更多
Influenza A viruses(IAVs)possess variable pathogenic potency causing great economic losses in the poultry industry worldwide and threatening public health.The control of IAV epidemics desperately necessitates an effic...Influenza A viruses(IAVs)possess variable pathogenic potency causing great economic losses in the poultry industry worldwide and threatening public health.The control of IAV epidemics desperately necessitates an efficient platform for screening antiviral compounds and evaluating vaccine efficacy.In this study,we utilized the H9N2 subtype IAV as the working model.An 11-amino-acid HiBiT tag,derived from NanoLuc luciferase,was incorporated into the flexible linker region of the NS1 protein.Subsequently,the recombinant HiBiT-tagged virus was rescued.The recombinant virus exhibited high genetic stability and similar virological characteristics to the parental virus,both in vitro and in vivo.Particularly importantly,the replication profile of the HiBiT-tagged virus can be easily measured using the Nano-Glo assay system,achieving an efficient screening platform.Based on this platform,we have developed assays with both convenience and efficiency for screening antiviral reagents,evaluating immunization efficacy,and measuring neutralizing antibodies.展开更多
In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF h...In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF hologram tensor exhibits a strong relationship between observation and spatial location,helping to improve the robustness to dynamic environments and equipment.Since RFID data is often marred by noise,we implement two types of deep neural network architectures to clean up the RF hologram tensor.Leveraging the spatial relationship between tags,the deep networks effectively mitigate fake peaks in the hologram tensors resulting from multipath propagation and phase wrapping.In contrast to fingerprinting-based localization systems that use deep networks as classifiers,our deep networks in the proposed framework treat the localization task as a regression problem preserving the ambiguity between fingerprints.We also present an intuitive peak finding algorithm to obtain estimated locations using the sanitized hologram tensors.The proposed framework is implemented using commodity RFID devices,and its superior performance is validated through extensive experiments.展开更多
【目的】基于猪极端饲料报酬表型,利用靶向切割标签技术(cleavage under targets and tagmentation,CUT&Tag)构建H3K27ac差异图谱,鉴定关联的启动子、增强子和关联候选基因,为猪饲料报酬解析提供基础数据。【方法】从209头杜洛克猪...【目的】基于猪极端饲料报酬表型,利用靶向切割标签技术(cleavage under targets and tagmentation,CUT&Tag)构建H3K27ac差异图谱,鉴定关联的启动子、增强子和关联候选基因,为猪饲料报酬解析提供基础数据。【方法】从209头杜洛克猪中筛选饲料报酬表型差异最大的4头个体分别组成低剩余采食量组(L组,n=2)和高剩余采食量组(H组,n=2)。利用CUT&Tag技术,以H3K27ac作为活性启动子和增强子的表观遗传标记对4头个体的肝脏组织进行全基因组扫描,鉴定关联启动子、增强子和候选基因,并进一步采用real-time quantitative PCR(RT-qPCR)对重要基因进行验证。【结果】共鉴定出47271个H3K27ac峰,包括15739个潜在启动子和31532个推定增强子,大部分的H3K27ac峰位于近端启动子区域。根据H3K27ac全基因的分布情况和作用特点,发现3087个差异峰(对应2188个基因),其中867个H3K27ac峰(对应664个基因)富集在H组,2220个H3K27ac峰(对应1575个基因)富集在L组。GO和KEGG结果发现H3K27ac增强子可能是通过影响胆汁酸代谢、淋巴细胞代谢和NF-κB通路来调节饲料报酬。RT-qPCR结果显示,与H组相比,DIAPH3、DPYD、FTO、TCF7L2、ABCC2、ABCC11、RXRA和ABCG8在L组中显著上调(P<0.05),而PAX5、GRHPR、NFATC1、CARD11、BLNK和LYN在L组中显著下调(P<0.05)。【结论】本研究成功生成了具有极端RFI差异的杜洛克猪肝脏组织中的H3K27ac差异图谱以及相关数据。基于该图谱鉴定和验证了关联候选基因,为进一步解析启动子和增强子调控饲料报酬的分子机制提供了基础数据。展开更多
This paper presents a low voltage, low power RF/analog front-end circuit for passive ultra high frequency （UHF） radio frequency identification （RFID） tags. Temperature compensation is achieved by a reference gener...This paper presents a low voltage, low power RF/analog front-end circuit for passive ultra high frequency （UHF） radio frequency identification （RFID） tags. Temperature compensation is achieved by a reference generator using sub-threshold techniques. The chip maintains a steady system clock in a temperature range from - 40 to 100℃. Some novel building blocks are developed to save system power consumption,including a zero static current power-on reset circuit and a voltage regulator. The RF/analog front-end circuit is implemented with digital base-band and EEPROM to construct a whole tag chip in 0. 18μm CMOS EEPROM technology without Schottcky diodes. Measured results show that the chip has a minimum supply voltage requirement of 0.75V. At this voltage, the total current consumption of the RF/analog frontend circuit is 4.6μA.展开更多
基金the support from the National Natural Science Foundation of China(No.32070849)The Foundation of Science and Technology Commission of Shanghai Municipality(No.22DX1900400)+1 种基金Science and Technology Commission of Shanghai Municipality(No.23JC1403803)Shanghai Municipal Science and Technology Commission Targeted Funding Project(No.22DX1900400).
文摘The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411(HA-tagged Ssp411)mouse model.This model is instrumental in probing the expression and function of Ssp411.Our research revealed that Ssp411 is expressed in the round spermatids,elongating spermatids,elongated spermatids,and epididymal spermatozoa.The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis.Nevertheless,rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions.Ssp411 is not detectable in metaphase Ⅱ(MⅡ)oocytes,zygotes,or 2-cell stage embryos,highlighting its intricate role in early embryonic development.These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP,fostering groundbreaking advancements in the f ields of spermiogenesis and reproductive biology.
基金financially supported by the National Natural Science Foundation of China (Nos. 22177019, 22377010, 22371038)State Key Laboratory for Modification of Chemical Fibers and Polymer Materials (No. KF2206)。
文摘Utilizing small molecules as markers for specific cells or organs within biosystems is a crucial approach for studying and regulating physiological processes. However, current tagging strategies, due to the presence of exposed highly reactive groups, suffer from drawbacks such as low tagging efficiency or insufficient spatial specificity, thereby diminishing their expected effectiveness. Consequently, there is a pressing need to develop a strategy capable of in situ labeling of active groups in response to cellular or in vivo stimuli, ensuring both high tagging efficiency and spatial specificity. In this work, we devised a strategy for releasing aldehyde groups activated by hypochlorous acid(HOCl). Compounds synthesized through this strategy can release the fiuorophore methylene blue(MB) and aldehyde-based compounds upon HOCl activation. Given high reactivity of the released aldehyde group, it can effectively interact with macromolecules in biological systems, facilitating tagging and enabling prolonged imaging. To validate this concept, we further incorporated a naphthalimide structure with stable light emission to create SW-110. SW-110 can specifically respond to in vitro and endogenous HOCl, when release MB, it also releases naphthalimide fiuorophore with highly reactive aldehyde group for tagging within cells. This strategy provides a simple but efficient strategy for proximity tagging in situ.
基金supported by the Key Research and Development Program of Zhejiang Province(No.2024C01071)the Natural Science Foundation of Zhejiang Province(No.LQ15F030006).
文摘Tag recommendation systems can significantly improve the accuracy of information retrieval by recommending relevant tag sets that align with user preferences and resource characteristics.However,metric learning methods often suffer from high sensitivity,leading to unstable recommendation results when facing adversarial samples generated through malicious user behavior.Adversarial training is considered to be an effective method for improving the robustness of tag recommendation systems and addressing adversarial samples.However,it still faces the challenge of overfitting.Although curriculum learning-based adversarial training somewhat mitigates this issue,challenges still exist,such as the lack of a quantitative standard for attack intensity and catastrophic forgetting.To address these challenges,we propose a Self-Paced Adversarial Metric Learning(SPAML)method.First,we employ a metric learning model to capture the deep distance relationships between normal samples.Then,we incorporate a self-paced adversarial training model,which dynamically adjusts the weights of adversarial samples,allowing the model to progressively learn from simpler to more complex adversarial samples.Finally,we jointly optimize the metric learning loss and self-paced adversarial training loss in an adversarial manner,enhancing the robustness and performance of tag recommendation tasks.Extensive experiments on the MovieLens and LastFm datasets demonstrate that SPAML achieves F1@3 and NDCG@3 scores of 22%and 32.7%on the MovieLens dataset,and 19.4%and 29%on the LastFm dataset,respectively,outperforming the most competitive baselines.Specifically,F1@3 improves by 4.7%and 6.8%,and NDCG@3 improves by 5.0%and 6.9%,respectively.
基金the Animal Ethics Committee of the Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences(SYXK-2020-0010).
文摘Influenza A viruses(IAVs)possess variable pathogenic potency causing great economic losses in the poultry industry worldwide and threatening public health.The control of IAV epidemics desperately necessitates an efficient platform for screening antiviral compounds and evaluating vaccine efficacy.In this study,we utilized the H9N2 subtype IAV as the working model.An 11-amino-acid HiBiT tag,derived from NanoLuc luciferase,was incorporated into the flexible linker region of the NS1 protein.Subsequently,the recombinant HiBiT-tagged virus was rescued.The recombinant virus exhibited high genetic stability and similar virological characteristics to the parental virus,both in vitro and in vivo.Particularly importantly,the replication profile of the HiBiT-tagged virus can be easily measured using the Nano-Glo assay system,achieving an efficient screening platform.Based on this platform,we have developed assays with both convenience and efficiency for screening antiviral reagents,evaluating immunization efficacy,and measuring neutralizing antibodies.
基金supported in part by the U.S.National Science Foundation(NSF)under Grants ECCS-2245608 and ECCS-2245607。
文摘In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF hologram tensor exhibits a strong relationship between observation and spatial location,helping to improve the robustness to dynamic environments and equipment.Since RFID data is often marred by noise,we implement two types of deep neural network architectures to clean up the RF hologram tensor.Leveraging the spatial relationship between tags,the deep networks effectively mitigate fake peaks in the hologram tensors resulting from multipath propagation and phase wrapping.In contrast to fingerprinting-based localization systems that use deep networks as classifiers,our deep networks in the proposed framework treat the localization task as a regression problem preserving the ambiguity between fingerprints.We also present an intuitive peak finding algorithm to obtain estimated locations using the sanitized hologram tensors.The proposed framework is implemented using commodity RFID devices,and its superior performance is validated through extensive experiments.
文摘Cache是处理器重要的存储模块,对处理器性能提升有着至关重要的作用.空间环境中,保护Cache免受软错误影响已成为设计新一代高可靠微处理器日益严峻的挑战.设计一种针对Cache Tag单错及邻位双错的低开销容错方法.可以保证Cache访问、Cache行填充和Cache行回写不受单位错误和邻位双错的影响,与传统SEC-FastTag容错方法相比,Tag单位及邻位双错容错能力得到提高.通过扩展FastTag结构优化设计,降低SEC-DAEC编解码逻辑带来的面积、功耗以及性能方面的开销.以四路组相连写回Cache为目标系统,与传统SEC-DAEC容错方法相比,本文提出的方法面积开销降低8.47%,功耗开销降低37.7%,关键路径时延减小0.13 ns.
文摘【目的】基于猪极端饲料报酬表型,利用靶向切割标签技术(cleavage under targets and tagmentation,CUT&Tag)构建H3K27ac差异图谱,鉴定关联的启动子、增强子和关联候选基因,为猪饲料报酬解析提供基础数据。【方法】从209头杜洛克猪中筛选饲料报酬表型差异最大的4头个体分别组成低剩余采食量组(L组,n=2)和高剩余采食量组(H组,n=2)。利用CUT&Tag技术,以H3K27ac作为活性启动子和增强子的表观遗传标记对4头个体的肝脏组织进行全基因组扫描,鉴定关联启动子、增强子和候选基因,并进一步采用real-time quantitative PCR(RT-qPCR)对重要基因进行验证。【结果】共鉴定出47271个H3K27ac峰,包括15739个潜在启动子和31532个推定增强子,大部分的H3K27ac峰位于近端启动子区域。根据H3K27ac全基因的分布情况和作用特点,发现3087个差异峰(对应2188个基因),其中867个H3K27ac峰(对应664个基因)富集在H组,2220个H3K27ac峰(对应1575个基因)富集在L组。GO和KEGG结果发现H3K27ac增强子可能是通过影响胆汁酸代谢、淋巴细胞代谢和NF-κB通路来调节饲料报酬。RT-qPCR结果显示,与H组相比,DIAPH3、DPYD、FTO、TCF7L2、ABCC2、ABCC11、RXRA和ABCG8在L组中显著上调(P<0.05),而PAX5、GRHPR、NFATC1、CARD11、BLNK和LYN在L组中显著下调(P<0.05)。【结论】本研究成功生成了具有极端RFI差异的杜洛克猪肝脏组织中的H3K27ac差异图谱以及相关数据。基于该图谱鉴定和验证了关联候选基因,为进一步解析启动子和增强子调控饲料报酬的分子机制提供了基础数据。
文摘This paper presents a low voltage, low power RF/analog front-end circuit for passive ultra high frequency （UHF） radio frequency identification （RFID） tags. Temperature compensation is achieved by a reference generator using sub-threshold techniques. The chip maintains a steady system clock in a temperature range from - 40 to 100℃. Some novel building blocks are developed to save system power consumption,including a zero static current power-on reset circuit and a voltage regulator. The RF/analog front-end circuit is implemented with digital base-band and EEPROM to construct a whole tag chip in 0. 18μm CMOS EEPROM technology without Schottcky diodes. Measured results show that the chip has a minimum supply voltage requirement of 0.75V. At this voltage, the total current consumption of the RF/analog frontend circuit is 4.6μA.
