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641.
张浩彬
(2023-04-28 13:45):
#paper An Empirical Evaluation of Generic Convolutional and Recurrent Networks for Sequence Modeling DOI:arXiv:1803.01271 .
最近密集地做时序问题的分享,认真看了一下TCN的原文.除了RNN那一套,TCN还是用得比较多。为了在不增加太多层的情况下实现大的感受野,通过空洞卷积来实现,并通过padding和裁剪的方式避免了数据泄露问题。一个TCN块有两个空洞因果卷积,激活层,norm层以及一个残差链接组成。实验证明了TCN的超参数相对不敏感,但卷积核大小k是个关键,另外drop out 和梯度裁剪也有较大的帮助。
arXiv,
2018.
DOI: 10.48550/arXiv.1803.01271
Abstract:
For most deep learning practitioners, sequence modeling is synonymous with recurrent networks. Yet recent results indicate that convolutional architectures can outperform recurrent networks on tasks such as audio synthesis and …
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For most deep learning practitioners, sequence modeling is synonymous with recurrent networks. Yet recent results indicate that convolutional architectures can outperform recurrent networks on tasks such as audio synthesis and machine translation. Given a new sequence modeling task or dataset, which architecture should one use? We conduct a systematic evaluation of generic convolutional and recurrent architectures for sequence modeling. The models are evaluated across a broad range of standard tasks that are commonly used to benchmark recurrent networks. Our results indicate that a simple convolutional architecture outperforms canonical recurrent networks such as LSTMs across a diverse range of tasks and datasets, while demonstrating longer effective memory. We conclude that the common association between sequence modeling and recurrent networks should be reconsidered, and convolutional networks should be regarded as a natural starting point for sequence modeling tasks. To assist related work, we have made code available at this http URL .
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642.
LXJ
(2023-04-28 11:33):
#paper RhoB affects colitis through modulating cell signaling and intestinal microbiome.Microbiome, 2022 Sep 16;10(1). DOI:10.1186/s40168-022-01347-3. 背景:炎症性肠病(IBD)的发病机制是多因素的,IBD的诊断和治疗策略仍有待制定。RhoB调节多种细胞功能;然而,它在结肠炎中的作用尚未被探索。
结果:本文中研究者发现溃疡性结肠炎(UC)患者和DSS诱导的结肠炎小鼠的结肠组织中RhoB显著增加。与野生型小鼠相比,RhoB和RhoB小鼠发生了较轻的DSS诱导的结肠炎,杯状细胞数量和IEC增殖增加。RhoB降低通过抑制Wnt信号通路和激活p38 MAPK信号通路促进杯状细胞分化和上皮再生。此外,在RhoB和RhoB小鼠的肠道微生物组中检测到SCFA产生菌和SCFA浓度增加,并且还观察到SCFA受体表达上调。
结论:总之,较高水平的RhoB与UC有关,UC也通过调节细胞信号传导和改变肠道细菌组成和代谢产物来促进UC的发展。这些观察结果表明,RhoB具有作为UC的生物标志物和治疗靶点的潜力。
Abstract:
BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in …
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BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in colitis is unexplored.RESULTS: Here, we found RhoB was dramatically increased in colon tissues of ulcerative colitis (UC) patients and mice with DSS-induced colitis. Compared with wild type mice, RhoB+/- and RhoB-/- mice developed milder DSS-induced colitis and increased goblet cell numbers and IEC proliferation. Decreased RhoB promoted goblet cell differentiation and epithelial regeneration through inhibiting Wnt signaling pathway and activating p38 MAPK signaling pathway. Moreover, increased SCFA-producing bacteria and SCFA concentrations were detected in intestinal microbiome of both RhoB+/- and RhoB-/- mice and upregulated SCFA receptor expression was also observed.CONCLUSIONS: Taken together, a higher level of RhoB is associated with UC, which also contributes to UC development through modulating cell signaling and altering intestinal bacterial composition and metabolites. These observations suggest that RhoB has potential as a biomarker and a treatment target for UC. Video Abstract.
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643.
徐炳祥
(2023-04-24 15:24):
#paper doi: 10.1371/journal.pgen.1009325,PLOS GENETICS, 2021, Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity。早年的研究表明,运动负荷后肌纤维DNA甲基化水平发生了明显改变,然而二者之间是否存在因果关系仍未被深入研究,该研究以小鼠比目鱼肌为实验材料,研究在肌纤维特异性DNMT3A敲除后运动负荷引起的DNA甲基化、运动负荷诱导的基因表达谱重塑和运动负荷诱导后的表型变化。结果显示DNMT3A敲除诱导的全基因组去甲基化与其余诸项均无显著关联,因而认为DNA甲基化图谱的重塑仅是运动负荷诱导的基因表达重编程过程的副产品。该研究的一个明显缺陷是DNMT3A的敲除效率和由此诱导的全基因组去甲基化幅度均不足。该研究提供了运动负荷调控DNA甲基化图谱的有益信息,同时提供了合理报告阴性结果的范例。
Abstract:
In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may …
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In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely.
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644.
James
(2023-04-21 10:41):
#paper Ali Madani, Ben Krause, Eric R Greene, Subu Subramanian, Benjamin P Mohr, James M Holton, Jose Luis Olmos Jr, Caiming Xiong, Zachary Z Sun, Richard Socher, James S Fraser, Nikhil Naik Large language models generate functional protein sequences across diverse families PMID: 36702895 DOI: 10.1038/s41587-022-01618-2。 文章通过对超过1万9千个家族的2.8亿条蛋白序列进行训练从而构建 和LLM类似的深度学习模型 ProGen。其可以进一步微调到精选的序列和标签,以提高来自具有足够同源样本的家族的蛋白质的可控生成性能。针对五个不同的溶菌酶家族进行微调的人工蛋白质显示出与天然溶菌酶相似的催化效率,且与天然蛋白质的序列同一性只有 31.4%。就在论文登上Nature Biotechnology的同一天,由论文第一作者Ali Madani创办的公司Profluent Bio宣布获得由Insight Partners领投的900万美元种子轮融资。该笔融资的将用于在加利福尼亚州伯克利建立一个湿实验室,使Profluent能够在通过实验方法产生的数据与其AI系统之间创建一个紧密的反馈循环,为设计任何蛋白质提供强大的验证,并不断改进他们的AI。
Abstract:
Deep-learning language models have shown promise in various biotechnological applications, including protein design and engineering. Here we describe ProGen, a language model that can generate protein sequences with a predictable …
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Deep-learning language models have shown promise in various biotechnological applications, including protein design and engineering. Here we describe ProGen, a language model that can generate protein sequences with a predictable function across large protein families, akin to generating grammatically and semantically correct natural language sentences on diverse topics. The model was trained on 280 million protein sequences from >19,000 families and is augmented with control tags specifying protein properties. ProGen can be further fine-tuned to curated sequences and tags to improve controllable generation performance of proteins from families with sufficient homologous samples. Artificial proteins fine-tuned to five distinct lysozyme families showed similar catalytic efficiencies as natural lysozymes, with sequence identity to natural proteins as low as 31.4%. ProGen is readily adapted to diverse protein families, as we demonstrate with chorismate mutase and malate dehydrogenase.
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645.
惊鸿
(2023-04-19 15:35):
#paper Pub Date : 2019-01-23
DOI : 10.1038/s41564-018-0355-8
Harnessing undomesticated life
在实验室中只能对细菌进行细微的培养和工程改造,这限制了我们在恶劣环境中部署细菌或使用细菌生产重要化合物的能力。最近的工作通过开发新的方法来表征和工程化各种未驯化的细菌物种,从而打开了这一领域。这些技术可用于环境改造,为人类以后殖民外太空有极大的帮助
Abstract:
No abstract available.
646.
姗姗来迟
(2023-04-19 13:44):
#paper arXiv:2103.00020 Learning Transferable Visual Models From Natural Language Supervision
前天拜读了CLIP论文并去了解了一下论文中提到的prompt
拜读笔记见博文:CLIP论文拜读及理解
链接:https://blog.csdn.net/weixin_44845357/article/details/130206779
arXiv,
2021.
DOI: 10.48550/arXiv.2103.00020
Abstract:
State-of-the-art computer vision systems are trained to predict a fixed set of predetermined object categories. This restricted form of supervision limits their generality and usability since additional labeled data is …
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State-of-the-art computer vision systems are trained to predict a fixed set of predetermined object categories. This restricted form of supervision limits their generality and usability since additional labeled data is needed to specify any other visual concept. Learning directly from raw text about images is a promising alternative which leverages a much broader source of supervision. We demonstrate that the simple pre-training task of predicting which caption goes with which image is an efficient and scalable way to learn SOTA image representations from scratch on a dataset of 400 million (image, text) pairs collected from the internet. After pre-training, natural language is used to reference learned visual concepts (or describe new ones) enabling zero-shot transfer of the model to downstream tasks. We study the performance of this approach by benchmarking on over 30 different existing computer vision datasets, spanning tasks such as OCR, action recognition in videos, geo-localization, and many types of fine-grained object classification. The model transfers non-trivially to most tasks and is often competitive with a fully supervised baseline without the need for any dataset specific training. For instance, we match the accuracy of the original ResNet-50 on ImageNet zero-shot without needing to use any of the 1.28 million training examples it was trained on. We release our code and pre-trained model weights at this https URL.
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647.
张德祥
(2023-04-16 11:20):
#paper https://doi.org/10.48550/arXiv.2302.10051 一种用于理解神经计算算法基础的既定规范方法是从原则计算目 标中导出在线算法, 并评估它们与解剖学和生理学观察的兼容性。
相似性匹配目标已成为成功导出在线算法的起点, 这些算法映射到具有点神经元和 Hebbian/anti‐Hebbian 可塑性的神经网络 (NN)。这些神经网络模型解释了许多解剖学和生理学观察; 然而, 这些目 标的计算能力有限, 并且派生的 NN 无法解释在整个大脑中普遍存在的多隔室神经元结构和非赫布形式的可塑性。在本文中, 我们回顾并统一了相似性匹配方法的最新扩展, 以解决更复杂的目 标, 包括范围广泛的无监督和自 监督学习任务, 这些任务可以表述为广义特征值问题或非负矩阵分解问题。有趣的是, 源自这些目 标的在线算法自 然地映射到具有多隔室神经元和局部非赫布学习规则的神经网络。
因此, 这种相似性匹配方法的统一扩展提供了一个规范框架, 有助于理解整个大脑中发现的多区室神经元结构和非赫布可塑性。
arXiv,
2023.
DOI: 10.48550/arXiv.2302.10051
Abstract:
An established normative approach for understanding the algorithmic basis of neural computation is to derive online algorithms from principled computational objectives and evaluate their compatibility with anatomical and physiological observations. …
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An established normative approach for understanding the algorithmic basis of neural computation is to derive online algorithms from principled computational objectives and evaluate their compatibility with anatomical and physiological observations. Similarity matching objectives have served as successful starting points for deriving online algorithms that map onto neural networks (NNs) with point neurons and Hebbian/anti-Hebbian plasticity. These NN models account for many anatomical and physiological observations; however, the objectives have limited computational power and the derived NNs do not explain multi-compartmental neuronal structures and non-Hebbian forms of plasticity that are prevalent throughout the brain. In this article, we review and unify recent extensions of the similarity matching approach to address more complex objectives, including a broad range of unsupervised and self-supervised learning tasks that can be formulated as generalized eigenvalue problems or nonnegative matrix factorization problems. Interestingly, the online algorithms derived from these objectives naturally map onto NNs with multi-compartmental neurons and local, non-Hebbian learning rules. Therefore, this unified extension of the similarity matching approach provides a normative framework that facilitates understanding the multi-compartmental neuronal structures and non-Hebbian plasticity found throughout the brain.
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648.
龙海晨
(2023-04-10 13:25):
#paper Toama W, Wiederin J, Shanley R, Jewett P, Gu C, Shenoy C, Nijjar PS, Blaes AH. Impact of pectoralis muscle loss on cardiac outcome and survival in Cancer patients who received anthracycline based chemotherapy: retrospective study. BMC Cancer. 2022 Jul 13;22(1):763. doi: 10.1186/s12885-022-09882-w. PMID: 35831837; PMCID: PMC9281070. 文章回顾研究了几种癌症患者用蒽环类药物化疗后胸肌质量指数(pectoralis muscle mass index,PMI)与总体死亡率,主要心脏事件(Major Adverse Cardiovascular Events,MACE)生存率间的关系。(这里给大家解释几个专业名词MACE通俗讲解就是与心脏相关的不好的事情,例如,1,心脏原因引起的死亡;2,发生非致命的心肌梗死;3;发生非致命的心血管事件。具体点来说,日常遇到的,复发心绞痛、急性心肌梗死、严重心律失常、心力衰竭、冠心病死亡,心血管疾病事件,心衰,缺血性心血管事件,心源性死亡。PMI是计算胸肌的一个指标,有点类似于我们日常生活中的BMI,PMI:胸大肌面积 [cm 2 ]/身高2 [m 2 ])文章对474名癌症患者进行了回顾性分析,发现,接受蒽环类药物治疗的患者治疗前胸肌指数越高,发生 MACE 的风险越低。认为对化疗前检测PMI,尤其是对肌肉减少症患者化疗前进行干预预防能有效减少患者的MACE风险。
Abstract:
INTRODUCTION: The impact of pectoralis muscle mass index (PMI) on cardiac events is not well studied in cancer patients, especially in those who have received chemotherapy with high potential cardiac …
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INTRODUCTION: The impact of pectoralis muscle mass index (PMI) on cardiac events is not well studied in cancer patients, especially in those who have received chemotherapy with high potential cardiac toxicity such as anthracyclines.METHODS: Individuals aged ≥18 years with a diagnosis of breast cancer, sarcoma, or lymphoma who received anthracycline-based chemotherapy at the University of Minnesota MHealth Fairview between 2009 and 2014. Eligible patients had to have two CT scans: a baseline CT scan within 6 months prior to chemotherapy and a follow-up CT scan within 2 years after treatment. The PMI was calculated as the right pectoralis muscle area indexed to height squared. Multivariable linear regression was used to analyze factors associated with PMI at follow-up, overall mortality, and major cardiac events (MACE).RESULTS: A total of 474 patients (breast cancer 192; lymphoma 184; sarcoma 98) participated with a median age of 61 years at the time of baseline CT scan; 161 (34%) were male. Almost all patients received anthracyclines except 12% who received trastuzumab only. The median baseline PMI was 5.8 cm2/m2 (4.9, 7.7) which decreased 10.5% after chemotherapy, to 5.2 cm2/m2 (4.4, 6.4). Baseline PMI was not significantly associated with OS, but we detected lower risks of MACE with larger PMI at baseline. Greater baseline PMI was associated with greater follow-up PMI, but also with greater relative PMI loss. Female gender, older age, and history of smoking were also associated with greater PMI losses.CONCLUSION: Greater pre-treatment pectoralis muscle index in patients treated with anthracyclines have a lower risk of MACE. Early identification of sarcopenia using PMI could trigger proactive engagement for intervention and risk-stratified therapies.
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649.
DeDe宝
(2023-04-10 11:47):
#paper doi:/10.1371/journal.pone.0000943.Causal Inference in Multisensory Perception,2007,Plos One(发表在Plos One,但是引用高)
神经系统不断地将来自不同感觉方式的不确定信息组合成对感觉刺激原因的综合理解。这些信息可能有相同的来源,也可能来自不同的来源,因此,线索的组合必须根据线索的因果关系。多模式感知整合的方法之一是线索整合概率模型,线索整合概率模型的基础是假定原因是统一的,但是后来的实验发现,当视觉和听觉刺激差异很大时,这种整合就会失效。信息之间的差异称为disparity(分离度)。当两个线索之间的disparity(分离度)增大,那么线索A对于另一个线索B的影响就会减小,反之亦然。disparity(分离度)的存在说明强制融合(无条件假定原因统一)是不成立的,因此还需要对线索之间的因果关系进行推断,需要在模型中增加一个检验交互性的先验(一个联合先验分布),用来分析两个线索同源的可能性高,还是不同源的可能性高。本研究提出了一个因果推断模型,该模型准确地预测了人类受试者在两个听觉-视觉定位任务中对线索的非线性整合。结果表明,人类确实可以有效地推断因果结构以及线索源的位置。推断因果结构的能力不仅限于有意识的、高层次的认知;它也在感知中不断地、毫不费力地进行。
Abstract:
Perceptual events derive their significance to an animal from their meaning about the world, that is from the information they carry about their causes. The brain should thus be able …
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Perceptual events derive their significance to an animal from their meaning about the world, that is from the information they carry about their causes. The brain should thus be able to efficiently infer the causes underlying our sensory events. Here we use multisensory cue combination to study causal inference in perception. We formulate an ideal-observer model that infers whether two sensory cues originate from the same location and that also estimates their location(s). This model accurately predicts the nonlinear integration of cues by human subjects in two auditory-visual localization tasks. The results show that indeed humans can efficiently infer the causal structure as well as the location of causes. By combining insights from the study of causal inference with the ideal-observer approach to sensory cue combination, we show that the capacity to infer causal structure is not limited to conscious, high-level cognition; it is also performed continually and effortlessly in perception.
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650.
笑对人生
(2023-03-31 23:57):
#paper doi: 10.1016/j.cell.2018.03.027.Chen H, et al. A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples. Cell. 2018 Apr 5;173(2):386-399.e12.
增强子(enhancer)通常位于结构基因的附近,是一类非编码DNA调节元件,在癌症的发展过程中起到越来越重要的作用。本研究利用TCGA数据库33癌种,总共8928肿瘤患者的RNA-seq数据,从全基因组范围识别和鉴定出大量表达的增强子。通过与正常组织进行比较,发现大多数癌种的增强子处在激活状态,且与非整倍体改变正相关,但与突变负荷无关,由此提出增强子与基因互作的染色体状态假说。为了建立因果关系的增强子-基因调控网络模型,作者通过整合eQTL分析、mRNA共表达分析以及Hi-C数据分析的结果,最终发现65个增强子-基因互作对。这些互作对经过CGC注释,总共包含22个原癌基因和8个肿瘤抑制基因。文章的最后,作者还通过CRISPR/Cas9 RNAs技术证实了存在于PD-L1基因上游140kb的一个增强子。
Abstract:
The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number …
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The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on "chromatin-state" to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.
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651.
彬
(2023-03-31 23:30):
#paper 2023-Structural changes induced by pasteurisation and/or high-pressure treatment of skim caprine milk。https://doi.org/10.1016/j.idairyj.2022.105528。该研究结果表明脱脂山羊乳的巴氏杀菌和高压(HP)组合(PHP)过程可以改变蛋白质的二级结构,导致表面疏水性增加。HP处理前的巴氏杀菌降低了α-螺旋结构含量,同时增加了β-折叠结构含量,这与脱脂山羊乳样品表面疏水性和固有荧光的变化有关。对于PHP和HP处理组样品,随着压力水平的增加和处理时间的延长,α-螺旋和β-转角结构含量降低,而β-折叠和无规卷曲结构含量增加。PHP处理可作为乳制品行业的一种良好替代技术,以提高脱脂山羊乳的功能特性。
Abstract:
The effects of pasteurisation, high-pressure (HP), and a combination of pasteurisation and high-pressure (PHP) on the physicochemical properties and protein structure of caprine skim milk was investigated. Samples treated by …
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The effects of pasteurisation, high-pressure (HP), and a combination of pasteurisation and high-pressure (PHP) on the physicochemical properties and protein structure of caprine skim milk was investigated. Samples treated by PHP generally had a higher pH, whey protein denaturation, surface hydrophobicity, and intrinsic fluorescence than those treated only with heat or pressure. In contrast, the size of skim milk casein micelles decreased significantly with an increase in pressure level and time; however, the effect was less marked when heat and pressure treatments were combined. For the PHP and HP samples, as the level and time of pressure increased, the α-helix and β-turn content reduced, whereas β-sheet and random coil were induced. Thus, PHP treatment could be used as a good alternative technology in the dairy industry to promote the functional properties of skim caprine milk.
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652.
林海onrush
(2023-03-31 23:17):
#paper, BloombergGPT: A Large Language Model for Finance, doi:10.48550/arXiv.2303.17564, ChatGPT引爆的AI热潮也“烧到了”金融圈,彭博社重磅发布为金融界打造的大型语言模型(LLM)——BloombergGPT。3月30日,根据彭博社最新发布的报告显示,其构建迄今为止最大的特定领域数据集,并训练了专门用于金融领域的LLM,开发了拥有500亿参数的语言模型——BloombergGPT。报告显示,该模型依托彭博社的大量金融数据源,构建了一个3630亿个标签的数据集,支持金融行业内的各类任务。该模型在金融任务上的表现远超过现有模型,且在通用场景上的表现与现有模型也能一较高下。报告指出,从测试来看,BloombergGPT在五项任务中的四项(ConvFinQA,FiQA SA,FPB和Headline)表现最佳,在NER(Named Entity Recognition)中排名第二。因此,BloombergGPT有其优势性。
arXiv,
2023.
DOI: 10.48550/arXiv.2303.17564
Abstract:
The use of NLP in the realm of financial technology is broad and complex, with applications ranging from sentiment analysis and named entity recognition to question answering. Large Language Models …
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The use of NLP in the realm of financial technology is broad and complex, with applications ranging from sentiment analysis and named entity recognition to question answering. Large Language Models (LLMs) have been shown to be effective on a variety of tasks; however, no LLM specialized for the financial domain has been reported in literature. In this work, we present BloombergGPT, a 50 billion parameter language model that is trained on a wide range of financial data. We construct a 363 billion token dataset based on Bloomberg's extensive data sources, perhaps the largest domain-specific dataset yet, augmented with 345 billion tokens from general purpose datasets. We validate BloombergGPT on standard LLM benchmarks, open financial benchmarks, and a suite of internal benchmarks that most accurately reflect our intended usage. Our mixed dataset training leads to a model that outperforms existing models on financial tasks by significant margins without sacrificing performance on general LLM benchmarks. Additionally, we explain our modeling choices, training process, and evaluation methodology. As a next step, we plan to release training logs (Chronicles) detailing our experience in training BloombergGPT.
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653.
小擎子
(2023-03-31 23:05):
#paper doi:10.1136/gutjnl-2018-317178 Gut, 2019, Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer 结直肠癌的肠道真菌失调和生态改变。一般研究癌症里的微生物多是细菌,病毒和真菌的少。这篇文献主要分析了结直肠癌患者样本的真菌。真菌一般在采样中的序列占比也少,但仍有分析价值。研究分析了香港的184名CRC患者、197名腺瘤患者和204名对照受试者。分析的粪便样本,分为发现队列和验证队列。主成分分析显示结直肠癌和对照组可以分为两个簇,早期和晚期的结直肠癌也有不同的真菌群。与健康人相比,结直肠癌患者粪便内的担子菌(Basidiomycota):子囊菌(Ascomycota)的比值增加。在CRC中真菌纲马拉色纲(Malasseziomycetes)富集,Saccharomycetes和Pneumocystidomycetes减少。研究找了14种真菌标志物其丰度可以将CRC和对照组分开,AUC为0.74~0.93。研究还采用了SparCC算法做了生态学分析,与对照组相比,CRC中的真菌会有界内共存的联系,而真菌与细菌会有排斥现象。研究发现了真菌粪便标志物在诊断CRC上有潜在潜力。真菌一般分析较少,研究主要用了Kraken注释reads,并且用Jellyfish程序利用公开数据做了一个自定义数据库。
Abstract:
OBJECTIVES: Bacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in CRC.DESIGN: Faecal …
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OBJECTIVES: Bacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in CRC.DESIGN: Faecal shotgun metagenomic sequences of 184 patients with CRC, 197 patients with adenoma and 204 control subjects from Hong Kong were analysed (discovery cohort: 73 patients with CRC and 92 control subjects; validation cohort: 111 patients with CRC, 197 patients with adenoma and 112 controls from Hong Kong). CRC-associated fungal markers and ecological changes were also validated in additional independent cohorts of 90 patients with CRC, 42 patients with adenoma and 66 control subjects of published repository sequences from Germany and France. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.RESULTS: Principal component analysis revealed separate clusters for CRC and control (p<0.0001), with distinct mycobiomes in early-stage and late-stage CRC (p=0.0048). Basidiomycota:Ascomycota ratio was higher in CRC (p=0.0042), with increase in Malasseziomycetes (p<0.0001) and decrease in Saccharomycetes (p<0.0001) and Pneumocystidomycetes (p=0.0017). Abundances of 14 fungal biomarkers distinguished CRC from controls with an area under the receiver-operating characteristic curve (AUC) of 0.93 and validated AUCs of 0.82 and 0.74 in independent Chinese cohort V1 and European cohort V2, respectively. Further ecological analysis revealed higher numbers of co-occurring fungal intrakingdom and co-exclusive bacterial-fungal correlations in CRC (p<0.0001). Moreover, co-occurrence interactions between fungi and bacteria, mostly contributed by fungal Ascomycota and bacterial Proteobacteria in control, were reverted to co-exclusive interplay in CRC (p=0.00045).CONCLUSIONS: This study revealed CRC-associated mycobiome dysbiosis characterised by altered fungal composition and ecology, signifying that the gut mycobiome might play a role in CRC.
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654.
钟鸣
(2023-03-31 22:47):
#paper doi:10.1128/iai.00529-22 Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone 过去的研究中发现高血糖患者更容易发生严重的金黄色葡萄球菌感染,这是一种广泛存在于环境中且具有重要公共卫生意义的细菌。为了这种现象的原因,研究者使用小鼠作为实验动物,构建了高血糖模型,同时使用转座子测序技术对金黄色葡萄球菌随机插入突变,随后攻毒检验毒力。实验结果是得到一个基因,sodA ,编码超氧化物歧化酶 A,与该菌在高糖环境下的毒力增加有关。从技术和研究方案来说很成熟很简单,但是得到的结论很有价值且深远。但该基因如何影响金黄色葡萄球菌在特定环境下的表型,以及这种调控是否具有种属特异性、该基因是否具有未探明的功能,仍然未知。当然还需要更多的实验从不同角度验证本文的结论。
Abstract:
Hyperglycemia, or elevated blood glucose, renders individuals more prone to developing severe Staphylococcus aureus infections. S. aureus is the most common etiological agent of musculoskeletal infection, which is a common …
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Hyperglycemia, or elevated blood glucose, renders individuals more prone to developing severe Staphylococcus aureus infections. S. aureus is the most common etiological agent of musculoskeletal infection, which is a common manifestation of disease in hyperglycemic patients. However, the mechanisms by which S. aureus causes severe musculoskeletal infection during hyperglycemia are incompletely characterized. To examine the influence of hyperglycemia on S. aureus virulence during invasive infection, we used a murine model of osteomyelitis and induced hyperglycemia with streptozotocin. We discovered that hyperglycemic mice exhibited increased bacterial burdens in bone and enhanced dissemination compared to control mice. Furthermore, infected hyperglycemic mice sustained increased bone destruction relative to euglycemic controls, suggesting that hyperglycemia exacerbates infection-associated bone loss. To identify genes contributing to S. aureus pathogenesis during osteomyelitis in hyperglycemic animals relative to euglycemic controls, we used transposon sequencing (TnSeq). We identified 71 genes uniquely essential for S. aureus survival in osteomyelitis in hyperglycemic mice and another 61 mutants with compromised fitness. Among the genes essential for S. aureus survival in hyperglycemic mice was the gene encoding superoxide dismutase A (), one of two S. aureus superoxide dismutases involved in detoxifying reactive oxygen species (ROS). We determined that a mutant exhibits attenuated survival in high glucose and during osteomyelitis in hyperglycemic mice. SodA therefore plays an important role during growth in high glucose and promotes S. aureus survival in bone. Collectively, these studies demonstrate that hyperglycemia increases the severity of osteomyelitis and identify genes contributing to S. aureus survival during hyperglycemic infection.
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655.
muton
(2023-03-31 22:44):
#paper https://doi.org/10.7554/eLife.82250 Extra-hippocampal contributions to pattern separation 模式分离,或记忆中高度相似的刺激或经验由不重叠的神经组合代表的过程,通常被归结为由海马体支持的过程。然而,广泛研究的证据表明,模式分离是一个由大脑区域网络支持的多阶段过程。基于这些证据,再加上文献中的相关发现,作者提出了 "皮质-海马模式分离"(CHiPS)框架,认为参与认知控制的大脑区域在模式分离中发挥了重要作用。特别是,这些区域可能通过以下方式对模式分离做出贡献:(1)解决投射到海马的感觉区域的干扰,从而调节其皮质输入;或(2)根据任务要求直接调节海马的过程。本文创新之处是作者认为模式分离也同样受到新皮层-海马而不仅仅是海马的支持。
Abstract:
Pattern separation, or the process by which highly similar stimuli or experiences in memory are represented by non-overlapping neural ensembles, has typically been ascribed to processes supported by the hippocampus. …
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Pattern separation, or the process by which highly similar stimuli or experiences in memory are represented by non-overlapping neural ensembles, has typically been ascribed to processes supported by the hippocampus. Converging evidence from a wide range of studies, however, suggests that pattern separation is a multistage process supported by a network of brain regions. Based on this evidence, considered together with related findings from the interference resolution literature, we propose the 'cortico-hippocampal pattern separation' (CHiPS) framework, which asserts that brain regions involved in cognitive control play a significant role in pattern separation. Particularly, these regions may contribute to pattern separation by (1) resolving interference in sensory regions that project to the hippocampus, thus regulating its cortical input, or (2) directly modulating hippocampal processes in accordance with task demands. Considering recent interest in how hippocampal operations are modulated by goal states likely represented and regulated by extra-hippocampal regions, we argue that pattern separation is similarly supported by neocortical-hippocampal interactions.
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656.
Ricardo
(2023-03-31 22:43):
#paper Growth charts of brain morphometry for preschool children https://doi.org/10.1016/j.neuroimage.2022.119178 从1到6岁的大脑发育确定了广泛的功能能力,并带有神经发育障碍的早期迹象。然而,目前缺乏描述大脑形态变化和进行个性化推断的定量模型,阻碍了这一时期早期大脑非典型性的识别。通过285个样本,我们描述了神经功能正常儿童皮层厚度和皮层下体积的年龄依赖性,并构建了学龄前儿童所有大脑区域的定量生长图表。大部分脑区的皮质厚度随年龄的增加而减小,而内嗅区和海马旁区则呈现出倒u型的年龄依赖关系。与皮层厚度相比,皮层下区域的归一化体积变化趋势更为发散,有的区域增大,有的区域减小,有的区域呈倒u型变化趋势。所有大脑区域的生长曲线模型在识别大脑非典型性方面显示出效用。生长曲线的百分位数测量有助于识别发育性言语和语言障碍儿童,其准确率为0.875。该结果填补了关键发育时期脑形态测量学的知识空白,并为个性化的脑发育状态评估提供了一条途径,具有良好的敏感性。
Abstract:
Brain development from 1 to 6 years of age anchors a wide range of functional capabilities and carries early signs of neurodevelopmental disorders. However, quantitative models for depicting brain morphology …
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Brain development from 1 to 6 years of age anchors a wide range of functional capabilities and carries early signs of neurodevelopmental disorders. However, quantitative models for depicting brain morphology changes and making individualized inferences are lacking, preventing the identification of early brain atypicality during this period. With a sample size of 285, we characterized the age dependence of the cortical thickness and subcortical volume in neurologically normal children and constructed quantitative growth charts of all brain regions for preschool children. While the cortical thickness of most brain regions decreased with age, the entorhinal and parahippocampal regions displayed an inverted-U shape of age dependence. Compared to the cortical thickness, the normalized volume of subcortical regions exhibited more divergent trends, with some regions increasing, some decreasing, and some displaying inverted-U-shaped trends. The growth curve models for all brain regions demonstrated utilities in identifying brain atypicality. The percentile measures derived from the growth curves facilitate the identification of children with developmental speech and language disorders with an accuracy of 0.875 (area under the receiver operating characteristic curve: 0.943). Our results fill the knowledge gap in brain morphometrics in a critical development period and provide an avenue for individualized brain developmental status evaluation with demonstrated sensitivity. The brain growth charts are shared with the public (http://phi-group.top/resources.html).
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657.
张贝
(2023-03-31 22:30):
#paper RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science. 2019 Jun 7;364(6444):eaaw0726.doi: 10.1126/science.aaw0726. 体细胞突变是如何在正常细胞中积累的,目前尚不清楚。本文通过对来自29个正常组织的6700个样本的RNA测序数据的综合分析揭示了多个体细胞变异,表明在许多正常组织中可以发现宏观克隆。本文证实阳光照射的皮肤、食道和肺比其他测试组织有更高的突变负担,这表明环境因素可以促进体细胞嵌合。突变负担与年龄和组织特异性细胞增殖率相关,强调突变随着时间和细胞分裂数量的增加而积累。最后,作者发现正常组织中存在已知癌症基因和热点突变。本研究提供了人体组织中宏观克隆扩增的广阔视野,从而作为将克隆扩增与环境因素、衰老和疾病风险联系起来的基础
Abstract:
How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that …
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How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.
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658.
大勇
(2023-03-31 21:39):
#paper Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer. Immunity. 2022 Mar 8;55(3):527-541.e5. doi: 10.1016/j.immuni.2022.02.001. Epub 2022 Feb 28. PMID: 35231421这篇文献主要通过空间转录组的数据和计算机成像,给我们展示了肿瘤组织中三级淋巴结构的微环境细胞图谱,发现B细胞聚集区以及B细胞抗原刺激的过程。并且CXCL12的成纤维细胞可以促进B细胞的扩散和发挥抗体介导的肿瘤ADCC的作用。
Abstract:
The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of …
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The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.
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659.
小小小小小小萌
(2023-03-31 21:16):
#paper https://www.nature.com/articles/s41421-022-00416-z Dynamic 3D genome reorganization during development and metabolic stress of the porcine liver.
这篇文章运用了基因组学尤其是三维基因组学功能研究中最常用的实验技术,包括ChIP-seq,Hi-C,ATAC-seq和RNA-seq,研究了猪的肝脏在胚胎形成阶段的两个时期及猪出生后肝脏生长至2.5cm, 8cm, 10cm的基因组学变化情况。揭示了肝脏发育过程中染色质空间结构的建立以及参与转录调控的过程。同时,对成年后高脂饮食诱导肥胖组的分析表明猪的各项代谢指标和染色质层级构象在体重增加的过程中并未发生明显变化。
Abstract:
Liver development is a complex process that is regulated by a series of signaling pathways. Three-dimensional (3D) chromatin architecture plays an important role in transcriptional regulation; nonetheless, its dynamics and …
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Liver development is a complex process that is regulated by a series of signaling pathways. Three-dimensional (3D) chromatin architecture plays an important role in transcriptional regulation; nonetheless, its dynamics and role in the rapid transition of core liver functions during development and obesity-induced metabolic stress remain largely unexplored. To investigate the dynamic chromatin architecture during liver development and under metabolic stress, we generated high-resolution maps of chromatin architecture for porcine livers across six major developmental stages (from embryonic day 38 to the adult stage) and under a high-fat diet-induced obesity. The characteristically loose chromatin architecture supports a highly plastic genome organization during early liver development, which fundamentally contributes to the rapid functional transitions in the liver after birth. We reveal the multi-scale reorganization of chromatin architecture and its influence on transcriptional regulation of critical signaling processes during liver development, and show its close association with transition in hepatic functions (i.e., from hematopoiesis in the fetus to metabolism and immunity after birth). The limited changes in chromatin structure help explain the observed metabolic adaptation to excessive energy intake in pigs. These results provide a global overview of chromatin architecture dynamics associated with the transition of physiological liver functions between prenatal development and postnatal maturation, and a foundational resource that allows for future in-depth functional characterization.
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660.
AI 5.0.3
(2023-03-31 20:44):
#paper 主要内容:快速伽马震荡精准协调上下神经系统,分别从海马外内侧收集神经元信息传入海马实现在物体识别和方位判断的作用。主要结论:空间导航中快伽马震荡协调齿状回和MEC,慢伽马震荡协调齿状回和LEC,MEC和LEC的信息以伽马周期对任务进行特异性选择。A. Fernández-Ruiz et al., Science 372, eabf3119 (2021). DOI: 10.1126/science.abf3119
Abstract:
Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat …
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Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner. Gamma perturbation disrupted the learning-induced assembly organization of target neurons. Our findings imply that pathway-specific gamma oscillations route task-relevant information between distinct neuronal subpopulations in the entorhinal-hippocampal circuit. We hypothesize that interregional gamma-time-scale spike coordination is a mechanism of neuronal communication.
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