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301.
钟鸣
(2024-01-31 23:44):
#paper doi:10.1177/0146167218783195 The Cynical Genius Illusion: Exploring and Debunking Lay Beliefs About Cynicism and Competence
本文讨论的话题是“犬儒主义/愤世嫉俗/玩世不恭”,即那些精致利己、精明世俗、常持怀疑论且做预防性推理的人,与之对立的是非犬儒主义者/理想主义者,他们对陌生人的无私行为报以更少的动机揣度。通常,在艺术作品中愤世嫉俗者如福尔摩斯总被刻画成有能力、洞察力强、对环境的适应能力更强的人。为了确认“犬儒主义者是否拥有更强的能力(本文中泛指认知能力、学历、技能等具体技能)”,作者做了6个调查。前3个调查发现,世人的观念中,普遍认为犬儒主义者比非犬儒主义者能力更高,然而在后三个调查中,通过大规模的调查,作者发现真实情况与世人认识相反:非犬儒主义者的能力更强一些,绝大多数参与者预计愤世嫉俗的人在一系列认知任务和认知能力测试中比不愤世嫉俗的人表现得更好。作者分析认为,这可能是因为更高水平的教育和能力可能有助于个人首先发现并避免潜在的欺骗,从而减少负面社会经历的可能性,这反过来可能有助于对人性产生更积极的看法,此外,高水平的能力可能使个人能够正确识别其环境的“腐败”,并调整自己的愤世嫉俗程度以与之相匹配。最后,艺术作品中过于强调“愤世嫉俗的天才”也会强化公众的认知偏见。
Abstract:
Cynicism refers to a negative appraisal of human nature-a belief that self-interest is the ultimate motive guiding human behavior. We explored laypersons' beliefs about cynicism and competence and to what …
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Cynicism refers to a negative appraisal of human nature-a belief that self-interest is the ultimate motive guiding human behavior. We explored laypersons' beliefs about cynicism and competence and to what extent these beliefs correspond to reality. Four studies showed that laypeople tend to believe in cynical individuals' cognitive superiority. A further three studies based on the data of about 200,000 individuals from 30 countries debunked these lay beliefs as illusionary by revealing that cynical (vs. less cynical) individuals generally do worse on cognitive ability and academic competency tasks. Cross-cultural analyses showed that competent individuals held contingent attitudes and endorsed cynicism only if it was warranted in a given sociocultural environment. Less competent individuals embraced cynicism unconditionally, suggesting that-at low levels of competence-holding a cynical worldview might represent an adaptive default strategy to avoid the potential costs of falling prey to others' cunning.
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302.
小W
(2024-01-31 23:23):
#paper doi:doi.org/10.1038/s41586-023-06377-x A high-performance speech neuroprosthesis
本文介绍了脑机接口在将脑神经信号转化为文本语言的尝试。文章在患有延髓性肌萎缩侧索硬化症 (ALS)患者的大脑6v (entral premotor cortex)区域和44 (布洛卡区)使用四个微电极阵列检测神经活动信号,训练了一个循环神经网络 (RNN) 解码器,以在每 80 毫秒的时间步长预测当时说出每个音素的概率,将这些概率与语言模型相结合,神经活动信号以每分钟 62 个单词的速度被解码。在 50 个单词的数据集中实现了 9.1% 的单词错误率,125000 个单词的数据集的单词错误率为 23.8%。
同时布洛卡区作用在语言产生的高阶方面,但它似乎几乎不包含音素或单词的信息,即使在瘫痪多年后,患者仍存在音素发音的细节,说明仅从 6v 小区域检测的神经活动信号开发出以正常会话速度恢复瘫痪患者通信设备的可行性。
Abstract:
AbstractSpeech brain–computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although …
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AbstractSpeech brain–computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary1–7. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant—who can no longer speak intelligibly owing to amyotrophic lateral sclerosis—achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI2) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant’s attempted speech was decoded at 62 words per minute, which is 3.4 times as fast as the previous record8 and begins to approach the speed of natural conversation (160 words per minute9). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.
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303.
muton
(2024-01-31 23:04):
# paper:DOI: 10.1126/sciadv.abj4383 Emerged human-like facial expression representation in a deep convolutional neural network 最近的研究发现,经过训练以识别面部身份的深度卷积神经网络(DCNN)自发地学习了支持面部表情识别的特征,反之亦然。作者通过比较pretrain的VGG-Face,untrained VGG-Face以及VGG 16三个模型发现,只有pretrain的VGG-Face最后一层的1.25%的units表现出了和人类类似的面部表情识别以及表情混淆的特征。这些研究结果揭示了特定单元的面孔识别视觉经验对面孔表情知觉发展的必要性。
Abstract:
Recent studies found that the deep convolutional neural networks (DCNNs) trained to recognize facial identities spontaneously learned features that support facial expression recognition, and vice versa. Here, we showed that …
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Recent studies found that the deep convolutional neural networks (DCNNs) trained to recognize facial identities spontaneously learned features that support facial expression recognition, and vice versa. Here, we showed that the self-emerged expression-selective units in a VGG-Face trained for facial identification were tuned to distinct basic expressions and, importantly, exhibited hallmarks of human expression recognition (i.e., facial expression confusion and categorical perception). We then investigated whether the emergence of expression-selective units is attributed to either face-specific experience or domain-general processing by conducting the same analysis on a VGG-16 trained for object classification and an untrained VGG-Face without any visual experience, both having the identical architecture with the pretrained VGG-Face. Although similar expression-selective units were found in both DCNNs, they did not exhibit reliable human-like characteristics of facial expression perception. Together, these findings revealed the necessity of domain-specific visual experience of face identity for the development of facial expression perception, highlighting the contribution of nurture to form human-like facial expression perception.
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304.
白鸟
(2024-01-31 23:02):
#paper doi:10.1038/s41592-023-02117-1 SEVtras delineates small extracellular vesicles at droplet resolution from single-cell transcriptomes.因工作需要搜到这篇文献,
1.囊泡功能简介:胞外小囊泡(sEV)是由细胞分泌的微小囊泡,携带蛋白质、脂质和RNA等多种内容物,广泛存在于组织微环境中,充当细胞间信息交流的“信使”角色,生理病理过程中的关键参与者。
2.待解决:目前缺乏能够捕获到sEV复杂异质性和追踪sEV分泌的潜在细胞的高通量技术,需要证实检出的滴液为囊泡,
3.胞外小囊泡异质性追踪算法SEVtras:判定囊泡的算法,单细胞数据中追踪分泌囊泡的细胞来源;不同样本来源,广泛论证算法可行性;
从公共数据库中汇总胞外小囊泡关联基因集,利用最大期望算法(expectation–maximization, EM)推断单个液滴中胞外小囊泡的信号分值;
4.我的疑惑:对于细胞的身份和生物学功能研究是不容易的,囊泡的研究更甚,该算法可能需要更多的基准测试来证实;单细胞技术和囊泡是否适用;如何解析有限信息的囊泡表达谱?
问题1:判定捕获的barcode是不是为真实的囊泡--->通过SEVtras判别;
问题2:先暂不判定barcode身份(假定为真实的囊泡),基因表达谱可以分析出哪些内容?--->通过高表达基因的富集分析;
IF:36.100Q1
Nature methods,
2024-Feb.
DOI: 10.1038/s41592-023-02117-1
PMID: 38049696
PMCID:PMC10864178
Abstract:
Small extracellular vesicles (sEVs) are emerging as pivotal players in a wide range of physiological and pathological processes. However, a pressing challenge has been the lack of high-throughput techniques capable …
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Small extracellular vesicles (sEVs) are emerging as pivotal players in a wide range of physiological and pathological processes. However, a pressing challenge has been the lack of high-throughput techniques capable of unraveling the intricate heterogeneity of sEVs and decoding the underlying cellular behaviors governing sEV secretion. Here we leverage droplet-based single-cell RNA sequencing (scRNA-seq) and introduce an algorithm, SEVtras, to identify sEV-containing droplets and estimate the sEV secretion activity (ESAI) of individual cells. Through extensive validations on both simulated and real datasets, we demonstrate SEVtras' efficacy in capturing sEV-containing droplets and characterizing the secretion activity of specific cell types. By applying SEVtras to four tumor scRNA-seq datasets, we further illustrate that the ESAI can serve as a potent indicator of tumor progression, particularly in the early stages. With the increasing importance and availability of scRNA-seq datasets, SEVtras holds promise in offering valuable extracellular insights into the cell heterogeneity.
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305.
前进
(2024-01-31 22:50):
#paper arxiv.org//pdf/2311.026 2023 Exploring Grounding Potential of VQA-oriented GPT-4V for Zero-shot Anomaly Detection.
大型多模态模型 (LMM) GPT-4V(ision) 赋予 GPT-4 视觉grounding能力,使得通过视觉问答 (VQA) 范式处理某些任务成为可能。本文探讨了面向 VQA 的 GPT-4V 在最近流行的视觉异常检测(AD)中的潜力,并首次对流行的 MVTec AD 和 VisA 数据集进行定性和定量评估。 考虑到该任务需要图像/像素级评估,提出的 GPT-4V-AD 框架包含三个组成部分:1)粒度区域划分,2)提示设计,3)用于轻松定量评估的 Text2Segmentation,并做了一些不同的 尝试进行比较分析。 结果表明,GPT-4V可以通过VQA范式在零样本AD任务中取得一定的结果,例如在MVTec AD和VisA数据集上分别实现图像级77.1/88.0和像素级68.0/76.6 AU-ROC 。 然而,其性能与最先进的零样本方法(例如WinCLIP和CLIP-AD)相比仍然存在一定差距,需要进一步研究。 这项研究为零样本 AD 任务中面向 VQA 的 LMM 的研究提供了基线参考
arXiv,
2023.
DOI: 10.48550/arXiv.2311.02612
Abstract:
Large Multimodal Model (LMM) GPT-4V(ision) endows GPT-4 with visual groundingcapabilities, making it possible to handle certain tasks through the VisualQuestion Answering (VQA) paradigm. This paper explores the potential ofVQA-oriented GPT-4V …
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Large Multimodal Model (LMM) GPT-4V(ision) endows GPT-4 with visual groundingcapabilities, making it possible to handle certain tasks through the VisualQuestion Answering (VQA) paradigm. This paper explores the potential ofVQA-oriented GPT-4V in the recently popular visual Anomaly Detection (AD) andis the first to conduct qualitative and quantitative evaluations on the popularMVTec AD and VisA datasets. Considering that this task requires bothimage-/pixel-level evaluations, the proposed GPT-4V-AD framework contains threecomponents: 1) Granular Region Division, 2) Prompt Designing, 3)Text2Segmentation for easy quantitative evaluation, and have made somedifferent attempts for comparative analysis. The results show that GPT-4V canachieve certain results in the zero-shot AD task through a VQA paradigm, suchas achieving image-level 77.1/88.0 and pixel-level 68.0/76.6 AU-ROCs on MVTecAD and VisA datasets, respectively. However, its performance still has acertain gap compared to the state-of-the-art zero-shot method, e.g., WinCLIPann CLIP-AD, and further research is needed. This study provides a baselinereference for the research of VQA-oriented LMM in the zero-shot AD task, and wealso post several possible future works. Code is available at\url{https://github.com/zhangzjn/GPT-4V-AD}.
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306.
庞庞
(2024-01-31 21:42):
#paper doi:10.1001/jamapsychiatry 2023.5083 A Systematic Evaluation of Machine Learning-Based Biomarkers for Major Depressive 本文使用了四百万个机器学习模型,基于结构、功能、扩散磁共振成像探索了区分抑郁症患者和正常人的生物标记物。研究发现,通过多次优化,也很难找到可靠的生物标记物,说明了寻找抑郁症个体生物标记物的困难性,进一步阐明了对抑郁症进行分亚型的意义。
Abstract:
Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no …
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Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no informative biomarkers have been identified.Objective: To evaluate whether machine learning (ML) can identify a multivariate biomarker for MDD.Design, Setting, and Participants: This study used data from the Marburg-Münster Affective Disorders Cohort Study, a case-control clinical neuroimaging study. Patients with acute or lifetime MDD and healthy controls aged 18 to 65 years were recruited from primary care and the general population in Münster and Marburg, Germany, from September 11, 2014, to September 26, 2018. The Münster Neuroimaging Cohort (MNC) was used as an independent partial replication sample. Data were analyzed from April 2022 to June 2023.Exposure: Patients with MDD and healthy controls.Main Outcome and Measure: Diagnostic classification accuracy was quantified on an individual level using an extensive ML-based multivariate approach across a comprehensive range of neuroimaging modalities, including structural and functional magnetic resonance imaging and diffusion tensor imaging as well as a polygenic risk score for depression.Results: Of 1801 included participants, 1162 (64.5%) were female, and the mean (SD) age was 36.1 (13.1) years. There were a total of 856 patients with MDD (47.5%) and 945 healthy controls (52.5%). The MNC replication sample included 1198 individuals (362 with MDD [30.1%] and 836 healthy controls [69.9%]). Training and testing a total of 4 million ML models, mean (SD) accuracies for diagnostic classification ranged between 48.1% (3.6%) and 62.0% (4.8%). Integrating neuroimaging modalities and stratifying individuals based on age, sex, treatment, or remission status does not enhance model performance. Findings were replicated within study sites and also observed in structural magnetic resonance imaging within MNC. Under simulated conditions of perfect reliability, performance did not significantly improve. Analyzing model errors suggests that symptom severity could be a potential focus for identifying MDD subgroups.Conclusion and Relevance: Despite the improved predictive capability of multivariate compared with univariate neuroimaging markers, no informative individual-level MDD biomarker-even under extensive ML optimization in a large sample of diagnosed patients-could be identified.
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307.
符毓 Yu
(2024-01-31 21:30):
#paper doi:10.1049/elp2.12371 IET Power Electronics, 2023, AC losses calculation of parallel multi‐strand flat wire windings for automotive drive motor. 汽车驱动电机采用扁线绕组,提高了槽填充系数和效率。 然而,在当前驱动电机向高频化、高压化发展的环境下,绕组交流损耗的增加削弱了这些优势。交流损耗的准确分析和高性能绕组的设计已成为驱动电机设计过程中的关键问题和难点。基于绕组交流损耗产生机理,作者提出了一种绕组交流损耗分析方法,可以有效分离直流损耗、涡流损耗和环流损耗。该方法用于分析60 kW扁线绕线永磁同步电机(PMSM)的绕组交流损耗。此外,提出并联多股扁线绕组,以减少绕组交流损耗,消除电机磁负载对绕组层数选择的限制。计算了并联多股扁线绕组在不同频率下的交流损耗,这证明了所提出的绕组拓扑在降低绕组交流损耗方面的有效性。此外,通过实验验证了仿真模型的正确性,并通过有限元分析验证了损耗计算方法。
本文提出了一种准确分析绕组交流损耗的方法。基于该方法,计算了60kW永磁同步电机扁线绕组的交流损耗,并提出了一种可降低绕组交流损耗的高性能绕组结构。得到以下结论。
1)所提出的绕组交流损耗分析方法有效地分离了直流损耗、涡流损耗和环流损耗。该方法解决了绕组交流损耗成分分离的问题,可以考虑不同温度、频率、层数对绕组交流损耗的影响。为绕组交流损耗的研究提供了理论基础。
2)随着温度升高,绕组的直流损耗增大,而涡流损耗减小。另一方面,增加激励频率会导致涡流损耗和环流损耗增加。
3)增加绕组层数可以减少扁线绕组的涡流损耗。绕组中的涡流损耗始终在最接近槽口的导体中最大,约占总涡流损耗的60%。绕组EC损耗随着层数的增加而减小,8层绕组的涡流损耗比4层绕组降低了48.77%。
4) 绕组分成的股数越多,涡流损耗减少得越多,但产生的环流损耗也越多。通过采用端部绕组换位技术,可以有效抑制环流损耗,而涡流损耗的变化基本保持不变。所提出的并联多股扁线绕组在峰值速度下最大可降低26.28%的交流损耗,这证明所提出的绕组可以在不改变绕组层数的情况下有效地降低绕组交流损耗。
Abstract:
AbstractAutomobile drive motor with flat wire winding has improved the slot fill factor and efficiency. However, under the current environment of drive motors development to high frequency and voltage, the …
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AbstractAutomobile drive motor with flat wire winding has improved the slot fill factor and efficiency. However, under the current environment of drive motors development to high frequency and voltage, the increase in winding AC loss has weakened those advantages. Accurate analysis of AC loss and the design of high‐performance windings have become the key issues and difficulties in the design process of drive motors. Based on the winding AC loss generation mechanism, the authors propose a winding AC loss analysis method, which can effectively separate DC loss, eddy current loss, and circulating current loss. The method is used to analyse winding AC loss of 60 kW flat wire winding permanent magnet synchronous motor (PMSM). In addition, parallel multi‐strand flat wire windings are proposed to reduce the winding AC loss and eliminate the limitation of the magnetic load of the motor on the selection of winding layers. The AC loss of the parallel multi‐strand flat wire windings at different frequencies is calculated, which demonstrates the effectiveness of the proposed winding topology in reducing the winding AC loss. In addition, the correctness of the simulation model was verified through experiments, and the loss calculation method was verified through finite element analysis.
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308.
朵朵
(2024-01-31 20:18):
#paper
胡文涛,郭振雪.拜登政府修复美国国际声誉的外交叙事[J].现代国际关系,2023(11):104-118+155-156.
拜登政府如何讲好“美国故事”重塑美国形象。在特朗普政府时期美国优先政策极大损伤美国声誉后,拜登政府采取修复策略,试图重新建构美国的正面外交形象。《现代国际关系》刊文认为,拜登政府通过建立“美国回来了”的拟人化外交叙事,积极恢复与盟友关系,参与多边合作平台,一定程度上修复了国际社会对美国的印象,在一些重大或争议议题中巩固了盟友对美国的支持,改善了非盟友国家对美国国家形象的认知。然而,在实际事务处理上,美国体现出截然不同的利益判断和价值取向,无论是对多边机制的“选择性回归”,还是在经济问题上的“美国优先”本质,都在瓦解美国外交叙事的基础。
外交叙事是外交话语的一种特殊形式,要求外交实体从一国外交话语的特点和需求出发,用“故事化”的方式生动准确地宣传其外交理念和外交政策,实现与其他行为体的有效沟通和良性互动。美国非常注重形象政治,其历届政府都把建构和传播美国良好的国际形象作为重要使命,并将国际声誉等形象力量纳入国家软实力范畴。但在特朗普上台后,美国国际形象屡遭破坏,在特朗普任期结束前,许多传统盟友对美评价皆跌至历史最低点。为摆脱特朗普政府遗留下来的美国国际声誉负资产,拜登入主白宫后,其外交团队更是全面修正特朗普政府的外交叙事,力图尽快挽回和修复美国的国际声誉。
第一,拜登政府以“美国回来了”的拟人化外交叙事引领美国回归多边主义,重返国际社会,全力打造美国“合群遵约”的国际形象。在“美国优先”的导向下,特朗普政府的单边主义引发了包括其盟友在内的国际社会对美国严重不适。为扭转这一不利局面,拜登宣称“美国回来了”,以拟人化外交叙事重拾对多边主义及国际规则的重视。
拜登政府不仅明确表达了美国重返国际多边机制和国际社会的诉求,也在公开场合以显性或隐性叙事表现出对国际多边机制的遵从。2023年9月,拜登在第78届联合国大会上强调,美国作为一个负责任的大国将持续支持多边主义、人权、民主、自由等核心价值观。拜登政府以“美国回来了”的拟人化外交叙事取代和中止了特朗普政府在国际社会的单边主义论调,力图为美国塑造合群遵约的国际形象。
第二,拜登政府运用相对温和、正面的外交叙事积极修复与欧洲盟友的关系,为美国重返西方“民主同盟”的“盟主”宝座“清障”造势。特朗普在任期间,创造了跨大西洋关系的多个历史纪录:第一个公开表态“欧盟是一个敌人”的美国总统,第一个公开反对欧洲一体化的美国总统。特朗普政府“离经叛道”、偏激乖张的外交叙事使不少欧洲盟友对美国的国家信誉产生了严重质疑,从而导致其在西方世界的声誉不断下滑。
拜登上台后,为强化美欧关系纽带,美国支持“建立一个完整、自由与和平的欧洲,完全信守美国对北约盟国的承诺”。在对待欧洲盟友时,特朗普政府的外交叙事充斥负能量和否定性,拜登政府的外交叙事则相对温和、正面,因而更能引起欧洲盟友的共鸣,缓解或淡化盟友对美国的负面评价和敌对情绪。
第三,拜登政府重构美国参与全球气变治理的外交叙事,塑造美国参与全球气变治理的主导权和话语权,为修复美国国际声誉进行话语铺垫。当前,主要大国对全球气变治理的关注度、参与度以及其间的利益争夺都在升级。但是特朗普执政期间,美国在全球气变治理议题上采取全面倒退政策,致使全球气变治理陷入前所未有的僵局和困境,但也在一定程度上为拜登政府在全球气候变化治理议题上的大踏步前进预留了广阔空间。在多边层面,拜登政府努力提升和强化气候变化治理议题在外交战略上的重要性,给美国盟友和不少持观望态度的行为体打了“强心针”。
拜登执政团队汲取特朗普政府外交叙事重创美国国际声誉的教训,上台之初就着力采取修正举措,一定程度上改善了美国的国际形象。主要成效有三:
首先,拜登政府“美国回来了”拟人化外交叙事显示出平等的姿态,帮助美国在国际上缓解了一些不满和怨气。“美国回来了”以拟人化的叙事风格向外界宣示,美国要重回盟友“怀抱”,倾听盟友意见,重登“盟主”之位,重返国际社会大家庭,总体而言赢得了大多数国际行为体的理解和肯定。“美国回来了”的拟人化外交叙事显示出尊重、亲和的态度,在一定程度上恢复了其他行为体对美国“持久性特征和特性”的信任,有助于美国与各方良性互动。
其次,拜登政府相对温和、正面的外交叙事在一些重大或争议议题中帮助美国笼络住了盟友的支持。拜登政府相对温和、正面的外交叙事换来了欧洲不少盟友紧跟美国的回报。自2022年2月俄乌冲突爆发至今,有关西方国家对乌克兰的军事、财政和人道主义援助的研究表明,乌克兰的支持者首推美国,其次是波兰、英国、加拿大和德国。在全球性的公共议题上,拜登政府相对温和、正面的外交叙事使其在盟友中有所得分,收获了不少响应和支持。例如,美欧在参与全球气变治理的目标、原则、重点、路径等议题上存在明显的分歧和矛盾,但作为美国传统盟友的欧盟还是出台并实施了一些与美国步调比较一致的做法。
较之特朗普执政期间让美国盟友眼花缭乱、应接不暇的太多惊世骇俗之语和任性乖张做法,拜登政府的外交叙事相对温和正面,部分回归之前对于盟友“负责任、有担当”的“盟主”形象。
最后,拜登政府重构参与全球气变治理的外交叙事改变了非盟友国家对美国国家形象的认知,在一定程度上修复了美国国际声誉的基本面。特朗普执政期间坚持国家主义和孤立主义、坚持“美国优先”,引发美国与非盟友关系持续紧张而跌入低谷。以与东南亚关系为例,特朗普三次缺席东盟系列峰会,双边关系始终比较冷淡,美国在东南亚的声誉随之下降。拜登入主白宫后,多次强调东盟居于其“印太战略”的核心位置,同东盟加强气候变化合作是美国推进“印太战略”的重要内容。
目前,拜登政府已进入执政的“下半场”,而其通过外交叙事变革以修复美国国际声誉初见成效但未能持续。相比于执政初期的雄心壮志和动作频频,当下的拜登政府在修复美国国际声誉方面似乎呈现躺平的迹象,在拜登讲话或美国政府文件中越来越少见具体、专门的相关建议或措施。即便拜登政府(包括美国下一届政府)持续推动外交叙事“创新”,也未必能彻底扭转美国国际声誉总体不佳和缓慢下滑态势。特朗普政府以高调直白的“美国优先”“使美国再次伟大起来”的外交叙事将美国凌驾国际社会之上,而拜登政府则以委婉含蓄的“美国回来了”和诸多相对温和、正面的外交叙事包装其继续秉持的“美国优先”理念、维护美国霸权的战略意图,但终究难以获得其他行为体的信任。
国家的外交叙事具有能够向外部世界全面、精准地阐释国家外交理念和对外政策的重要优势,但外交叙事能否有效塑造、传播和维护国家国际声誉不仅仅取决于外交话语的内容、质量和议题选择,更取决于外交叙事主体是否能做到言行一致。拜登政府旨在修复和提升美国国际声誉的外交叙事变革与创新有得有失,值得深入思考。
309.
惊鸿
(2024-01-31 20:12):
#paper Pub Date : 2024-01-15
DOI : 10.1016/j.str.2023.12.012
tRNA 衍生片段 (tRF) 已成为免疫调节的关键参与者。一些RNase A 超家族成员参与 tRF 群体的形成。通过比较野生型和敲除型巨噬细胞系,我们之前的工作揭示了 RNase 2 可以选择性切割 tRNA。在这里,我们通过筛选合成 tRNA、单突变体和反密码子环 DNA/RNA 发夹来确认体外蛋白质切割模式。通过对 tRF 产物进行测序,我们确定了重组 RNase 2 的切割选择性,在 B 1 (U/C) 和 B 2 (A) 位点具有碱基特异性,这与之前的细胞研究一致。最后,通过MD模拟预测了蛋白质-发夹复合物。结果揭示了 α1、环 3 和环 4 以及 β6 RNase 2 区域的贡献,其中残基 Arg36/Asn39/Gln40/Asn65/Arg68/Arg132 提供相互作用,跨越对反密码子至关重要的P -1到 P 2位点循环识别。对 RNase 2 特异性 tRF 生成的了解可能会指导传染病和免疫相关疾病的新治疗方法。
Abstract:
tRNA-derived fragments (tRFs) have emerged as key players of immunoregulation. Some RNase A superfamily members participate in the shaping of the tRFs population. By comparing wild-type and knockout macrophage cell …
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tRNA-derived fragments (tRFs) have emerged as key players of immunoregulation. Some RNase A superfamily members participate in the shaping of the tRFs population. By comparing wild-type and knockout macrophage cell lines, our previous work revealed that RNase 2 can selectively cleave tRNAs. Here, we confirm the in vitro protein cleavage pattern by screening of synthetic tRNAs, single-mutant variants, and anticodon-loop DNA/RNA hairpins. By sequencing of tRF products, we identified the cleavage selectivity of recombinant RNase 2 with base specificity at B (U/C) and B (A) sites, consistent with a previous cellular study. Lastly, protein-hairpin complexes were predicted by MD simulations. Results reveal the contribution of the α1, loop 3 and loop 4, and β6 RNase 2 regions, where residues Arg36/Asn39/Gln40/Asn65/Arg68/Arg132 provide interactions, spanning from P to P sites that are essential for anticodon loop recognition. Knowledge of RNase 2-specific tRFs generation might guide new therapeutic approaches for infectious and immune-related diseases.
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310.
小年
(2024-01-31 19:56):
#paper Feng, Y., Xie, N., Inoue, F. et al. Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans. Nat Genet (2024). https://doi.org/10.1038/s41588-023-01626-1.
肤色是人类群体间一个显著的差异性状,具有高度遗传性的复杂性状,受到数百个基因位点的影响,其遗传基础尚未完全阐明。本篇文章作者采用了综合的功能基因组学分析方法,揭示了影响非洲人群肤色的遗传变异。该研究团队通过全基因组关联分析(GWAS)和自然选择扫描,鉴定了与肤色相关的单核苷酸多态性(SNP),利用大规模平行报告基因检测技术(MPRA),他们测试了这些SNP的调控活性。作者进一步使用 Hi-C 和 H3K27ac HiChIP 技术,构建了高分辨率的染色质相互作用图谱,以确定这些SNP的潜在靶基因。该研究通过荧光素酶报告基因检测、CRISPR基因编辑、转录组分析和黑色素丰度检测等技术,发现MITF 附近的 rs111969762、LEF1 附近的 rs17038630 和 TRPS1 附近的 rs11985280,这三个Di-SNP均能显著影响增强子活性及其靶基因的表达,可能对桑人皮肤色素的适应性进化发挥了作用。总得来说,本项研究发现了多个新的影响黑色素细胞中黑色素水平的新基因,这些发现有助于深入理解人类肤色的遗传机制,并为研究其他复杂性状的遗传因素提供了有价值的方法论。
IF:31.700Q1
Nature genetics,
2024-Feb.
DOI: 10.1038/s41588-023-01626-1
PMID: 38200130
PMCID:PMC11005318
Abstract:
Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. Here we applied massively parallel reporter assays to screen 1,157 candidate variants influencing skin …
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Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. Here we applied massively parallel reporter assays to screen 1,157 candidate variants influencing skin pigmentation in Africans and identified 165 single-nucleotide polymorphisms showing differential regulatory activities between alleles. We combine Hi-C, genome editing and melanin assays to identify regulatory elements for MFSD12, HMG20B, OCA2, MITF, LEF1, TRPS1, BLOC1S6 and CYB561A3 that impact melanin levels in vitro and modulate human skin color. We found that independent mutations in an OCA2 enhancer contribute to the evolution of human skin color diversity and detect signals of local adaptation at enhancers of MITF, LEF1 and TRPS1, which may contribute to the light skin color of Khoesan-speaking populations from Southern Africa. Additionally, we identified CYB561A3 as a novel pigmentation regulator that impacts genes involved in oxidative phosphorylation and melanogenesis. These results provide insights into the mechanisms underlying human skin color diversity and adaptive evolution.
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311.
盼盼
(2024-01-31 18:29):
https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29430本文应用浙江大学第二附属医院神经内科随访的亨廷顿病人信息,构建模型,经过分析发现患者血液中神经丝轻蛋白(Neurofilament light protein)可以预测Huntington's disease亨廷顿病人的发病年龄。这个蛋白主要跟发病年龄,发病前脑白质病变程度有关,但是跟发病之后的严重程度没有统计学关联。亨廷顿基因的串联重复序列数目越多,发病年龄也越早,而发病前重复序列数目多的患者,其NFL水平也比较高。总之,NFL可以作为预测亨廷顿病发病年龄的生物学marker,是本文解决的一个重要临床问题。
IF:7.400Q1
Movement disorders : official journal of the Movement Disorder Society,
2023-07.
DOI: 10.1002/mds.29430
PMID: 37148558
Abstract:
BACKGROUND: Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with …
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BACKGROUND: Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL.METHODS: Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained.RESULTS: Baseline samples were available from 110 controls, 90 premanifest HD (pre-HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre-HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre-HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset.CONCLUSIONS: Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.
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312.
Vincent
(2024-01-31 15:43):
#paper doi:https://www.jstor.org/stable/30047444 Journal of the American Statistical Association, 2006, Prediction by Supervised Principal Components. 当特征维度较高时,回归分析结果往往不是很理想,这一方面是因为数据噪声较大,另一方面是特征之间的相关性较高所导致的。这篇文章提出了一个简单有效的监督学习降维的框架,即根据特征与因变量之间的回归系数进行阈值筛选,再对筛出的少量特征降维,利用得到的主成分进行回归或者广义回归分析。这篇文章的主要理论贡献是在回归和生存分析的背景下论证了该方法的渐进一致性,比较了该方法其他方法(例如岭回归,lasso回归,偏最小二乘)的异同。文章最后还提到了该方法的局限性,例如无法处理单个特征与因变量边缘独立,但是几个特征联合起来与因变量不独立的情况等。
Abstract:
No abstract available.
313.
陆一幺
(2024-01-31 14:48):
#paper Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma, Cancer cell vol. 42,1 (2024): 135-156.e17. doi:10.1016/j.ccell.2023.11.010 本文利用基因组、转录组、单细胞转录组和空转,包括数字病理等多组学联合测序技术,对肝癌组织样本进行了转移机制的探索:1.肝癌瘤内异质性和进化轨迹:PT和MT病灶基因组层面比较类似(包括CNA层面),肝外转移主要是单中心谱系播种的,而非多中心模式,且来源比较多样化。多克隆播种方式预后会更差。2.低氧信号促进多克隆扩散:富含低氧信号的原发肿瘤被发现促进了多克隆扩散。3.新抗原异质性与T细胞反应性降低:转移肿瘤中观察到的显著肿瘤内新抗原异质性与T细胞反应性降低相关。可能是由于转移肿瘤细胞进化出了抗原递呈缺陷的能力。4.亚克隆选择机制:在亚克隆选择机制的研究中发现,没有Wnt突变的亚克隆显示出比有Wnt突变的亚克隆更强的转移选择性优势。此外,没有Wnt突变的转移肿瘤表现出更多的免疫抑制B细胞,这些B细胞通过HLA-E:CD94-NKG2A免疫检查点轴介导CD8+ T细胞的终末耗竭。 文章工作量非常大,但故事性非常好,值得精读。
Abstract:
Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in …
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Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitated polyclonal dissemination. Genomic divergence between primary and metastatic HCC is high, and early dissemination is prevalent. The remarkable neoantigen intratumor heterogeneity observed in metastases is associated with decreased T cell reactivity, resulting from disruptions to neoantigen presentation. We identify somatic copy number alterations as highly selected events driving metastasis. Subclones without Wnt mutations show a stronger selective advantage for metastasis than those with Wnt mutations and are characterized by a microenvironment rich in activated fibroblasts favoring a pro-metastatic phenotype. Finally, metastases without Wnt mutations exhibit higher enrichment of immunosuppressive B cells that mediate terminal exhaustion of CD8 T cells via HLA-E:CD94-NKG2A checkpoint axis. Collectively, our results provide a multi-dimensional dissection of the complex evolutionary process of metastasis.
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314.
哪有情可长
(2024-01-31 14:34):
#paper Cell-cycle-linked growth reprogramming encodes developmental time into leaf morphogenesis, Current Biology, 19 January 2024, https://doi.org/10.1016/j.cub.2023.12.050. 这篇文章开发出了针对植物活体组织生长的延时摄影体系,对拟南芥的幼小的叶片和成年叶片的发育进程从原基分化起始到形态分化进行全过程的追踪。该技术能够直观的展示植物年龄增长如何改变细胞的生长和增值,以及植物叶片内同等细胞层的组织形成潜力。后续为了验证这个体系的可靠性,选择了一个在拟南芥中前人鉴定发现的控制叶片的基因SPL9的突变体进行验证。本文的这个体系只能用于漏在外边的植物活体组织,但是像小麦穗和玉米穗这样前期被包裹的材料,进行活体组织生长的延时摄影应该还不能应用。
Abstract:
How is time encoded into organ growth and morphogenesis? We address this question by investigating heteroblasty, where leaf development and form are modified with progressing plant age. By combining morphometric …
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How is time encoded into organ growth and morphogenesis? We address this question by investigating heteroblasty, where leaf development and form are modified with progressing plant age. By combining morphometric analyses, fate-mapping through live-imaging, computational analyses, and genetics, we identify age-dependent changes in cell-cycle-associated growth and histogenesis that underpin leaf heteroblasty. We show that in juvenile leaves, cell proliferation competence is rapidly released in a "proliferation burst" coupled with fast growth, whereas in adult leaves, proliferative growth is sustained for longer and at a slower rate. These effects are mediated by the SPL9 transcription factor in response to inputs from both shoot age and individual leaf maturation along the proximodistal axis. SPL9 acts by activating CyclinD3 family genes, which are sufficient to bypass the requirement for SPL9 in the control of leaf shape and in heteroblastic reprogramming of cellular growth. In conclusion, we have identified a mechanism that bridges across cell, tissue, and whole-organism scales by linking cell-cycle-associated growth control to age-dependent changes in organ geometry.
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315.
半面阳光
(2024-01-31 13:17):
#paper DOI: https://doi.org/10.1002/pd.5079, Prenatal diagnosis, 2017, Comparing methods for fetal fraction determination and quality control of NIPT samples. 在无创产前筛查(NIPT)的分析流程中,胎儿游离DNA浓度(cell-free fetal DNA fraction )是一个重要的参数,尤其是检测样本中具有高背景浓度的母亲游离DNA(maternal cell-free DNA),计算fetal fraction是NIPT流程中的一个重要环节。这篇文献比较了四种计算fetal fraction的方法,分别是DEFRAG、BAYINDIR、SEQFF、SANEFALCON。作者手机了654例外周血样本,其中279例为女胎,375例为男胎,然后进行NGS测序,再分别用4种方法计算fetal fraction。研究结果发现,DEFRAG和BAYINDIR这两种基于Y染色体测序数据进行计算的方法一致性要优于另外两种可以同时计算男女胎fetal fraction的方法。其中DEFRAG在计算低胎儿浓度的样本时,表现比BAYINDIR方法更好。而SeqFF和SANEFALCON这两种可计算女胎胎儿浓度的方法,虽然不及DEFRAG和BAYINDIR的准确性,但是SANEFALCON在计算由于胎儿浓度低而分析失败样本时表现较好,甚至优于DEFRAG。此外,作者还探讨分析了孕妇BMI指数和孕周对计算fetal fraction的影响,结果显示DEFRAG在计算fetal fraction时受到这两个参数的影响较其他方法更明显。
Abstract:
OBJECTIVE: To compare available analysis methods for determining fetal fraction on single read next generation sequencing data. This is important as the performance of non-invasive prenatal testing (NIPT) procedures depends …
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OBJECTIVE: To compare available analysis methods for determining fetal fraction on single read next generation sequencing data. This is important as the performance of non-invasive prenatal testing (NIPT) procedures depends on the fraction of fetal DNA.METHODS: We tested six different methods for the detection of fetal fraction in NIPT samples. The same clinically obtained data were used for all methods, allowing us to assess the effect of fetal fraction on the test result, and to investigate the use of fetal fraction for quality control.RESULTS: We show that non-NIPT methods based on body mass index (BMI) and gestational age are unreliable predictors of fetal fraction, male pregnancy specific methods based on read counts on the Y chromosome perform consistently and the fetal sex-independent new methods SeqFF and SANEFALCON are less reliable but can be used to obtain a basic indication of fetal fraction in case of a female fetus.CONCLUSION: We recommend the use of a combination of methods to prevent the issue of reports on samples with insufficient fetal DNA; SANEFALCON to check for presence of fetal DNA, SeqFF for estimating the fetal fraction for a female pregnancy and any Y-based method for estimating the fetal fraction for a male pregnancy. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
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316.
尹志
(2024-01-31 10:39):
#paper doi: https://doi.org/10.48550/arXiv.2304.02643 Segment Anything。Meta在2023年的一篇工作,提出了一个CV领域的基础模型。文章的目标很清楚,通过prompt的方式,实现通用的segmentatoin任务。虽然在互联网上爆炒一轮后趋于平淡,但是对CV社区的影响还是非常大的。后续的Grounding-DINO,Grounded-SAM等工作,都有着不错的效果,而且对后续CV任务的解决给出了一套不同的思考范式。整个工作偏工程,或者想法上原创性的亮点不多,网络结构上也充分借鉴了大量基于Transformer的创新工作。值得一提的正是工程上的思路或者说解决方案。meta提出了一个新颖的任务,即:如何通过一个通用的任务来解决图像分割。进而设计训练流程和对应的损失。在过程中,设计了一套有效的数据标注引擎,实现了高效标注数据生产,这对于行业应用有着很强的借鉴价值。
从研究角度来看,如何充分利用预训练好的sam模型,大模型中的先验如何提取,从而为特定领域下游任务提供支持是一个重要的研究方向。
arXiv,
2023.
DOI: 10.48550/arXiv.2304.02643
Abstract:
We introduce the Segment Anything (SA) project: a new task, model, anddataset for image segmentation. Using our efficient model in a data collectionloop, we built the largest segmentation dataset to …
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We introduce the Segment Anything (SA) project: a new task, model, anddataset for image segmentation. Using our efficient model in a data collectionloop, we built the largest segmentation dataset to date (by far), with over 1billion masks on 11M licensed and privacy respecting images. The model isdesigned and trained to be promptable, so it can transfer zero-shot to newimage distributions and tasks. We evaluate its capabilities on numerous tasksand find that its zero-shot performance is impressive -- often competitive withor even superior to prior fully supervised results. We are releasing theSegment Anything Model (SAM) and corresponding dataset (SA-1B) of 1B masks and11M images at https://segment-anything.com to foster research into foundationmodels for computer vision.
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317.
徐炳祥
(2024-01-31 09:45):
#paper doi: 10.1038/s41588-020-00712-y Nature Genetics, 2020, CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction。本文介绍了一种基于计算机视觉中结构相似度(SSIM)的Hi-C数据相似度度量和结构变化区域的搜索算法,通过在基因组上进行滑窗计算,该算法不仅能基于Hi-C数据计算出两个样品在全基因组水平下染色质空间构象的相似程度,更能通过局部计算寻找出存在显著染色质空间构象变异的区域。该算法不仅可以进行同一物种内的比较,也可以进行跨物种比较。且对测序深度不敏感。本文将计算机视觉中的很多降噪/特征提取/形态学处理技术引入到了Hi-C相互作用图谱的处理中,对计算机上视觉技术在染色质空间构象数据的分析中的应用有重要参考价值。
Abstract:
Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes …
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Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data.
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318.
🐼太真实
(2024-01-30 21:45):
#paper: doi:2110.11316 文章《CLOOB: Modern Hopfield Networks with InfoLOOB Outperform CLIP》介绍了一种名为CLOOB(Contrastive Leave One Out Boost)的新型自监督学习方法。这种方法结合了现代霍普菲尔德网络(Modern Hopfield Networks)和InfoLOOB目标(Leave One Out Bound),用于提升对比学习的效能。CLOOB在零样本转移学习(zero-shot transfer learning)方面,不论在哪种架构或数据集上,均优于之前的CLIP方法。
CLOOB的核心是使用现代霍普菲尔德网络来增强数据的共现性和协方差结构。这种网络与传统的霍普菲尔德网络相比,具有更高的存储容量和更快的检索速度。通过使用这些网络,CLOOB能够加强输入样本中特征的共现性和协方差结构,有效地提取和强化数据中的重要特征。
此外,CLOOB还采用了InfoLOOB目标函数来避免InfoNCE目标函数中出现的饱和问题。InfoLOOB目标是一种对比学习的目标,用于处理匹配对和不匹配对之间的关系,以减少目标函数的饱和,并使得学习过程更加高效。
arXiv,
2021.
DOI: 10.48550/arXiv.2110.11316
CLOOB:带有 InfoLOOB 的现代 Hopfield 网络的性能优于 CLIP
Abstract:
CLIP yielded impressive results on zero-shot transfer learning tasks and isconsidered as a foundation model like BERT or GPT3. CLIP vision models thathave a rich representation are pre-trained using the …
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CLIP yielded impressive results on zero-shot transfer learning tasks and isconsidered as a foundation model like BERT or GPT3. CLIP vision models thathave a rich representation are pre-trained using the InfoNCE objective andnatural language supervision before they are fine-tuned on particular tasks.Though CLIP excels at zero-shot transfer learning, it suffers from anexplaining away problem, that is, it focuses on one or few features, whileneglecting other relevant features. This problem is caused by insufficientlyextracting the covariance structure in the original multi-modal data. Wesuggest to use modern Hopfield networks to tackle the problem of explainingaway. Their retrieved embeddings have an enriched covariance structure derivedfrom co-occurrences of features in the stored embeddings. However, modernHopfield networks increase the saturation effect of the InfoNCE objective whichhampers learning. We propose to use the InfoLOOB objective to mitigate thissaturation effect. We introduce the novel "Contrastive Leave One Out Boost"(CLOOB), which uses modern Hopfield networks for covariance enrichment togetherwith the InfoLOOB objective. In experiments we compare CLOOB to CLIP afterpre-training on the Conceptual Captions and the YFCC dataset with respect totheir zero-shot transfer learning performance on other datasets. CLOOBconsistently outperforms CLIP at zero-shot transfer learning across allconsidered architectures and datasets.
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319.
李翛然
(2024-01-30 16:22):
#paper: doi:doi.org/10.1186/s42825-019-0012-x Quantitative and structural analysis of isotopically labelled natural crosslinks in type I skin collagen using LC-HRMS and SANS 这篇文章主要介绍了使用液相色谱-高分辨质谱(LC-HRMS)和小角散射(SANS)技术对I型皮肤胶原蛋白中的同位素标记天然交联物进行定量和结构分析的方法和结果。这项研究对于了解皮肤胶原蛋白的结构和功能具有重要意义。
1. 样品制备:研究使用了同位素标记的I型皮肤胶原蛋白样品,通过特定的实验方法进行制备。
2. 液相色谱-高分辨质谱(LC-HRMS)分析:研究使用LC-HRMS技术对样品中的同位素标记天然交联物进行定量分析。LC-HRMS技术能够提供高分辨率和高灵敏度的分析结果。
3. 小角散射(SANS)分析:研究使用SANS技术对样品中的同位素标记天然交联物进行结构分析。SANS技术能够提供关于样品中交联物的大小、形状和分布等信息。
这篇论文的优势包括:
1. 综合分析方法:研究采用了LC-HRMS和SANS两种不同的分析技术,能够从定量和结构两个方面全面地研究同位素标记天然交联物。
2. 高分辨率和高灵敏度:LC-HRMS技术具有高分辨率和高灵敏度的特点,能够提供准确的定量分析结果。
3. 结构信息获取:SANS技术能够提供关于交联物的结构信息,有助于深入了解其在皮肤胶原蛋白中的分布和作用。
然而,这篇论文也存在一些局限性:
1. 样品限制:研究中使用的是同位素标记的I型皮肤胶原蛋白样品,可能无法完全代表自然状态下的胶原蛋白。
2. 技术限制:虽然LC-HRMS和SANS技术在分析同位素标记天然交联物方面具有优势,但仍然存在一定的局限性,如分析时间较长、设备成本较高等。
3. 结果解释:由于同位素标记天然交联物的复杂性,对于分析结果的解释可能存在一定的挑战,需要进一步的研究和验证。
总体而言,这篇论文通过综合应用LC-HRMS和SANS技术,提供了一种定量和结构分析同位素标记天然交联物的方法,并揭示了其在I型皮肤胶原蛋白中的特征和作用,为进一步研究皮肤胶原蛋白的结构和功能提供了重要的参考。 这文章证是我的研究方向,帮助很大
Abstract:
Abstract Collagen structure in biological tissues imparts its intrinsic physical properties by the formation of several covalent crosslinks. For the first time, two major crosslinks in the skin dihydroxylysinonorleucine (HLNL) …
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Abstract Collagen structure in biological tissues imparts its intrinsic physical properties by the formation of several covalent crosslinks. For the first time, two major crosslinks in the skin dihydroxylysinonorleucine (HLNL) and histidinohydroxymerodesmosine (HHMD), were isotopically labelled and then analysed by liquid-chromatography high-resolution accurate-mass mass spectrometry (LC-HRMS) and small-angle neutron scattering (SANS). The isotopic labelling followed by LC-HRMS confirmed the presence of one imino group in both HLNL and HHMD, making them more susceptible to degrade at low pH. The structural changes in collagen due to extreme changes in the pH and chrome tanning were highlighted by the SANS contrast variation between isotopic labelled and unlabelled crosslinks. This provided a better understanding of the interaction of natural crosslinks with the chromium sulphate in collagen suggesting that the development of a benign crosslinking method can help retain the intrinsic physical properties of the leather. This analytical method can also be applied to study artificial crosslinking in other collagenous tissues for biomedical applications. Graphical abstract
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320.
颜林林
(2024-01-30 09:58):
#paper doi:10.1101/2023.12.20.570816. bioRxiv, 2024, Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy. 本文使用甲基胆蒽烷(Methylcholanthrene,简称MCA,一种化学致癌物)诱导基因工程小鼠,构造了肉瘤动物模型,并以此作为研究体系,比较了新抗原疫苗和抗CTLA-4/抗PD-1的疗效。两种疗法都能促进肿瘤内特定CD8 T细胞的扩张,而新抗原疫苗的效应更为显著。文章通过单细胞转录组测序和单细胞免疫组库测序,分析了不同疗法导致了免疫微环境变化,揭示了这些细胞克隆型扩张与特定免疫治疗相关的表型和功能状态。新抗原疫苗与ICT联合使用显示出比单独使用任一治疗更高的疗效,为联合使用肿瘤免疫和免疫检查点治疗方法提供了证据支持。
bioRxiv : the preprint server for biology,
2024-Jan-26.
DOI: 10.1101/2023.12.20.570816
PMID: 38187708
Abstract:
The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate cancer by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether cancer vaccines and ICT …
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The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate cancer by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether cancer vaccines and ICT enhance anti-tumor immunity by distinct or overlapping mechanisms remains unclear. Here, we compared effective therapeutic tumor-specific mutant neoantigen (NeoAg) cancer vaccines with anti-CTLA-4 and/or anti-PD-1 ICT in preclinical models. Both NeoAg vaccines and ICT induce expansion of intratumoral NeoAg-specific CD8 T cells, though the degree of expansion and acquisition of effector activity was much more substantial following NeoAg vaccination. Further, we found that NeoAg vaccines are particularly adept at inducing proliferating and stem-like NeoAg-specific CD8 T cells. Single cell T cell receptor (TCR) sequencing revealed that TCR clonotype expansion and diversity of NeoAg-specific CD8 T cells relates to their phenotype and functional state associated with specific immunotherapies employed. Effective NeoAg vaccines and ICT required both CD8 and CD4 T cells. While NeoAg vaccines and anti-PD-1 affected the CD4 T cell compartment, it was to less of an extent than observed with anti-CTLA-4, which notably induced ICOSBhlhe40 Th1-like CD4 T cells and, when combined with anti-PD-1, a small subset of Th2-like CD4 T cells. Although effective NeoAg vaccines or ICT expanded intratumoral M1-like iNOS macrophages, NeoAg vaccines expanded rather than suppressed (as observed with ICT) M2-like CX3CR1CD206 macrophages, associated with the vaccine adjuvant. Further, combining NeoAg vaccination with ICT induced superior efficacy compared to either therapy in isolation, highlighting the utility of combining these modalities to eliminate cancer.
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