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161.
muton (2024-02-28 23:02):
#paper The Conceptual Structure of Human Relationships Across Modern and Historical Cultures preprint 人类社会复杂性的特征就是关系的复杂性,我们会和家庭、学校、工作、社区甚至社交网络的各类人群建立不同的关系。但我们应该如何理解如此复杂的人际关系系统?通过使用自然语言处理(NLP)、在线调查、实验室认知任务和计算建模,对世界各地的各种现代文化进行研究。(n = 20425)和跨越3,000年历史的古代文化,作者发现了关系概念的普遍表征空间,由五个主要维度组成(正式、主动、效价、交换、平等)和三个核心范畴(敌对、公共和私人关系)。这一工作推进了对人类社会性的理解。并且通过比较不同国家文化差异,作者发现中美存在巨大文化距离,在理解人际关系中的亲密程度时,美国人似乎更关注物理距离,而中国人更关注心理距离。
Abstract:
A defining characteristic of social complexity in Homo sapiens is the diversity of our relationships. We build various types of connections with people in families, schools, workplaces, neighborhoods, and online … >>>
A defining characteristic of social complexity in Homo sapiens is the diversity of our relationships. We build various types of connections with people in families, schools, workplaces, neighborhoods, and online communities. How do we make sense of such complex systems of human relationships? By using natural language processing, online surveys, laboratory cognitive tasks, and computational modelling on diverse modern cultures across the world (n = 20,425) and ancient cultures across 3,000 years of history, we discovered a universal representational space of relationship concepts, comprised of five principal dimensions (formality, activeness, valence, exchange, equality) and three core categories (hostile, public and private relationships). Our work reveals the fundamental cognitive constructs and cultural principles of relationship knowledge and advances our understanding of human sociality. <<<
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162.
尹志 (2024-02-28 22:09):
#paper An introduction to Topological Data Analysis: fundamental and practical aspects for data scientists doi: https://doi.org/10.48550/arXiv.1710.04019 生成式AI风光无两,Sora甚嚣尘上,虽然我还做不到这样的效果(对,我就是酸),但我却认为这不是终极方案,特别是对于物理世界、生物系统。The Bitter Lesson中对scaling law的强调甚至信奉,在语言、视频这样的领域有其价值,但生命科学、物理系统有数十亿年的的历史(物理系统应该是创始之初把),生命的演化、物理系统的本源,人类对其千百年来积累的原理性探索,应该是更优的先验。哦,回到这篇paper的主题。拓扑数据分析,是一种将系统的拓扑与几何性质引入分析建模过程,从而对系统获取更深刻的理解的工具。本篇综述对这个工具做了细致的讲解并对它的应用领域做了分析和tutorial。对拓扑数据分析这门技术的数学前置也做了简单但细致的介绍,主要是代数拓扑和计算几何。之所以有前面一段的碎碎念,就是因为我结合最近的一些实践,切实感受到拓扑和几何这些抽象的数学工具与生成式AI的结合,对生物系统和物理世界的描述,也许是优于目前暴力怼计算的一种更高效的建模方式,能够更深入系统的物理本质。如果你也相信物理系统和生命世界的简单高效的,是美丽简洁的,建议尝试一下这些新的技术。对了,这篇综述的revison信息是[Submitted on 11 Oct 2017 (v1), last revised 25 Feb 2021 (this version, v2)], 是不是说明了点什么呢?
Abstract:
Topological Data Analysis is a recent and fast growing field providing a setof new topological and geometric tools to infer relevant features for possiblycomplex data. This paper is a brief … >>>
Topological Data Analysis is a recent and fast growing field providing a setof new topological and geometric tools to infer relevant features for possiblycomplex data. This paper is a brief introduction, through a few selectedtopics, to basic fundamental and practical aspects of \tda\ for non experts. <<<
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163.
李翛然 (2024-02-28 18:11):
#paper A computational framework for neural network-based variational Monte Carlo with Forward Laplacian doi: https://doi.org/10.1038/s42256-024-00794-x 北大和字节跳动合作的文章,关注是因为一直在看计算化学领域的一些新进展。字节跳动和北京大学团队共同研究,针对神经网络变分蒙特卡罗(NN-VMC)在处理大规模量子系统时计算成本高的问题。 2. 研究团队创新性地提出了“Forward Laplacian”计算框架,通过前向传播直接高效计算神经网络相关拉普拉斯部分,显著提升NN-VMC计算效率。 3. 他们还设计了名为“LapNet”的高效神经网络结构,利用Forward Laplacian优势,大幅减少了模型训练所需的计算资源。 4. 结合Forward Laplacian和LapNet的NN-VMC方法在多种化学系统中展现出优越的性能,可准确计算绝对能量和相对能量,与实验数据和金标准计算方法吻合度高。 5. 尽管已有显著进步,但团队指出,未来还需要将更多化学和物理知识融入NN-VMC方法中以解决部分应用场景中的差异问题,同时Forward Laplacian有望在更广泛的量子力学及基于神经网络的偏微分方程求解领域发挥作用。
164.
前进 (2024-02-28 10:57):
#paper Mckenzie E M , Santhanam A , Ruan D ,et al.Multimodality image registration in the head‐and‐neck using a deep learning‐derived synthetic CT as a bridge[J].Medical Physics, 2020, 47(3).DOI:10.1002/mp.13976. 本文提出并验证一种利用深度学习驱动的跨模态综合技术的头颈多模式图像配准方法。 采用CycleGAN将MRI 转化为合成CT(sCT),将头颈部的MRI-CT多模态配准转化为sCT-CT的单模态配准。配准方法采用传统的B-spline方法。实验结果表明sCT→CT 配准精度好于MRI→CT。平均配准误差从9.8mm下降到6.0mm
IF:3.200Q1 Medical physics, 2020-Mar. DOI: 10.1002/mp.13976 PMID: 31853975
Abstract:
PURPOSE: To develop and demonstrate the efficacy of a novel head-and-neck multimodality image registration technique using deep-learning-based cross-modality synthesis.METHODS AND MATERIALS: Twenty-five head-and-neck patients received magnetic resonance (MR) and computed … >>>
PURPOSE: To develop and demonstrate the efficacy of a novel head-and-neck multimodality image registration technique using deep-learning-based cross-modality synthesis.METHODS AND MATERIALS: Twenty-five head-and-neck patients received magnetic resonance (MR) and computed tomography (CT) (CTaligned ) scans on the same day with the same immobilization. Fivefold cross validation was used with all of the MR-CT pairs to train a neural network to generate synthetic CTs from MR images. Twenty-four of 25 patients also had a separate CT without immobilization (CTnon-aligned ) and were used for testing. CTnon-aligned 's were deformed to the synthetic CT, and compared to CTnon-aligned registered to MR. The same registrations were performed from MR to CTnon-aligned and from synthetic CT to CTnon-aligned . All registrations used B-splines for modeling the deformation, and mutual information for the objective. Results were evaluated using the 95% Hausdorff distance among spinal cord contours, landmark error, inverse consistency, and Jacobian determinant of the estimated deformation fields.RESULTS: When large initial rigid misalignment is present, registering CT to MRI-derived synthetic CT aligns the cord better than a direct registration. The average landmark error decreased from 9.8 ± 3.1 mm in MR→CTnon-aligned to 6.0 ± 2.1 mm in CTsynth →CTnon-aligned deformable registrations. In the CT to MR direction, the landmark error decreased from 10.0 ± 4.3 mm in CTnon-aligned →MR deformable registrations to 6.6 ± 2.0 mm in CTnon-aligned →CTsynth deformable registrations. The Jacobian determinant had an average value of 0.98. The proposed method also demonstrated improved inverse consistency over the direct method.CONCLUSIONS: We showed that using a deep learning-derived synthetic CT in lieu of an MR for MR→CT and CT→MR deformable registration offers superior results to direct multimodal registration. <<<
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165.
盼盼 (2024-02-27 16:38):
DOI: 10.1038/s41586-018-0453-z 目前我们已经发现数千种长链非编码RNA(lncRNA),但是明确功能的只有十几种。德克萨斯西南医学研究中心Mendell教授发现lncRNA-NORAD可以在维持基因组稳定性上非常重要。此外,还报道了PUMILIO是NORAD唯一相互作用的RNA结合蛋白,但是相关的作用机制我们并不清楚。最近 哈弗-麻省理工学院lander教授提出了NORAD和RNA结合蛋白PUMILIO的相互作用,对NORAD功能发挥具有重要作用。NORAD和PUMILIO结合后,NORAD调节PUMILIO组装拓补异构酶复合物的能力,该复合物在维持基因组稳定性具有重要作用。实验证明细胞在PUMILIO敲除后的表型,与PUMILIO敲除表型密切相关,都表现为染色质分离增加,复制叉速度降低和细胞周期改变。在PUMILIO正常表达的细胞,补充NORAD,可以补救NORAD缺失引起的基因组不稳定,但是在NORAD的作用位点缺失以后,挽救效果就很差。这说明NORAD是通过特定位点与PUMILIO相互作用,促进拓补异构酶复合物组装并参与维持基因组稳定性。但是对于NORAD与PUMILIO的相互作用如何促进拓补异构酶复合物组装的,lander教授提出了多个可能的机制,这些机制还有待进一步实验验证。
IF:50.500Q1 Nature, 2018-09. DOI: 10.1038/s41586-018-0453-z PMID: 30150775
Abstract:
The human genome contains thousands of long non-coding RNAs, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen. A specific long non-coding RNA-non-coding RNA … >>>
The human genome contains thousands of long non-coding RNAs, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen. A specific long non-coding RNA-non-coding RNA activated by DNA damage (NORAD)-has recently been shown to be required for maintaining genomic stability, but its molecular mechanism is unknown. Here we combine RNA antisense purification and quantitative mass spectrometry to identify proteins that directly interact with NORAD in living cells. We show that NORAD interacts with proteins involved in DNA replication and repair in steady-state cells and localizes to the nucleus upon stimulation with replication stress or DNA damage. In particular, NORAD interacts with RBMX, a component of the DNA-damage response, and contains the strongest RBMX-binding site in the transcriptome. We demonstrate that NORAD controls the ability of RBMX to assemble a ribonucleoprotein complex-which we term NORAD-activated ribonucleoprotein complex 1 (NARC1)-that contains the known suppressors of genomic instability topoisomerase I (TOP1), ALYREF and the PRPF19-CDC5L complex. Cells depleted for NORAD or RBMX display an increased frequency of chromosome segregation defects, reduced replication-fork velocity and altered cell-cycle progression-which represent phenotypes that are mechanistically linked to TOP1 and PRPF19-CDC5L function. Expression of NORAD in trans can rescue defects caused by NORAD depletion, but rescue is significantly impaired when the RBMX-binding site in NORAD is deleted. Our results demonstrate that the interaction between NORAD and RBMX is important for NORAD function, and that NORAD is required for the assembly of the previously unknown topoisomerase complex NARC1, which contributes to maintaining genomic stability. In addition, we uncover a previously unknown function for long non-coding RNAs in modulating the ability of an RNA-binding protein to assemble a higher-order ribonucleoprotein complex. <<<
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166.
DeDe宝 (2024-02-15 16:06):
#paper doi:10.7554/eLife.91825.3 A spatial-attentional mechanism underlies action-related distortions of time judgment,eLife 时间绑定(Temporal binding)指一种动作和稍微延迟的感官事件之间的时间吸引力的错觉,由动作绑定(action binding,即被报告为较晚发生的动作)和结果绑定(outcome binding,即被报告为较早发生的感觉事件)组成。然而,在使用Libet时钟方法测量时间判断时,视觉空间注意力的影响被严重忽视。结果绑定通常是通过比较动作声音(AS)条件和仅声音(SO)条件来获得的,被试报告声音播放时时钟指针指向的位置,AS 条件下报告的时间比 SO 条件下的报告时间早。动作绑定通过比较AS条件和AO条件,AS 条件下报告的按键时间晚于 AO 条件下报告的按键时间。在本研究的四个实验中,研究者使用时钟方法证明了由动作和感觉刺激引起的时间绑定中注意力调节的不同模式。此外,单独使用注意力测量的计算模型可以重现时间绑定效应,为时间绑定的注意力假设提供强有力的支持证据。
IF:6.400Q1 eLife, 2024. DOI: 10.7554/eLife.91825.3
Abstract:
Temporal binding has been understood as an illusion in timing judgment. When an action triggers an outcome (e.g. a sound) after a brief delay, the action is reported to occur … >>>
Temporal binding has been understood as an illusion in timing judgment. When an action triggers an outcome (e.g. a sound) after a brief delay, the action is reported to occur later than if the outcome does not occur, and the outcome is reported to occur earlier than a similar outcome not caused by an action. We show here that an attention mechanism underlies the seeming illusion of timing judgment. In one method, participants watch a rotating clock hand and report event times by noting the clock hand position when the event occurs. We find that visual spatial attention is critically involved in shaping event time reports made in this way. This occurs because action and outcome events result in shifts of attention around the clock rim, thereby biasing the perceived location of the clock hand. Using a probe detection task to measure attention, we show a difference in the distribution of visual spatial attention between a single-event condition (sound only or action only) and a two-event agency condition (action plus sound). Participants accordingly report the timing of the same event (the sound or the action) differently in the two conditions: spatial attentional shifts masquerading as temporal binding. Furthermore, computational modeling based on the attention measure can reproduce the temporal binding effect. Studies that use time judgment as an implicit marker of voluntary agency should first discount the artefactual changes in event timing reports that actually reflect differences in spatial attention. The study also has important implications for related results in mental chronometry obtained with the clock-like method since Wundt, as attention may well be a critical confounding factor in the interpretation of these studies. <<<
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167.
龙海晨 (2024-02-09 19:34):
#paper Ahmed Mostafa G, Mohamed Ibrahim H, Al Sayed Shehab A, Mohamed Magdy S, AboAbdoun Soliman N, Fathy El-Sherif D. Up-regulated serum levels of interleukin (IL)-17A and IL-22 in Egyptian pediatric patients with COVID-19 and MIS-C: Relation to the disease outcome. Cytokine. 2022 Jun;154:155870. doi: 10.1016/j.cyto.2022.155870. Epub 2022 Apr 4. PMID: 35398721; PMCID: PMC8977483.这是一篇研究新冠感染儿童血清中各种细胞因子与新冠严重程度的文章。检测患者40名(其中 18 名患者患有 COVID-19,22 名患者患有多系统炎症综合征“MIS-C”)年龄从两个月到16周岁,48名健康儿童作为对照组。COVID-19 和 MIS-C 患者的血清 IL-17A 和 IL-22 水平显着高于健康对照儿童。患者的血清 IL-17A 和 IL-22 水平均升高。90% 的患者发现 CRP 和血清铁蛋白水平升高。IL-17和IL-22都被认为是组织信号细胞因子,有利于肺、皮肤和胃肠道等上皮屏障器官的保护和再生。IL-17 和 IL-22 在宿主抵御微生物以及急性和慢性炎症性疾病的发展中发挥着重要作用。但康复的患者与死亡的患者生前留存的血清中对比 IL-17A、IL-22 没有显著差异, IL-17A、IL-22 的升高与否不能作为预后指标。
IF:3.700Q2 Cytokine, 2022-06. DOI: 10.1016/j.cyto.2022.155870 PMID: 35398721
Abstract:
Both IL-17A and IL-22 share cellular sources and signaling pathways. They have synergistic action on epithelial cells to stimulate their production of antimicrobial peptides which are protective against infections. However, … >>>
Both IL-17A and IL-22 share cellular sources and signaling pathways. They have synergistic action on epithelial cells to stimulate their production of antimicrobial peptides which are protective against infections. However, both interleukins may contribute to ARDS pathology if their production is not controlled. This study aimed to investigate serum levels of IL-17A and IL-22 in relation to the disease outcome in patients with SARS-CoV-2. Serum IL-17A and IL-22 were measured by ELISA in 40 patients with SARS-CoV-2, aged between 2 months and 16 years, (18 had COVID-19 and 22 had multisystem inflammatory syndrome in children "MIS-C") in comparison to 48 age- and sex-matched healthy control children. Patients with COVID-19 and MIS-C had significantly higher serum IL-17A and IL-22 levels than healthy control children (P < 0.001). Increased serum IL-17A and IL-22 levels were found in all patients. Elevated CRP and serum ferritin levels were found in 90% of these patients. Lymphopenia, neutrophilia, neutropenia, thrombocytopenia and elevated ALT, LDH and D-dimer were found in 45%, 42.5 %, 2.5%, 30%, 32.5%, 82.5%, and 65%, respectively of these patients. There were non-significant differences between patients who recovered and those who died or had a residual illness in serum levels of IL-17A, IL-22 and the routine inflammatory markers of COVID-19. In conclusions, serum IL-17A and IL-22 levels were up-regulated in all patients with COVID-19 and MIS-C. Levels of serum IL-17A, IL-22 and the routine inflammatory markers of COVID-19 were not correlated with the disease outcome. Our conclusions are limited by the sample size. <<<
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168.
na na na (2024-01-31 23:53):
#paper doi: 10.1038/s41591-023-02371-y. Epub 2023 May 29.Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance 。T细胞是肿瘤免疫中非常重要的存在,肿瘤细胞被发现之后,T细胞就会以指数方式增殖向效应T细胞和记忆T细胞分化,快速消灭外来病原体/肿瘤,但经历不断的抗原刺激和免疫抑制信号的干扰,一些T细胞也会进入疲软期,分化为功能丧失的状态,称为T细胞耗竭(TEX)。MD安德森癌症中心对T细胞状态的广泛多样性以及它们在复杂的肿瘤微环境中的关系和作用提供了更深入的了解,为理解癌症免疫治疗效果带来了新的视角。文章主要提出了一个新的概念:T细胞应激反应状态(T cell stress response state),是指当细胞面临不利环境或压力时触发的一系列变化,以保持细胞的稳态和适应环境。适度的应激刺激可以激活细胞的防御机制,促进修复和适应能力的提高。在肿瘤中,TSTR细胞可以被认为是一类“压力过大”的T细胞。但与TEX细胞的不同,T细胞是通过两条截然不同的途径分化为TEX细胞与TSTR细胞。新的T细胞类型的发现对指导之后的肿瘤免疫微环境分析很大的价值,值得对作者数据再次进行挖掘,例如得到新的细胞亚型signature。推荐给做肿瘤科研的小伙伴,值得一读。
IF:58.700Q1 Nature medicine, 2023-Jun. DOI: 10.1038/s41591-023-02371-y PMID: 37248301
Abstract:
Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes … >>>
Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes across 16 cancer types, uncovering previously undescribed T cell states and heterogeneous subpopulations of follicular helper, regulatory and proliferative T cells. We identified a unique stress response state, T, characterized by heat shock gene expression. T cells are detectable in situ in the tumor microenvironment across various cancer types, mostly within lymphocyte aggregates or potential tertiary lymphoid structures in tumor beds or surrounding tumor edges. T cell states/compositions correlated with genomic, pathological and clinical features in 375 patients from 23 cohorts, including 171 patients who received immune checkpoint blockade therapy. We also found significantly upregulated heat shock gene expression in intratumoral CD4/CD8 cells following immune checkpoint blockade treatment, particularly in nonresponsive tumors, suggesting a potential role of T cells in immunotherapy resistance. Our well-annotated T cell reference maps, web portal and automatic alignment/annotation tool could provide valuable resources for T cell therapy optimization and biomarker discovery. <<<
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169.
林海onrush (2024-01-31 23:47):
#paper, doi.org/10.1038/s41586-023-06747-5, Solving olympiad geometry without human demonstrations, 此文介绍了一种解决数学奥林匹克竞赛中复杂几何问题的创新方法。论文中提出的AlphaGeometry是一种结合神经语言模型和符号推理引擎的神经符号系统。它能够生成包括定理和证明在内的合成数据,有效克服了此领域训练数据的稀缺性。AlphaGeometry在解决难度较高的奥林匹克级别问题方面表现出色,其性能可与国际数学奥林匹克竞赛(IMO)金牌得主相媲美。它不仅能以人类可读格式合成证明,还发现了一个已知IMO定理的更通用版本。AlphaGeometry在自动定理证明领域取得了重要进展,展示了神经符号系统在解决复杂数学问题方面的潜力,为不依赖人类生成数据的人工智能研究提供了新方向。这一发展对数学和人工智能领域产生深远影响。
IF:50.500Q1 Nature, 2024-Jan. DOI: 10.1038/s41586-023-06747-5 PMID: 38233616
Abstract:
Proving mathematical theorems at the olympiad level represents a notable milestone in human-level automated reasoning, owing to their reputed difficulty among the world's best talents in pre-university mathematics. Current machine-learning … >>>
Proving mathematical theorems at the olympiad level represents a notable milestone in human-level automated reasoning, owing to their reputed difficulty among the world's best talents in pre-university mathematics. Current machine-learning approaches, however, are not applicable to most mathematical domains owing to the high cost of translating human proofs into machine-verifiable format. The problem is even worse for geometry because of its unique translation challenges, resulting in severe scarcity of training data. We propose AlphaGeometry, a theorem prover for Euclidean plane geometry that sidesteps the need for human demonstrations by synthesizing millions of theorems and proofs across different levels of complexity. AlphaGeometry is a neuro-symbolic system that uses a neural language model, trained from scratch on our large-scale synthetic data, to guide a symbolic deduction engine through infinite branching points in challenging problems. On a test set of 30 latest olympiad-level problems, AlphaGeometry solves 25, outperforming the previous best method that only solves ten problems and approaching the performance of an average International Mathematical Olympiad (IMO) gold medallist. Notably, AlphaGeometry produces human-readable proofs, solves all geometry problems in the IMO 2000 and 2015 under human expert evaluation and discovers a generalized version of a translated IMO theorem in 2004. <<<
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170.
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 … >>>
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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171.
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。
IF:50.500Q1 Nature, 2023. DOI: 10.1038/s41586-023-06377-x
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 … >>>
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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172.
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。
IF:11.700Q1 Science advances, 2022-Mar-25. DOI: 10.1126/sciadv.abj4383 PMID: 35319988
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 … >>>
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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173.
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
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 … >>>
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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174.
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
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 … >>>
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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175.
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。
IF:22.500Q1 JAMA psychiatry, 2024-Apr-01. DOI: 10.1001/jamapsychiatry.2023.5083 PMID: 38198165
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 … >>>
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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176.
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 … >>>
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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177.
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。
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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 … >>>
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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179.
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 … >>>
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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180.
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。
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 … >>>
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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