当前共找到 1276 篇文献分享,本页显示第 281 - 300 篇。
281.
前进 (2024-06-30 22:29):
#paper Liu R , Li Z , Fan X ,et al.Learning Deformable Image Registration from Optimization: Perspective, Modules, Bilevel Training and Beyond[J]. 2020.DOI:10.48550/arXiv.2004.14557. 论文提出了一个新的基于深度学习的框架,旨在通过多尺度传播优化微分同胚模型来整合传统变形配准方法和基于深度学习的方法的优势,并避免它们的局限性。具体来说,作者提出了一个通用的优化模型来解决微分同胚配准问题,并开发了一系列可学习的架构,以从粗到细的学习图像特征完成配准。此外,论文还提出了一种新颖的双层自调整训练策略,允许高效地搜索任务特定的超参数,这增加了对各种类型数据的灵活性,同时减少了计算和人力负担。 作者多种数据集上进行了配准实验,包括大脑MRI数据的图像到图谱配准和肝脏CT数据的图像到图像配准。实验结果表明,所提出的方法在保持微分同胚的同时,达到了最先进的性能。此外,作者还将其框架应用于多模态图像配准,并研究了其配准如何支持医学图像分析的下游任务,包括多模态融合和图像分割。
Abstract:
Conventional deformable registration methods aim at solving an optimizationmodel carefully designed on image pairs and their computational costs areexceptionally high. In contrast, recent deep learning based approaches canprovide fast deformation … >>>
Conventional deformable registration methods aim at solving an optimizationmodel carefully designed on image pairs and their computational costs areexceptionally high. In contrast, recent deep learning based approaches canprovide fast deformation estimation. These heuristic network architectures arefully data-driven and thus lack explicit geometric constraints, e.g.,topology-preserving, which are indispensable to generate plausibledeformations. We design a new deep learning based framework to optimize adiffeomorphic model via multi-scale propagation in order to integrateadvantages and avoid limitations of these two categories of approaches.Specifically, we introduce a generic optimization model to formulatediffeomorphic registration and develop a series of learnable architectures toobtain propagative updating in the coarse-to-fine feature space. Moreover, wepropose a novel bilevel self-tuned training strategy, allowing efficient searchof task-specific hyper-parameters. This training strategy increases theflexibility to various types of data while reduces computational and humanburdens. We conduct two groups of image registration experiments on 3D volumedatasets including image-to-atlas registration on brain MRI data andimage-to-image registration on liver CT data. Extensive results demonstrate thestate-of-the-art performance of the proposed method with diffeomorphicguarantee and extreme efficiency. We also apply our framework to challengingmulti-modal image registration, and investigate how our registration to supportthe down-streaming tasks for medical image analysis including multi-modalfusion and image segmentation. <<<
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282.
尹志 (2024-06-30 17:56):
#paper DOI: 10.1038/s41534-017-0048-9 Coherent Ising machines—optical neural networks operating at the quantum limit. npj Quantum Inf 3, 49 (2017). 这个工作介绍了一种新型的量子计算方案,相干ising机(CIM)。区别于传统的量子计算方案,CIM有着特别的实用优势,比如对退相干时间没有要求。当然这和它的设计思路相关。从2011年理论方案出现,到目前真机落地的发展,其基本的原理没有变化,区别于传统量子计算在叠加态下进行逻辑计算,再统一进行readout的操作,CIM一开始就采取迭代读取的方式,在每一轮计算(演化)后,进行读读取测量,对系统状态(比如相位情况)进行计算反馈,从而在足够的迭代次数后获得保真度较高的计算结果。该方案特别适合目前的各类优化问题的解决,如果将传统的量子计算方案(量子电路为主)看成瀑布流的开发思路,那么CIM应该就是迭代的敏捷开发。CIM确实是很有意思的想法,希望能够在这个量子计算范式下结合AI做一些有意思的探索。
Abstract:
AbstractIn this article, we will introduce the basic concept and the quantum feature of a novel computing system, coherent Ising machines, and describe their theoretical and experimental performance. We start … >>>
AbstractIn this article, we will introduce the basic concept and the quantum feature of a novel computing system, coherent Ising machines, and describe their theoretical and experimental performance. We start with the discussion how to construct such physical devices as the quantum analog of classical neuron and synapse, and end with the performance comparison against various classical neural networks implemented in CPU and supercomputers. <<<
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283.
惊鸿 (2024-06-30 17:55):
#paper No CRISPR: oddball ‘jumping gene’ enzyme edits genomes without breaking DNA Pub Date : 2024-06-27 DOI : 10.1038/d41586-024-02141-x 阅读了关于利用跳跃基因进行基因编辑的研究论文,我对其科学创新和潜在应用产生了兴趣。这项技术通过利用细菌中的跳跃基因,提供了一种新的基因编辑手段,能够在不破坏DNA的情况下进行大规模的基因序列操作。与传统的CRISPR-Cas9技术相比,它在理论上能够进行更精确和更少副作用的基因编辑。 论文中提到的IS110和IS1111家族的转座元件,以及它们使用的RNA引导系统,展示了基因编辑领域的新方向。这项技术在细菌中的成功应用,为未来可能的人类细胞应用提供了初步证据,尽管在实际应用于人类之前,还需要进一步的研究和优化。 此外,这项技术在医学上的应用前景,尤其是在治疗遗传性疾病和癌症方面,是值得关注的。尽管目前还存在一些技术挑战,但科研人员的努力和创新思维为解决这些问题提供了希望。 总的来说,这项研究为基因编辑技术的发展提供了新的视角,也为未来的生物医学研究开辟了新的可能性。
IF:50.500Q1 Nature, 2024-Jul. DOI: 10.1038/d41586-024-02141-x PMID: 38937599
没有CRISPR:奇怪的“跳跃基因”酶在不破坏DNA的情况下编辑基因组
Abstract: No abstract available.
284.
半面阳光 (2024-06-30 17:33):
#paper DOI: 10.1002/pd.5620 Prenatal Diagnosis, 2019, Fetal fraction and noninvasive prenatal testing: what clinicians need to know. 这是一篇综述文章,作者总结了fetal fraction(即胎儿cfDNA浓度)在理解和解读NIPT检测结果中作为重要参数的作用。综述内容分为以下几个方面。第一,fetal freaction的定义,如何理解fetal fraction的“高”和“低”;第二fetal fraction的来源及其数值高低受到哪些生物学因素的影响;第三,NIPT流程中如何计算fetal fraction以及fetal fraction这一参数设置对NIPT结果的影响;第四,由于low fetal fraction导致NIPT结果no-call时,有什么备选方案。
IF:2.700Q2 Prenatal diagnosis, 2020-01. DOI: 10.1002/pd.5620 PMID: 31821597
Abstract:
The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal … >>>
The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of samples with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice. <<<
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285.
哪有情可长 (2024-06-30 16:12):
#paper Maize smart-canopy architecture enhances yield at high densities, Nature, 6 June 2024, DOI: 10.1038/s41586-024-07669-6.玉米耐密性是决定玉米单位面积产量的关键因素。该实验室早期发现了一个玉米株型上部叶片夹角紧凑、中下部叶夹角相对展开的自然突变体材料,称为智慧株型,该基因命名为lac1,然后利用图位克隆,发现该基因编码一个类固醇C-22 羟化酶(DWF4),其外显子上一个273bp的转座子插入导致编码蛋白提前终止。利用CRISPR/Cas9基因编辑技术对lac1进行了编辑,纯合敲除系均展现出“上紧下松”智慧株型表型。连续4年在4个地点对lac1突变体、敲除系和F1杂交种进行了不同种植密度的田间产量试验,结果显示在高密度种植条件下,携带lac1突变等位基因的“上紧下松”株型可以显著增加群体中下部冠层透光率、增强穗位叶净光合速率、削弱密植群体的避荫反应,最终促进玉米群体产量显著增加。该实验室前期分子实验验证调控叶夹角的转录因子RAVL1可以激活lac1基因的表达,控制玉米叶环区油菜素内酯的积累,从而影响叶夹角的大小。后续利用遮荫和正常对照发现遮荫后,lac1表达下降,后续研究发现转录因子RAVL1仅能与phyA互作,而不能与phyB互作,随着种植密度增加,红光:远红光的比例(R/FR)降低,促进phyA蛋白积累,phyA与RAVL1互作并促进RAVL1蛋白的降解,从而削弱RAVL1对lac1的激活作用,最终减小高密度条件下的玉米叶夹角。在lac1_突变体中,phyA-RAVL1介导的光信号通路被阻断,从而削弱lac1突变体对遮荫的响应。
IF:50.500Q1 Nature, 2024-Jun-12. DOI: 10.1038/s41586-024-07669-6 PMID: 38866052
Abstract:
Increasing planting density is a key strategy to enhance maize yields. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to … >>>
Increasing planting density is a key strategy to enhance maize yields. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis, amongst other features. Here, we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant possessing upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and weakened shade-avoidance responses under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby attenuating RAVL1 activation of lac1 and reducing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate lac1 boosts maize yields under high densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize. <<<
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286.
Vincent (2024-06-30 16:11):
#paper doi:https://doi.org/10.1038/s41556-020-00620-7, Nat Cell Biol,2021, CRISPR technologies for precise epigenome editing. 这篇论文综述了CRISPR/Cas系统在表观基因组编辑中的应用和进展。文章介绍了CRISPR/Cas9系统的基本原理,以及如何利用Cas9(dCas9)招募表观遗传修饰酶,实现特定基因的转录激活或抑制。文章回顾了一些细胞和动物模型的应用实例,展示了CRISPR技术在研究基因功能和治疗疾病中的潜力,并指出了现有的技术挑战与优化策略,包括编辑效率、脱靶效应和表观遗传修饰的动态性。最后展望了CRISPR技术在表观基因组编辑领域的未来发展方向,强调需要进一步研究以提高技术的特异性和稳定性。
IF:17.300Q1 Nature cell biology, 2021-01. DOI: 10.1038/s41556-020-00620-7 PMID: 33420494
CRISPR技术用于精确的表观基因组编辑
Abstract:
The epigenome involves a complex set of cellular processes governing genomic activity. Dissecting this complexity necessitates the development of tools capable of specifically manipulating these processes. The repurposing of prokaryotic … >>>
The epigenome involves a complex set of cellular processes governing genomic activity. Dissecting this complexity necessitates the development of tools capable of specifically manipulating these processes. The repurposing of prokaryotic CRISPR systems has allowed for the development of diverse technologies for epigenome engineering. Here, we review the state of currently achievable epigenetic manipulations along with corresponding applications. With future optimization, CRISPR-based epigenomic editing stands as a set of powerful tools for understanding and controlling biological function. <<<
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表观基因组涉及一组控制基因组活动的复杂细胞过程。剖析这种复杂性需要开发能够专门操作这些过程的工具。原核CRISPR系统的重新利用使得表观基因组工程的多样化技术得以开发。在这里,我们回顾了目前可实现的表观遗传操作的状态以及相应的应用。随着未来的优化,基于CRISPR的表观基因组编辑将成为一套用于理解和控制生物功能的强大工具。
287.
徐炳祥 (2024-06-30 14:57):
#paper doi:10.1038/s41588-021-00784-4 Nature genetics, 2021, Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics。对染色质区室结构(chromatin compartments)的识别是三维基因组学研究的重要课题。本研究中作者基于Flory–Huggins聚合物理论预言了在染色质构象捕获实验中,检测到不同位于不同区室的染色质片段聚合倾向与片段长度和相同/不同区室片段聚合能差异之乘积成正比。在此理论指导下,作者指出实验前预先对基因组施以不同时间的酶解,进而控制片段化后染色质长度,便可在不同水平和维度检查染色质区室结构。作者发现过度预酶解可导致实验无法检测区室和染色质环结构,与核纤层关联的结构域对预酶解是稳定的,而与核斑或多数蛋白有关的结构与对预酶解是敏感的。本研究为染色质构象捕获实验的动力学提供了一个新架构,也为解释一些实验现象提供了新思路。
IF:31.700Q1 Nature genetics, 2021-03. DOI: 10.1038/s41588-021-00784-4 PMID: 33574602
Abstract:
Nuclear compartmentalization of active and inactive chromatin is thought to occur through microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are … >>>
Nuclear compartmentalization of active and inactive chromatin is thought to occur through microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are not known. We developed liquid chromatin Hi-C to map the stability of associations between loci. Before fixation and Hi-C, chromosomes are fragmented, which removes strong polymeric constraint, enabling detection of intrinsic locus-locus interaction stabilities. Compartmentalization is stable when fragments are larger than 10-25 kb. Fragmentation of chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Lamin-associated domains are most stable, whereas interactions for speckle- and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics. <<<
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288.
张浩彬 (2024-06-30 10:34):
@paper https://doi.org/10.48550/arXiv.2403.10131 RAFT: Adapting Language Model to Domain Specific RAG 对我而言很有启发性的paper。在大型文本数据集上预训练大型语言模型(LLMs)已成为一种标准范式。当将这些LLMs用于许多下游应用时,通常会将新的知识(例如,时效性新闻或私有领域知识)通过基于RAG(Retrieval-Augmented Generation,检索增强生成)的提示或微调,融入到预训练模型中。然而,模型如何以最优方式获取这种新知识仍然是一个开放的问题。在这篇论文中,提出了检索增强微调(Retrieval Augmented Fine Tuning,RAFT),简单来说,就是你要用rag的东西微调一下,并使用思维链熟悉一下要做的事情。当然,rag本身和微调就是两个套路,现在合在一起,似乎有点本末倒置,这也是这篇论文我认为没有讨论清楚的地方。不过这些不清楚的地方也是新的研究空间。
Abstract:
Pretraining Large Language Models (LLMs) on large corpora of textual data isnow a standard paradigm. When using these LLMs for many downstreamapplications, it is common to additionally bake in new … >>>
Pretraining Large Language Models (LLMs) on large corpora of textual data isnow a standard paradigm. When using these LLMs for many downstreamapplications, it is common to additionally bake in new knowledge (e.g.,time-critical news, or private domain knowledge) into the pretrained modeleither through RAG-based-prompting, or fine-tuning. However, the optimalmethodology for the model to gain such new knowledge remains an open question.In this paper, we present Retrieval Augmented FineTuning (RAFT), a trainingrecipe that improves the model's ability to answer questions in a "open-book"in-domain settings. In RAFT, given a question, and a set of retrieveddocuments, we train the model to ignore those documents that don't help inanswering the question, which we call, distractor documents. RAFT accomplishesthis by citing verbatim the right sequence from the relevant document thatwould help answer the question. This coupled with RAFT's chain-of-thought-styleresponse helps improve the model's ability to reason. In domain-specific RAG,RAFT consistently improves the model's performance across PubMed, HotpotQA, andGorilla datasets, presenting a post-training recipe to improve pre-trained LLMsto in-domain RAG. RAFT's code and demo are open-sourced atgithub.com/ShishirPatil/gorilla. <<<
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289.
李翛然 (2024-06-28 14:45):
#paper: doi.org/10.1080/13543776.2024.2369630 Inhibition of GTPase KRASG12D: a review of patent literature 最近发了篇paper 专利回顾的。我们做了个国产替代, 药物上市太墨迹了,就用ai设计了一个荧光探针试剂盒,以后所有想做KRAS,以及KRAS的多突变药物的,直接买这个试剂盒可以测试药物活性,很方便,对标产品1.6万一盒,我们才6000. 国际上就我们2家。 欢迎大家采购。 核心原理不难,就是把一个对标的有效抑制剂,尾部挂上荧光探针,用AI把linker设计出来,再加一些好合成的条件。 今年这个AI也要发一个paper ,大家别急,带条件生成的ai,也是国际上第一个。另外预告一下,今年我们会用光量子计算机,设计蛋白质~~
Abstract:
INTRODUCTION: KRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an 'undruggable target.' Among the … >>>
INTRODUCTION: KRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an 'undruggable target.' Among the various KRAS mutations, KRASG12D is highly prevalent and represents a promising therapeutic target, yet there are currently no approved inhibitors for it.AREA COVERED: This review summarizes numerous patents and literature featuring inhibitors or degraders of KRASG12D through searching relevant information in PubMed, SciFinder and Web of Science databases from 2021 to February 2024, providing an overview of the research progress on inhibiting KRASG12D in terms of design strategies, chemical structures, biological activities, and clinical advancements.EXPERT OPINION: Since the approval of AMG510 (Sotorasib), there has been an increasing focus on the inhibition of KRASG12D, leading to numerous reports of related inhibitors and degraders. Among them, MRTX1133, as the first KRASG12D inhibitor to enter clinical trials, has demonstrated excellent tumor suppression in various KRASG12D-bearing human tumor xenograft models. It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRASG12D also holds significant potential. <<<
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290.
颜林林 (2024-06-19 06:01):
#paper doi:10.1038/s41559-024-02420-w, Nature Ecology & Evolution, 2024, African elephants address one another with individually specific name-like calls. 这篇研究很有意思,作者通过对非洲象发出的声音及其行为进行分析,首次确认了非洲象能够使用个体特定的叫声来识别和称呼其他象。之所以开展这项研究,是因为作者作为生态学家,观察到非洲象拥有广泛的声音交流和丰富的社会关系,因此他推测大象很可能会给彼此起名字。于是他们录制了大象发出的声音,并使用随机森林等机器学习方法,将声音片段与该声音的接收对象建立联系,预测准确度达到27.5%,显著超过作为对照的随机声音的效果。更有趣的是,他们将声音回放给大象,并观察其反应,确认了当大象听到“自己的名字”时,它们会发出更大的叫声,并更快地向扬声器移动。作者认为,这项研究是一个“非常有希望的开端”,将“引出一系列可以研究的其他问题”,比如大象是否也会说出地点的名字,甚至会用第三人称谈论彼此,而这种称呼个体同类的社会需求,很可能会是语言起源的前身。
IF:13.900Q1 Nature ecology & evolution, 2024-Jun-10. DOI: 10.1038/s41559-024-02420-w PMID: 38858512
Abstract:
Personal names are a universal feature of human language, yet few analogues exist in other species. While dolphins and parrots address conspecifics by imitating the calls of the addressee, human … >>>
Personal names are a universal feature of human language, yet few analogues exist in other species. While dolphins and parrots address conspecifics by imitating the calls of the addressee, human names are not imitations of the sounds typically made by the named individual. Labelling objects or individuals without relying on imitation of the sounds made by the referent radically expands the expressive power of language. Thus, if non-imitative name analogues were found in other species, this could have important implications for our understanding of language evolution. Here we present evidence that wild African elephants address one another with individually specific calls, probably without relying on imitation of the receiver. We used machine learning to demonstrate that the receiver of a call could be predicted from the call's acoustic structure, regardless of how similar the call was to the receiver's vocalizations. Moreover, elephants differentially responded to playbacks of calls originally addressed to them relative to calls addressed to a different individual. Our findings offer evidence for individual addressing of conspecifics in elephants. They further suggest that, unlike other non-human animals, elephants probably do not rely on imitation of the receiver's calls to address one another. <<<
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291.
DeDe宝 (2024-06-06 21:01):
#paper Differential Recruitment of the Hippocampus, Medial Prefrontal Cortex, and the Human Motion Complex during Path Integration in Humans. J Neurosci. 2007. 路径整合能力指监测自我运动,追踪方向和位置的变化的能力,是空间导航和认知地图发展的关键。之前的研究表明动物的路径整合主要由头朝向细胞(head-direction)、网格细胞(grid cell)和位置细胞(place cell)支持,然而,在本文发表之前,对于人类路径整合细胞的脑网络基础还不清楚。因此,研究者检验人类被试在三角范式中的fMRI信号,以探究人类路径整合的脑网络是否与啮齿动物、非人类哺乳动物相似。研究主要结果如下:1-更强的右侧海马信号预测了更准确的路径整合表现;2-被试间反应一致性波动与双侧海马和内侧前额叶激活负相关;3-双侧人体运动复合体 (hMT+)回路与个体路径整合能力共变。综上,该研究首次证明视觉路径整合与海马、内侧前额叶、人体运动复合体有关。
Abstract:
Path integration, the ability to sense self-motion for keeping track of changes in orientation and position, constitutes a fundamental mechanism of spatial navigation and a keystone for the development of … >>>
Path integration, the ability to sense self-motion for keeping track of changes in orientation and position, constitutes a fundamental mechanism of spatial navigation and a keystone for the development of cognitive maps. Whereas animal path integration is predominantly supported by the head-direction, grid, and place cell systems, the neural foundations are not well understood in humans. Here we used functional magnetic resonance imaging and a virtual rendition of a triangle completion paradigm to test whether human path integration recruits a cortical system similar to that of rodents and nonhuman primates. Participants traveled along two legs of a triangle before pointing toward the starting location. In accordance with animal models, stronger right hippocampal activation predicted more accurate updating of the starting location on a trial-by-trial basis. Moreover, between-subjects fluctuations in response consistency were negatively correlated with bilateral hippocampal and medial prefrontal activation, and bilateral recruitment of the human motion complex (hMT+) covaried with individual path integration capability. Given that these effects were absent in a perceptual control task, the present study provides the first evidence that visual path integration is related to the dynamic interplay of self-motion processing in hMT+, higher-level spatial processes in the hippocampus, and spatial working memory in medial prefrontal cortex. <<<
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292.
龙海晨 (2024-06-06 01:44):
#paper Sun Q, Zhang Y, Wang S, Yang F, Cai H, Xing Y, Zhou L, Chen S, Wang Y. LncRNA HOTAIR promotes α-synuclein aggregation and apoptosis of SH-SY5Y cells by regulating miR-221-3p in Parkinson's disease. Exp Cell Res. 2022 Aug 1;417(1):113132. doi: 10.1016/j.yexcr.2022.113132. Epub 2022 Apr 6. PMID: 35398161. 帕金森病 (Parkinson's disease,PD) 是一种常见的神经退行性疾病,其特征是神经元逐渐丢失。PD 的发病机制与细胞凋亡、炎症、氧化应激和 α-突触核蛋白聚集体的积累密切相关。本研究旨在探讨长链非编码RNA(long non-coding RNA ,lncRNA)HOX转录本反义RNA(HOX transcript antisense RNA,HOTAIR)在PD中的作用及其机制,文章研究检测了1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride,MPTP)处理的小鼠脑组织中HOTAIR、miR-221-3p和α-突触核蛋白的表达水平,探讨了HOTAIR对MPP +处理的SH-SY5Y细胞活力、凋亡、炎症和氧化应激的影响,并研究了HOTAIR/miR-221-3p/α-突触核蛋白的ceRNA调控网络。文章的研究结果显示,1、在 PD 模型中,HOTAIR 表达水平较高,而 miR-221-3p 表达水平较低。2、HOTAIR 敲低降低了 MPP+ 的神经毒性。3、HOTAIR降低了miR-221-3p的表达。4、α-突触核蛋白是 miR-221-3p 的靶基因。5、抑制 miR-221-3p 可逆转HOTAIR 敲低的神经保护作用。
Abstract:
Parkinson's disease (PD) is a common neurodegenerative disease. Here, the purpose of the study was to explore the function of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in … >>>
Parkinson's disease (PD) is a common neurodegenerative disease. Here, the purpose of the study was to explore the function of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in PD and its underlying mechanism. An in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mouse model of PD was generated and the SH-SY5Y cells were treated with MPP to induce neuronal damage in vitro. Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot were used to detect the expression of HOTAIR, miR-221-3p, α-synuclein and apoptosis-related genes. MTT, flow cytometry and TUNEL assay was used to detect cell viability and apoptosis, respectively. The levels of inflammatory cytokines TNF-α,IL-1β and IL-6 were detected by ELISA assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) were determined using the appropriate assay kits. The interactions between miR-221-3p and HOTAIR or α-synuclein were determined by dual luciferase assay and RNA binding protein immunoprecipitation (RIP). Co-localization of HOTAIR and miR-221-3p was also proved by immunofluorescence staining. The results showed that HOTAIR was highly expressed, while miR-221-3p expression was decreased in PD model in vivo and in vitro. In SH-SY5Y cells treated with MPP, the knockdown of HOTAIR increased cell viability and reduced cell apoptosis, the secretion of inflammatory cytokines and oxidative stress reaction, while HOTAIR overexpression led to opposite effects. Furthermore, HOTAIR sponged miR-221-3p which directly targeted α-synuclein and thus regulated the expression of α-synuclein. Meanwhile, inhibiting miR-221-3p could partially reverse the neuroprotective effects of HOTAIR knockdown. In conclusion, HOTAIR attenuated the injury of SH-SY5Y cells induced by MPP via miR-221-3p/α-synuclein axis, suggesting the potential therapeutic value of HOTAIR in PD. <<<
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林海onrush (2024-06-01 00:00):
#paper, QNLP in Practice: Running Compositional Models of Meaning on a Quantum Computer, https://doi.org/10.1613/jair.1.14329,关于在量子硬件上设计和实现自然语言处理(NLP)模型的研究.量子自然语言处理(QNLP)旨在开发专门为在量子硬件上运行的NLP模型。本文展示了在中等规模噪声量子计算机(NISQ)上运行的首批NLP实验,处理超过100个句子的数据集。研究的目标不是展示量子对经典NLP任务的优势,而是探索在量子硬件上运行NLP模型的过程,并为AI和NLP研究社区提供详细说明。研究发现所有模型在模拟和实际量子硬件运行中均能平稳收敛,且结果符合预期。实验结果还显示了模型的句法敏感度与任务之间的关联,例如,在某些任务中仅需简单的单词检查即可正确分类,而在另一些任务中,句法结构的重要性则更高。研究发现所有模型在模拟和实际量子硬件运行中均能平稳收敛,且结果符合预期。实验结果还显示了模型的句法敏感度与任务之间的关联,例如,在某些任务中仅需简单的单词检查即可正确分类,而在另一些任务中,句法结构的重要性则更高。
Abstract:
Quantum Natural Language Processing (QNLP) deals with the design and implementation of NLP models intended to be run on quantum hardware. In this paper, we present results on the first … >>>
Quantum Natural Language Processing (QNLP) deals with the design and implementation of NLP models intended to be run on quantum hardware. In this paper, we present results on the first NLP experiments conducted on Noisy Intermediate-Scale Quantum (NISQ) computers for datasets of size greater than 100 sentences. Exploiting the formal similarity of the compositional model of meaning by Coecke, Sadrzadeh, and Clark (2010) with quantum theory, we create representations for sentences that have a natural mapping to quantum circuits. We use these representations to implement and successfully train NLP models that solve simple sentence classification tasks on quantum hardware. We conduct quantum simulations that compare the syntax-sensitive model of Coecke et al. with two baselines that use less or no syntax; specifically, we implement the quantum analogues of a “bag-of-words” model, where syntax is not taken into account at all, and of a word-sequence model, where only word order is respected. We demonstrate that all models converge smoothly both in simulations and when run on quantum hardware, and that the results are the expected ones based on the nature of the tasks and the datasets used. Another important goal of this paper is to describe in a way accessible to AI and NLP researchers the main principles, process and challenges of experiments on quantum hardware. Our aim in doing this is to take the first small steps in this unexplored research territory and pave the way for practical Quantum Natural Language Processing. <<<
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半面阳光 (2024-05-31 23:44):
#paper DOI:https://doi.org/10.1016/j.gim.2023.100879, Genetic in Medicine, 2023, Performance of prenatal cfDNA screening for sex chromosomes. 这篇文章的主要研究目的是评估和确认游离DNA (cfDNA) 筛查在未选择的产科人群中检测性染色体非整倍体 (SCAs) 的性能。采用的方法是基于SNP的实验方法,检测的性染色体异常包括monosomy X (MX) 和三种 sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY)。共有 17,538 例符合纳入标准。cfDNA 对 MX、SCT 和胎儿性别的性能分别在 17,297、10,333 和 14,486 个妊娠中进行了评估。cfDNA 对 MX 的敏感性、特异性和阳性预测值 (PPV) 分别为 83.3%、99.9% 和 22.7%;对 SCTs 的敏感性、特异性和阳性预测值分别为 70.4%、99.9% 和 82.6%。cfDNA 对胎儿性别预测的准确率为 100%。得出的结论是cfDNA 对 SCAs 的筛查性能与其他研究报告的结果相当。SCTs 的 PPV 与常染色体三体相似,而 MX 的 PPV 明显较低。在整倍体妊娠中,cfDNA 和产后遗传筛查的胎儿性别没有不一致。这些数据将有助于解释和咨询 cfDNA 性染色体结果。
295.
符毓 (2024-05-31 23:30):
#paper doi:10.1109/TIA.2002.805572 IEEE Transactions on Industry Applications, 2002, Molecular structure of nucleic acids; A comparison between the axial flux and the radial flux structures for PM synchronous motors. 本文对比了两个外部定子一个内部转子的轴向磁通电机和一个外定子一个内转子的径向磁通电机,在电机总体积、单位损耗表面的损耗和气隙磁通密度保持不变的情况下,比较了两种电机结构的电磁转矩和转矩密度。证明当轴向长度短并且极数高的情况下,轴向磁通电机有优势
296.
muton (2024-05-31 23:28):
#paper DOI: 10.1038/s41467-017-02722-7 Similar neural responses predict friendship 一个很有意思的研究,当我们处在群体当中时,我们有很明显的同质性趋向,另外个体也更倾向于和与自己更相似的人交朋友。那么朋友之间的相似性是否反映了我们在感知、解释和应对世界方面的更深层次的相似性?作者为了测试社交网络相似性与心理反应相似性的关系,使用功能性磁共振成像来扫描受试者在自由观看自然主义电影时的大脑。结果发现,朋友之间观看视听电影时的神经反应非常相似,并且在现实世界的社交网络中,这种相似性随着距离的增加而降低。这表明你和你的朋友越像你们在面对同一个事物的神经相似性可能也越高。
IF:14.700Q1 Nature communications, 2018-01-30. DOI: 10.1038/s41467-017-02722-7 PMID: 29382820
Abstract:
Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among … >>>
Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship, and more generally, social network proximity, is associated with increased similarity of real-time mental responding, we used functional magnetic resonance imaging to scan subjects' brains during free viewing of naturalistic movies. Here we show evidence for neural homophily: neural responses when viewing audiovisual movies are exceptionally similar among friends, and that similarity decreases with increasing distance in a real-world social network. These results suggest that we are exceptionally similar to our friends in how we perceive and respond to the world around us, which has implications for interpersonal influence and attraction. <<<
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297.
孤舟蓑笠翁 (2024-05-31 22:29):
#paper doi: 10.1038/s41587-021-01033-z. Differential abundance testing on single-cell data using k-nearest neighbor graphs. 这个研究跳出了对细胞分群的框架,而是从一个细胞的邻居入手,比较组间的细胞比例差异
IF:33.100Q1 Nature biotechnology, 2022-02. DOI: 10.1038/s41587-021-01033-z PMID: 34594043 PMCID:PMC7617075
Abstract:
Current computational workflows for comparative analyses of single-cell datasets typically use discrete clusters as input when testing for differential abundance among experimental conditions. However, clusters do not always provide the … >>>
Current computational workflows for comparative analyses of single-cell datasets typically use discrete clusters as input when testing for differential abundance among experimental conditions. However, clusters do not always provide the appropriate resolution and cannot capture continuous trajectories. Here we present Milo, a scalable statistical framework that performs differential abundance testing by assigning cells to partially overlapping neighborhoods on a k-nearest neighbor graph. Using simulations and single-cell RNA sequencing (scRNA-seq) data, we show that Milo can identify perturbations that are obscured by discretizing cells into clusters, that it maintains false discovery rate control across batch effects and that it outperforms alternative differential abundance testing strategies. Milo identifies the decline of a fate-biased epithelial precursor in the aging mouse thymus and identifies perturbations to multiple lineages in human cirrhotic liver. As Milo is based on a cell-cell similarity structure, it might also be applicable to single-cell data other than scRNA-seq. Milo is provided as an open-source R software package at https://github.com/MarioniLab/miloR . <<<
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298.
白鸟 (2024-05-31 22:17):
#paper doi:10.1038/s41467-024-46625-w Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex 文章是伤性脑损伤病理机制研究,处理小鼠被刺穿大脑灰质,3天后,进行脑部切片空转,皮层出现刺伤核心区域,常规思路是分析簇VI中上调的基因,进行富集通路分析;文章一个亮点是空间梯度分析,刺穿部位损伤引起的周围区域异质性的基因表达。文章作者提出一些观点,湿实验验证等。 我比较关注的一个分析点是,脑区空间细胞类型的注释;这个目前技术比较难实现,除非原位空转技术;一般策略是空转+单细胞联用,去卷积解析每个spot的细胞类型;目前同类算法也很多,但是受匹配数据的影响,空间注释的结果不敢云云,或者说这个预测结论很多不够牢靠。文章中也同样需要分析损伤脑区的细胞类型,针对核心损伤部位的细胞进行单细胞测序,通过Tangram算法预测空间位置信息,这个预测分析不属于重要结论。我粗浅地认为,空转的细胞类型注释,唯一能把握的是,在具体空间位置上基因的表达。
IF:14.700Q1 Nature communications, 2024-Apr-03. DOI: 10.1038/s41467-024-46625-w PMID: 38570482
Abstract:
Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the … >>>
Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature. Interestingly, distinct glial cells share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreases the reactivity state of glial cells associated with poor regeneration. The functional relevance of the discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury. <<<
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299.
庞庞 (2024-05-31 21:55):
#paper doi:https://doi.org/10.1038/s41593-023-01259-x Molecular and network-level mechanisms explaining individual differences in autism spectrum disorder 该论文基于ASD患者功能连接和症状的相关情况,将ASD患者分为了三个亚型,并进一步探究了亚型间脑和基因的差异情况。对我而言其在CCA时做的特征筛选、模型验证等比较充分,且基因的部分还用brainspan数据集做了验证,可以参考。
IF:21.200Q1 Nature neuroscience, 2023-04. DOI: 10.1038/s41593-023-01259-x PMID: 36894656
Abstract:
The mechanisms underlying phenotypic heterogeneity in autism spectrum disorder (ASD) are not well understood. Using a large neuroimaging dataset, we identified three latent dimensions of functional brain network connectivity that … >>>
The mechanisms underlying phenotypic heterogeneity in autism spectrum disorder (ASD) are not well understood. Using a large neuroimaging dataset, we identified three latent dimensions of functional brain network connectivity that predicted individual differences in ASD behaviors and were stable in cross-validation. Clustering along these three dimensions revealed four reproducible ASD subgroups with distinct functional connectivity alterations in ASD-related networks and clinical symptom profiles that were reproducible in an independent sample. By integrating neuroimaging data with normative gene expression data from two independent transcriptomic atlases, we found that within each subgroup, ASD-related functional connectivity was explained by regional differences in the expression of distinct ASD-related gene sets. These gene sets were differentially associated with distinct molecular signaling pathways involving immune and synapse function, G-protein-coupled receptor signaling, protein synthesis and other processes. Collectively, our findings delineate atypical connectivity patterns underlying different forms of ASD that implicate distinct molecular signaling mechanisms. <<<
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300.
朵朵 (2024-05-31 21:47):
#paper 史晓宇,阮琳燕,何丽.他们为什么不上学?中学生拒绝上学影响因素的质性研究[J].社区心理学研究,2023,16(02):193-210. 国内有学者研究发现, 广州市中小学生拒学行为检出率为22. 5%,且拒学行为的检出率随年龄增长呈上升趋势, 小学阶段处于较低水平(4. 5%), 进入中学阶段陡升(24. 6%), 整个初中阶段约1/3 的学生有拒学行为, 到高中阶段, 拒学行为的检出率高达37. 6%。 论文采用质性研究取向的个案研究法,选取了北京市7名拒学中学生及其父母进行半结构式深度访谈。结果显示,在个人层面,主要是人际敏感、完美主义的鲜明特质;在学校层面,包括残酷的竞争与学业压力、高压高控的管理风格、面临危机的师生关系、倍感受伤的同伴群体、返校复学的重重障碍;在家庭层面,包括矛盾重重的父母关系、愈演愈烈的亲子冲突、日积月累的负面情绪、纠结复杂的二胎家庭、混乱失调的家庭功能;利弊难辨的新事物,包括网络与手机、电竞游戏、偶像练习生;精神医学层面,包括抑郁、焦虑状态。这些因素相互影响,最终导致了中学生拒学行为。 可惜的是,本论文分析比较浅,只是指出“中学生拒学行为的发生反映了个体的不适当性及社会系统的失衡,是学生个人、家庭、学校和社会因素相互作用的结果”,没有更深刻的洞见。
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