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A Comparative Study of Neutron Irradiation for Genetic Mutations: Spallation, Reactor, and Compact Neutron Source 中子辐照基因突变的比较研究:溅射、反应堆和紧凑型中子源
Pub Date : 2024-08-20 DOI: arxiv-2408.10929
May Sweet, Kenji Mishima, Masahide Harada, Keisuke Kurita, Hiroshi Iikura, Seiji Tasaki, Norio Kikuchi
Neutron beam, being electrically neutral and highly penetrating, offersunique advantages for irradiation of biological species such as plants, seeds,and microorganisms. We comprehensively investigate the potential of neutronirradiation for inducing genetic mutations using simulations of J-PARC BL10,JRR-3 TNRF, and KUANS for spallation, reactor, and compact neutron sources. Weanalyze neutron flux, energy deposition rates, and Linear Energy Transfer (LET)distributions. KUANS demonstrated the highest dose rate of 17 Gy/h,significantly surpassing BL10, due to the large solid angle by the optimalsample placement. The findings highlight KUANS's suitability for efficientgenetic mutations and neutron breeding, particularly for inducing targetedmutations in biological samples. The LET range of KUANS is concentrated in20-70 keV/{mu}m, which is potentially ideal for inducing specific geneticmutations. The importance of choosing neutron sources based on LET requirementsto maximize mutation induction efficiency is emphasized. This research showsthe potential of compact neutron sources like KUANS for effective biologicalirradiation and neutron breeding, offering a viable alternative to largerfacilities. The neutron filters used in BL10 and TNRF effectively excludedlow-energy neutrons with keeping the high LET component. The neutron capturereaction, 14N(n,p)14C, was found to be the main dose under thermalneutron-dominated conditions.
中子束是电中性的,穿透力强,在辐照植物、种子和微生物等生物物种方面具有独特的优势。我们通过模拟 J-PARC BL10、JRR-3 TNRF 和 KUANS 的溅射、反应堆和紧凑型中子源,全面研究了中子辐照诱导基因突变的潜力。我们分析了中子通量、能量沉积率和线性能量传递(LET)分布。KUANS 的剂量率最高,达到 17 Gy/h,大大超过 BL10,这得益于优化的样品放置所产生的大固着角。这些研究结果突出表明,KUANS 适用于高效基因突变和中子培育,特别是在生物样本中诱导靶向突变。KUANS 的 LET 范围集中在 20-70 keV/{/mu}m,这可能是诱导特定基因突变的理想选择。强调了根据 LET 要求选择中子源以最大限度地提高突变诱导效率的重要性。这项研究表明,像 KUANS 这样的紧凑型中子源具有进行有效生物辐照和中子育种的潜力,为大型设施提供了可行的替代方案。BL10 和 TNRF 使用的中子滤波器在保留高 LET 成分的同时,有效地排除了低能中子。研究发现,在热中子主导条件下,中子俘获反应 14N(n,p)14C 是主要剂量。
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引用次数: 0
Physical limits on chemical sensing in bounded domains 有界域中化学传感的物理限制
Pub Date : 2024-08-20 DOI: arxiv-2408.10745
Daniel R. McCusker, David K. Lubensky
Cells respond to chemical cues, and the precision with which they can sensethese cues is fundamentally limited by the stochastic nature of diffusion andligand binding. Berg and Purcell famously investigated how well a small sensorin an infinite ligand bath can determine the ligand concentration, and a numberof subsequent analyses have refined and built upon their classical estimates.Not all concentration sensing problems, however, occur in such an infinitegeometry. At different scales, subcellular sensors and cells in tissues areboth often confronted with signals whose diffusion is affected by confiningboundaries. It is thus valuable to understand how basic limits onchemosensation depend on the sensor's size and on its position in the domain inwhich ligand diffuses. Here we compute how sensor size and proximity toreflecting boundaries affect the diffusion-limited precision of chemosensationfor various geometries in one and three dimensions. We derive analyticalexpressions for the sensing limit in these geometries. Among our conclusions isthe surprising result that, in certain circumstances, smaller sensors can bemore effective than larger sensors. This effect arises from a trade-off betweenspatial averaging and time averaging that we analyze in detail. We also findthat proximity to confining boundaries can degrade a sensor's precisionsignificantly compared to the precision of the same sensor far from anyboundaries.
细胞会对化学线索做出反应,而它们感知这些线索的精确度从根本上受到扩散和配体结合随机性的限制。伯格和珀塞尔曾对无限配体浴中的小型传感器确定配体浓度的能力进行过著名的研究,随后的一些分析对他们的经典估计进行了改进和发展。在不同的尺度上,亚细胞传感器和组织中的细胞都经常面临扩散受封闭边界影响的信号。因此,了解化学感应的基本限制如何取决于传感器的大小及其在配体扩散域中的位置是非常有价值的。在这里,我们计算了传感器的尺寸和与反射边界的接近程度如何影响一维和三维各种几何形状的扩散限制化学感应精度。我们推导出了这些几何形状中传感极限的分析表达式。我们的结论中包括一个令人惊讶的结果,即在某些情况下,较小的传感器可能比较大的传感器更有效。这种效应源于空间平均和时间平均之间的权衡,我们对此进行了详细分析。我们还发现,与远离任何边界的同一传感器的精度相比,靠近限制边界会显著降低传感器的精度。
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引用次数: 0
Exploring the Thermostability of CRISPR Cas12b using Molecular Dynamics Simulations 利用分子动力学模拟探索 CRISPR Cas12b 的耐热性
Pub Date : 2024-08-20 DOI: arxiv-2408.11149
Yinhao Jia, Katelynn Horvath, Santosh R. Rananaware, Piyush K. Jain, Janani Sampath
CRISPR (clustered regularly interspaced short palindromic repeat)- baseddiagnostics are at the forefront of rapid detection platforms of infectiousdiseases. The integration of reverse transcription-loop-mediated isothermalamplification (RT-LAMP) with CRISPR-Cas protein systems has led to the creationof advanced one-pot assays. The sensitivity of these assays has been bolsteredby the utilization of a thermophilic Cas12 protein, BrCas12b, and itsengineered variant, which exhibits enhanced thermal stability and allows forbroader operation temperatures of the assay. Here, we perform all-atommolecular dynamics (MD) simulations on wild-type and mutant BrCas12b to revealthe mechanism of stabilization conferred by the mutation. High-temperaturesimulations reveal a small structural change along with greater flexibility inthe PAM-interacting domain of the mutant BrCas12b, with marginal structural andflexibility changes in the other mutated domains. Comparative essentialdynamics analysis between the wild-type and mutant BrCas12b at both ambient andelevated temperatures provides insights into the stabilizing effects of themutations. Our findings not only offer a comprehensive insight into the dynamicalterations induced by mutations but reveal important motions in BrCas12b,important for the rational design of diagnostic and therapeutic platforms ofCas12 proteins.
基于 CRISPR(簇状规则间隔短回文重复序列)的诊断技术是传染性疾病快速检测平台的前沿技术。将反转录环介导等温扩增(RT-LAMP)技术与 CRISPR-Cas 蛋白系统结合在一起,开发出了先进的一锅检测法。利用嗜热的 Cas12 蛋白 BrCas12b 及其工程变体提高了这些检测方法的灵敏度,该变体具有更高的热稳定性,允许更宽的检测操作温度。在这里,我们对野生型和突变型 BrCas12b 进行了全原子分子动力学(MD)模拟,以揭示突变所带来的稳定机制。高温模拟显示,突变体BrCas12b的PAM相互作用结构域发生了微小的结构变化和更大的灵活性,其他突变结构域的结构和灵活性变化不大。野生型和突变体BrCas12b在环境温度和高温条件下的本质动力学比较分析有助于深入了解突变的稳定作用。我们的发现不仅全面揭示了突变引起的动力学变化,而且揭示了 BrCas12b 的重要运动,这对合理设计 Cas12 蛋白的诊断和治疗平台非常重要。
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引用次数: 0
Solution landscape of reaction-diffusion systems reveals a nonlinear mechanism and spatial robustness of pattern formation 反应-扩散系统的解景观揭示了模式形成的非线性机制和空间稳健性
Pub Date : 2024-08-19 DOI: arxiv-2408.10095
Shuonan Wu, Bing Yu, Yuhai Tu, Lei Zhang
Spontaneous pattern formation in homogeneous systems is ubiquitous in nature.Although Turing demonstrated that spatial patterns can emerge inreaction-diffusion (RD) systems when the homogeneous state becomes linearlyunstable, it remains unclear whether the Turing mechanism is the only route forpattern formation. Here, we develop an efficient algorithm to systematicallymap the solution landscape to find all steady-state solutions. By applying ourmethod to generic RD models, we find that stable spatial patterns can emergevia saddle-node bifurcations before the onset of Turing instability.Furthermore, by using a generalized action in functional space based on largedeviation theory, our method is extended to evaluate stability of spatialpatterns against noise. Applying this general approach in a three-species RDmodel, we show that though formation of Turing patterns only requires twochemical species, the third species is critical for stabilizing patternsagainst strong intrinsic noise in small biochemical systems.
虽然图灵证明了当均相状态变得线性不稳定时,反应-扩散(RD)系统中会出现空间模式,但图灵机制是否是模式形成的唯一途径仍不清楚。在此,我们开发了一种高效算法,用于系统地绘制解景观图,以找到所有稳态解。通过将我们的方法应用于一般的 RD 模型,我们发现在图灵不稳定性出现之前,稳定的空间模式可以通过鞍节点分岔出现。此外,通过使用基于大偏差理论的函数空间广义作用,我们的方法被扩展用于评估空间模式对抗噪声的稳定性。我们在三物种 RD 模型中应用了这种通用方法,结果表明虽然图灵模式的形成只需要两个化学物种,但在小型生化系统中,第三个物种对于稳定模式抵御强固有噪声至关重要。
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引用次数: 0
Current rectification via Photosystem I monolayers induced by their orientation on hydrophilic self-assembled monolayers on titanium nitride 氮化钛上亲水自组装单层的取向诱导光系统 I 单层实现电流整流
Pub Date : 2024-08-17 DOI: arxiv-2408.09276
Jonathan Rojas, Zhe Wang, Feng Liu, Jerry A. Fereiro, Domenikos Chryssikos, Thomas Dittrich, Dario Leister, David Cahen, Marc Tornow
Photosystem I (PSI) is a photosynthetic protein which evolved to efficientlytransfer electrons through the thylakoid membrane. This remarkable processattracted the attention of the biomolecular electronics community, which aimsto study and understand the underlying electronic transport through theseproteins by contacting ensembles of PSI with solid-state metallic contacts.This paper extends published work of immobilizing monolayers of PSI with aspecific orientation, by using organophosphonate self-assembled molecules withhydrophilic heads on ultra-flat titanium nitride. Electrical measurementscarried out with eutectic GaIn top contacts showed current rectification ratiosof up to ~200. The previously proposed rectification mechanism, relying on theprotein's internal electric dipole, was inquired by measuring shifts in thework function. Our straightforward bottom-up fabrication method may allow forfurther experimental studies on PSI molecules, such as embedding them insolid-state, transparent top contact schemes for optoelectronic measurements.
光系统 I(PSI)是一种光合作用蛋白质,其进化过程是通过类囊体膜高效传输电子。这一非凡的过程吸引了生物分子电子学界的关注,他们的目标是通过将 PSI 组合与固态金属触头接触,研究和了解通过这些蛋白质进行电子传输的基本原理。本文利用有机膦酸盐自组装分子在超平氮化钛上的亲水头,扩展了已发表的固定 PSI 单层特定取向的工作。使用共晶铟镓顶触点进行的电学测量显示,电流整流比高达 ~200。之前提出的整流机制依赖于蛋白质的内部电偶极子,我们通过测量工作函数的偏移对这一机制进行了探究。我们这种自下而上的直接制备方法可用于对 PSI 分子进行进一步的实验研究,例如将它们嵌入固态透明顶面接触方案中进行光电测量。
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引用次数: 0
Tunable Hyperuniformity in Cellular Structures 细胞结构中的可调超均匀性
Pub Date : 2024-08-16 DOI: arxiv-2408.08976
Yiwen Tang, Xinzhi Li, Dapeng Bi
Hyperuniform materials, characterized by their suppressed densityfluctuations and vanishing structure factors as the wave number approacheszero, represent a unique state of matter that straddles the boundary betweenorder and randomness. These materials exhibit exceptional optical, mechanical,and acoustic properties, making them of great interest in materials science andengineering. Traditional methods for creating hyperuniform structures,including collective-coordinate optimization and centroidal Voronoitessellations, have primarily been computational and face challenges incapturing the complexity of naturally occurring systems. This study introducesa comprehensive theoretical framework to generate hyperuniform structuresinspired by the collective organization of biological cells within anepithelial tissue layer. By adjusting parameters such as cell elasticity andinterfacial tension, we explore a spectrum of hyperuniform states from fluid torigid, each exhibiting distinct mechanical properties and types of densityfluctuations. Our results not only advance the understanding of hyperuniformityin biological tissues but also demonstrate the potential of these materials toinform the design of novel materials with tailored properties.
超均匀材料的特点是当波数趋近于零时,密度波动被抑制,结构因子消失,代表了一种独特的物质状态,跨越了有序性和随机性之间的界限。这些材料具有优异的光学、机械和声学特性,因此在材料科学和工程学领域引起了极大的兴趣。创建超均匀结构的传统方法,包括集合坐标优化和向心Voronoitessellations,主要是计算方法,在捕捉自然发生系统的复杂性方面面临挑战。本研究引入了一个综合理论框架,受上皮组织层中生物细胞集体组织的启发,生成超均匀结构。通过调整细胞弹性和界面张力等参数,我们探索了从流态到僵态的超均匀状态,每种状态都表现出不同的机械特性和密度波动类型。我们的研究结果不仅加深了人们对生物组织超均匀性的理解,还证明了这些材料在为设计具有定制特性的新型材料提供信息方面的潜力。
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引用次数: 0
Active Liquid-Liquid Phase-Separation in a Confining Environment 密闭环境中的活性液-液相分离
Pub Date : 2024-08-15 DOI: arxiv-2408.07876
Chen Lin, Robijn Bruinsma
Active liquid-liquid phase separation (LLPS) in a confining environment isbelieved to play an important role in cell biology. Recently, it was shown thatwhen active noise at the microscopic level is included in the classical theoryof nucleation and growth then this does not cause the breakdown of detailedbalance at the textit{macroscopic} level provided that the droplet radius isthe only collective coordinate. Here, we present a simple model for active LLPSin a confining environment, with the droplet location in a confining potentialas a second collective coordinate, and find that detailed balance textit{is}broken at the macroscopic level in an unusual fashion, using theFluctuation-Dissipation Theorem as a diagnostic.
封闭环境中的活性液-液相分离(LLPS)被认为在细胞生物学中发挥着重要作用。最近的研究表明,当成核与生长的经典理论中包含微观层面的主动噪声时,只要液滴半径是唯一的集合坐标,就不会导致文本{微观}层面的详细平衡崩溃。在这里,我们提出了一个在约束环境中活动的LLPS的简单模型,将液滴在约束势中的位置作为第二个集体坐标,并利用波动-消散定理(Fluctuation-Dissipation Theorem)作为诊断方法,发现详细平衡在宏观水平上以一种不同寻常的方式被打破了。
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引用次数: 0
Enabling microrobotic chemotaxis via reset-free hierarchical reinforcement learning 通过无重置分层强化学习实现微机器人趋化
Pub Date : 2024-08-14 DOI: arxiv-2408.07346
Tongzhao Xiong, Zhaorong Liu, Chong Jin Ong, Lailai Zhu
Microorganisms have evolved diverse strategies to propel in viscous fluids,navigate complex environments, and exhibit taxis in response to stimuli. Thishas inspired the development of synthetic microrobots, where machine learning(ML) is playing an increasingly important role. Can ML endow these robots withintelligence resembling that developed by their natural counterparts overevolutionary timelines? Here, we demonstrate chemotactic navigation of amulti-link articulated microrobot using two-level hierarchical reinforcementlearning (RL). The lower-level RL allows the robot -- featuring either a chainor ring topology -- to acquire topology-specific swimming gaits: wavepropagation characteristic of flagella or body oscillation akin to an ameboid.Such flagellar and ameboid microswimmers, further enabled by the higher-levelRL, accomplish chemotactic navigation in prototypical biologically-relevantscenarios that feature conflicting chemoattractants, pursuing a swimmingbacterial mimic, steering in vortical flows, and squeezing through tightconstrictions. Additionally, we achieve reset-free, partially observable RL,where the robot observes only its joint angles and local scalar quantities.This advancement illuminates solutions for overcoming the persistent challengesof manual resets and partial observability in real-world microrobotic RL.
微生物已经进化出了多种策略,可以在粘性流体中推进、在复杂环境中航行,并在受到刺激时表现出滑行。这启发了合成微型机器人的发展,而机器学习(ML)在其中扮演着越来越重要的角色。机器学习能否赋予这些机器人与自然界中的机器人一样的智能?在这里,我们利用两级分层强化学习(RL)演示了多链节铰接式微型机器人的趋化导航。较低级别的强化学习允许机器人(具有链状或环状拓扑结构)获得拓扑结构特有的游泳步态:鞭毛特有的波状传播或类似于meboid的身体摆动。这种鞭毛和meboid微型游泳机器人在较高级别的强化学习的进一步支持下,在原型生物相关情景中完成趋化导航,这些情景包括冲突的趋化吸引物、追逐游泳的细菌模仿体、在涡流中转向以及挤过狭小的限制。此外,我们还实现了无重置、部分可观测的 RL,在这种情况下,机器人只需观测其关节角度和局部标量。这一进展为克服现实世界中微型机器人 RL 所面临的手动重置和部分可观测性的长期挑战提供了解决方案。
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引用次数: 0
Self-folding Self-replication 自我折叠 自我复制
Pub Date : 2024-08-13 DOI: arxiv-2408.07154
Ralph P. Lano
Inspired by protein folding, we explored the construction ofthree-dimensional structures and machines from one-dimensional chains of simplebuilding blocks. This approach not only allows us to recreate theself-replication mechanism introduced earlier, but also significantlysimplifies the process. We introduced a new set of folding blocks thatfacilitate the formation of secondary structures such as {alpha}-helices andb{eta}-sheets, as well as more advanced tertiary and quaternary structures,including self-replicating machines. The introduction of rotational degrees offreedom leads to a reduced variety of blocks and, most importantly, reduces theoverall size of the machines by a factor of five. In addition, we present auniversal copier-constructor, a highly efficient self-replicating mechanismcomposed of approximately 40 blocks, including the restictions posed on it. Thepaper also addresses evolutionary considerations, outlining several steps onthe evolutionary ladder towards more sophisticated self-replicating systems.Finally, this study offers a clear rationale for nature's preference forone-dimensional chains in constructing three-dimensional structures.
受蛋白质折叠的启发,我们探索了从简单积木的一维链构建三维结构和机器的方法。这种方法不仅能让我们重现之前介绍的自我复制机制,还能大大简化这一过程。我们引入了一组新的折叠块,它们有助于形成二级结构,如{alpha}-螺旋和b{ea}-片,以及更高级的三级和四级结构,包括自我复制机器。旋转自由度的引入减少了块的种类,最重要的是,将机器的整体尺寸缩小了五倍。此外,我们还提出了一种通用的复制器构造器,这是一种高效的自我复制机制,由大约 40 个块组成,包括对它的限制。最后,这项研究为自然界在构建三维结构时偏好使用一维链提供了明确的理论依据。
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引用次数: 0
Kinetoplast DNA: a polymer physicist's Olympic dream Kinetoplast DNA:高分子物理学家的奥运梦想
Pub Date : 2024-08-12 DOI: arxiv-2408.05978
Davide Michieletto
All life forms are miraculous, but some are more inexplicable than others.Trypanosomes are by far one of the most puzzling organisms on Earth: theirmitochondrial genome, also called kinetoplast DNA (kDNA) forms anOlympic-ring-like network of interlinked DNA circles, challenging conventionalparadigms in both biology and physics. In this review, I will discuss kDNA fromthe astonished perspective of a polymer physicist and tell a story of how asingle sub-celluar structure from a blood-dwelling parasite is inspiringgenerations of polymer chemists and physicists to create new catenatedmaterials.
锥虫是迄今为止地球上最令人费解的生物之一:它们的半软核基因组(又称动粒 DNA(kDNA))形成了一个由相互连接的 DNA 圈组成的奥林匹克环状网络,挑战了生物学和物理学的传统范式。在这篇综述中,我将从一个高分子物理学家的惊奇视角来讨论 kDNA,并讲述一个故事:一个来自血栖寄生虫的亚细胞结构是如何激励一代又一代的高分子化学家和物理学家去创造新的复合材料的。
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引用次数: 0
期刊
arXiv - PHYS - Biological Physics
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