Pub Date : 2024-09-10Epub Date: 2024-09-03DOI: 10.1073/pnas.2406471121
Christina L Davis, Jialu Li, Sayumi Miyano
States have long used economic sanctions in response to violations of international law as a strategy to restore order. Increasingly, firms also reject doing business with violators. In response to the war in Ukraine, hundreds of multinational corporations voluntarily withdrew from Russia, even when policymakers were still debating the extent of sanctions. How did firm managers evaluate whether to withdraw from the Russian market? Using a survey experiment with Japanese firm managers conducted three months after the Russian invasion of Ukraine in 2022, we explore how peer effects-information on what other firms are doing in response to the crisis-influence support for withdrawal of business activity with Russia. Our findings show that information about withdrawal by other firms from a diverse set of countries promotes peer conformity that increases support. In contrast, information about ongoing business with Russia by Chinese firms fosters competition that reduces support. Market exposure moderates these reactions, although the concern about peer behavior does not appear to be driven by a reputation mechanism. Our research provides insight into how business actors perceive the strategic interplay of peer influence and market dynamics in the context of geopolitical conflicts.
{"title":"Peer conformity and competition shape how business managers evaluate withdrawals from Russia amid the Ukraine War.","authors":"Christina L Davis, Jialu Li, Sayumi Miyano","doi":"10.1073/pnas.2406471121","DOIUrl":"https://doi.org/10.1073/pnas.2406471121","url":null,"abstract":"<p><p>States have long used economic sanctions in response to violations of international law as a strategy to restore order. Increasingly, firms also reject doing business with violators. In response to the war in Ukraine, hundreds of multinational corporations voluntarily withdrew from Russia, even when policymakers were still debating the extent of sanctions. How did firm managers evaluate whether to withdraw from the Russian market? Using a survey experiment with Japanese firm managers conducted three months after the Russian invasion of Ukraine in 2022, we explore how peer effects-information on what other firms are doing in response to the crisis-influence support for withdrawal of business activity with Russia. Our findings show that information about withdrawal by other firms from a diverse set of countries promotes peer conformity that increases support. In contrast, information about ongoing business with Russia by Chinese firms fosters competition that reduces support. Market exposure moderates these reactions, although the concern about peer behavior does not appear to be driven by a reputation mechanism. Our research provides insight into how business actors perceive the strategic interplay of peer influence and market dynamics in the context of geopolitical conflicts.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Dos Santos,Philip A Downing,Ashleigh S Griffin,Charlie K Cornwallis,Stuart A West
Hamilton's rule provides the cornerstone for our understanding of the evolution of all forms of social behavior, from altruism to spite, across all organisms, from viruses to humans. In contrast to the standard prediction from Hamilton's rule, recent studies have suggested that altruistic helping can be favored even if it does not benefit relatives, as long as it decreases the environmentally induced variance of their reproductive success ("altruistic bet-hedging"). However, previous predictions both rely on an approximation and focus on variance-reducing helping behaviors. We derived a version of Hamilton's rule that fully captures environmental variability. This shows that decreasing (or increasing) the variance in the absolute reproductive success of relatives does not have a consistent effect-it can either favor or disfavor the evolution of helping. We then empirically quantified the effect of helping on the variance in reproductive success across 15 species of cooperatively breeding birds. We found that a) helping did not consistently decrease the variance of reproductive success and often increased it, and b) the mean benefits of helping across environments consistently outweighed other variability components of reproductive success. Altogether, our theoretical and empirical results suggest that the effects of helping on the variability components of reproductive success have not played a consistent or strong role in favoring helping.
{"title":"Altruism and natural selection in a variable environment.","authors":"Miguel Dos Santos,Philip A Downing,Ashleigh S Griffin,Charlie K Cornwallis,Stuart A West","doi":"10.1073/pnas.2402974121","DOIUrl":"https://doi.org/10.1073/pnas.2402974121","url":null,"abstract":"Hamilton's rule provides the cornerstone for our understanding of the evolution of all forms of social behavior, from altruism to spite, across all organisms, from viruses to humans. In contrast to the standard prediction from Hamilton's rule, recent studies have suggested that altruistic helping can be favored even if it does not benefit relatives, as long as it decreases the environmentally induced variance of their reproductive success (\"altruistic bet-hedging\"). However, previous predictions both rely on an approximation and focus on variance-reducing helping behaviors. We derived a version of Hamilton's rule that fully captures environmental variability. This shows that decreasing (or increasing) the variance in the absolute reproductive success of relatives does not have a consistent effect-it can either favor or disfavor the evolution of helping. We then empirically quantified the effect of helping on the variance in reproductive success across 15 species of cooperatively breeding birds. We found that a) helping did not consistently decrease the variance of reproductive success and often increased it, and b) the mean benefits of helping across environments consistently outweighed other variability components of reproductive success. Altogether, our theoretical and empirical results suggest that the effects of helping on the variability components of reproductive success have not played a consistent or strong role in favoring helping.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In interval reproduction tasks, animals must remember the event starting the interval and anticipate the time of the planned response to terminate the interval. The interval reproduction task thus allows for studying both memory for the past and anticipation of the future. We analyzed previously published recordings from the rodent medial prefrontal cortex [J. Henke et al., eLife10, e71612 (2021)] during an interval reproduction task and identified two cell groups by modeling their temporal receptive fields using hierarchical Bayesian models. The firing in the "past cells" group peaked at the start of the interval and relaxed exponentially back to baseline. The firing in the "future cells" group increased exponentially and peaked right before the planned action at the end of the interval. Contrary to the previous assumption that timing information in the brain has one or two time scales for a given interval, we found strong evidence for a continuous distribution of the exponential rate constants for both past and future cell populations. The real Laplace transformation of time predicts exponential firing with a continuous distribution of rate constants across the population. Therefore, the firing pattern of the past cells can be identified with the Laplace transform of time since the past event while the firing pattern of the future cells can be identified with the Laplace transform of time until the planned future event.
在间隔再现任务中,动物必须记住开始间隔的事件,并预测计划反应的时间以终止间隔。因此,间隔再现任务既可以研究对过去的记忆,也可以研究对未来的预测。我们分析了之前发表的啮齿动物内侧前额叶皮层在时间间隔再现任务中的记录[J. Henke et al., eLife10, e71612 (2021)],并通过使用分层贝叶斯模型对其时间感受野进行建模,确定了两个细胞群。过去细胞 "组的点燃在间歇开始时达到峰值,然后以指数形式放松回到基线。而 "未来细胞 "组的点燃呈指数增长,并在间隔结束时计划行动之前达到峰值。与以往认为大脑中的定时信息在给定时间间隔内有一个或两个时间尺度的假设相反,我们发现了强有力的证据,证明过去和未来细胞群的指数速率常数呈连续分布。时间的实际拉普拉斯变换预示着整个群体的指数发射率常数呈连续分布。因此,过去细胞的点火模式可以用过去事件发生后时间的拉普拉斯变换来确定,而未来细胞的点火模式可以用计划未来事件发生前时间的拉普拉斯变换来确定。
{"title":"Ramping cells in the rodent medial prefrontal cortex encode time to past and future events via real Laplace transform.","authors":"Rui Cao,Ian M Bright,Marc W Howard","doi":"10.1073/pnas.2404169121","DOIUrl":"https://doi.org/10.1073/pnas.2404169121","url":null,"abstract":"In interval reproduction tasks, animals must remember the event starting the interval and anticipate the time of the planned response to terminate the interval. The interval reproduction task thus allows for studying both memory for the past and anticipation of the future. We analyzed previously published recordings from the rodent medial prefrontal cortex [J. Henke et al., eLife10, e71612 (2021)] during an interval reproduction task and identified two cell groups by modeling their temporal receptive fields using hierarchical Bayesian models. The firing in the \"past cells\" group peaked at the start of the interval and relaxed exponentially back to baseline. The firing in the \"future cells\" group increased exponentially and peaked right before the planned action at the end of the interval. Contrary to the previous assumption that timing information in the brain has one or two time scales for a given interval, we found strong evidence for a continuous distribution of the exponential rate constants for both past and future cell populations. The real Laplace transformation of time predicts exponential firing with a continuous distribution of rate constants across the population. Therefore, the firing pattern of the past cells can be identified with the Laplace transform of time since the past event while the firing pattern of the future cells can be identified with the Laplace transform of time until the planned future event.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-06DOI: 10.1073/pnas.2407455121
Ji Yeon Kim, Jong An Lee, Jung Ho Ahn, Sang Yup Lee
Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Although the importance of magnesium (Mg2+) ion on SA production has been evident from our previous studies, the role of Mg2+ ion remains largely unexplored. In this study, we investigated the impact of Mg2+ ion on SA production and developed a hyper-SA producing strain of M. succiniciproducens by reconstructing the Mg2+ ion transport system. To achieve this, optimal alkaline neutralizer comprising Mg2+ ion was developed and the physiological effect of Mg2+ ion was analyzed. Subsequently, the Mg2+ ion transport system was reconstructed by introducing an efficient Mg2+ ion transporter from Salmonella enterica. A high-inoculum fed-batch fermentation of the final engineered strain produced 152.23 ± 0.99 g/L of SA, with a maximum productivity of 39.64 ± 0.69 g/L/h. These findings highlight the importance of Mg2+ ions and transportation system optimization in succinic acid production by M. succiniciproducens.
{"title":"High-level succinic acid production by overexpressing a magnesium transporter in <i>Mannheimia succiniciproducens</i>.","authors":"Ji Yeon Kim, Jong An Lee, Jung Ho Ahn, Sang Yup Lee","doi":"10.1073/pnas.2407455121","DOIUrl":"https://doi.org/10.1073/pnas.2407455121","url":null,"abstract":"<p><p>Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered <i>Mannheimia succiniciproducens</i>. Although the importance of magnesium (Mg<sup>2+</sup>) ion on SA production has been evident from our previous studies, the role of Mg<sup>2+</sup> ion remains largely unexplored. In this study, we investigated the impact of Mg<sup>2+</sup> ion on SA production and developed a hyper-SA producing strain of <i>M. succiniciproducens</i> by reconstructing the Mg<sup>2+</sup> ion transport system. To achieve this, optimal alkaline neutralizer comprising Mg<sup>2+</sup> ion was developed and the physiological effect of Mg<sup>2+</sup> ion was analyzed. Subsequently, the Mg<sup>2+</sup> ion transport system was reconstructed by introducing an efficient Mg<sup>2+</sup> ion transporter from <i>Salmonella enterica</i>. A high-inoculum fed-batch fermentation of the final engineered strain produced 152.23 ± 0.99 g/L of SA, with a maximum productivity of 39.64 ± 0.69 g/L/h. These findings highlight the importance of Mg<sup>2+</sup> ions and transportation system optimization in succinic acid production by <i>M. succiniciproducens</i>.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-03DOI: 10.1073/pnas.2408067121
Cristina de la Malla, Martina Poletti
Humans explore visual scenes by alternating short fixations with saccades directing the fovea to points of interest. During fixation, the visual system not only examines the foveal stimulus at high resolution, but it also processes the extrafoveal input to plan the next saccade. Although foveal analysis and peripheral selection occur in parallel, little is known about the temporal dynamics of foveal and peripheral processing upon saccade landing, during fixation. Here we investigate whether the ability to localize changes across the visual field differs depending on when the change occurs during fixation, and on whether the change localization involves foveal, extrafoveal processing, or both. Our findings reveal that the ability to localize changes in peripheral areas of the visual field improves as a function of time after fixation onset, whereas localization accuracy for foveal stimuli remains approximately constant. Importantly, this pattern holds regardless of whether individuals monitor only foveal or peripheral stimuli, or both simultaneously. Altogether, these results show that the visual system is more attuned to the foveal input early on during fixation, whereas change localization for peripheral stimuli progressively improves throughout fixation, possibly as a consequence of an increased readiness to plan the next saccade.
{"title":"Different temporal dynamics of foveal and peripheral visual processing during fixation.","authors":"Cristina de la Malla, Martina Poletti","doi":"10.1073/pnas.2408067121","DOIUrl":"10.1073/pnas.2408067121","url":null,"abstract":"<p><p>Humans explore visual scenes by alternating short fixations with saccades directing the fovea to points of interest. During fixation, the visual system not only examines the foveal stimulus at high resolution, but it also processes the extrafoveal input to plan the next saccade. Although foveal analysis and peripheral selection occur in parallel, little is known about the temporal dynamics of foveal and peripheral processing upon saccade landing, during fixation. Here we investigate whether the ability to localize changes across the visual field differs depending on when the change occurs during fixation, and on whether the change localization involves foveal, extrafoveal processing, or both. Our findings reveal that the ability to localize changes in peripheral areas of the visual field improves as a function of time after fixation onset, whereas localization accuracy for foveal stimuli remains approximately constant. Importantly, this pattern holds regardless of whether individuals monitor only foveal or peripheral stimuli, or both simultaneously. Altogether, these results show that the visual system is more attuned to the foveal input early on during fixation, whereas change localization for peripheral stimuli progressively improves throughout fixation, possibly as a consequence of an increased readiness to plan the next saccade.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-06DOI: 10.1073/pnas.2404748121
Marco Fritzsche, Karsten Kruse
Mechanical force has repeatedly been highlighted to be involved in T cell activation. However, the biological significance of mechanical force for T cell receptor signaling remains under active consideration. Here, guided by theoretical analysis, we provide a perspective on how mechanical forces between a T cell and an antigen-presenting cell can influence the bond of a single T cell receptor major histocompatibility complex during early T cell activation. We point out that the lifetime of T cell receptor bonds and thus the degree of their phosphorylation which is essential for T cell activation depends considerably on the T cell receptor rigidity and the average magnitude and frequency of an applied oscillatory force. Such forces could be, for example, produced by protrusions like microvilli during early T cell activation or invadosomes during full T cell activation. These features are suggestive of mechanical force being exploited by T cells to advance self-nonself discrimination in early T cell activation.
人们一再强调,机械力与 T 细胞活化有关。然而,机械力对 T 细胞受体信号转导的生物学意义仍在积极探索之中。在此,我们以理论分析为指导,从一个角度探讨了在早期 T 细胞活化过程中,T 细胞与抗原递呈细胞之间的机械力如何影响单个 T 细胞受体主要组织相容性复合物的结合。我们指出,T 细胞受体结合的寿命,以及对 T 细胞活化至关重要的磷酸化程度,在很大程度上取决于 T 细胞受体的刚性以及外加振荡力的平均大小和频率。例如,在 T 细胞早期活化过程中,微绒毛等突起物会产生这种力;在 T 细胞完全活化过程中,内含体也会产生这种力。这些特征表明,在早期 T 细胞活化过程中,T 细胞利用机械力来促进自我与非自我的分辨。
{"title":"Mechanical force matters in early T cell activation.","authors":"Marco Fritzsche, Karsten Kruse","doi":"10.1073/pnas.2404748121","DOIUrl":"https://doi.org/10.1073/pnas.2404748121","url":null,"abstract":"<p><p>Mechanical force has repeatedly been highlighted to be involved in T cell activation. However, the biological significance of mechanical force for T cell receptor signaling remains under active consideration. Here, guided by theoretical analysis, we provide a perspective on how mechanical forces between a T cell and an antigen-presenting cell can influence the bond of a single T cell receptor major histocompatibility complex during early T cell activation. We point out that the lifetime of T cell receptor bonds and thus the degree of their phosphorylation which is essential for T cell activation depends considerably on the T cell receptor rigidity and the average magnitude and frequency of an applied oscillatory force. Such forces could be, for example, produced by protrusions like microvilli during early T cell activation or invadosomes during full T cell activation. These features are suggestive of mechanical force being exploited by T cells to advance self-nonself discrimination in early T cell activation.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-05DOI: 10.1073/pnas.2321021121
Stephanie K Bonney, Cara D Nielson, Maria J Sosa, Orla Bonnar, Andy Y Shih
In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion.
{"title":"Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.","authors":"Stephanie K Bonney, Cara D Nielson, Maria J Sosa, Orla Bonnar, Andy Y Shih","doi":"10.1073/pnas.2321021121","DOIUrl":"https://doi.org/10.1073/pnas.2321021121","url":null,"abstract":"<p><p>In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-08-30DOI: 10.1073/pnas.2412390121
László G Boros, Stephanie Seneff, Marianna Túri, László Palcsu, Roman A Zubarev
{"title":"Active involvement of compartmental, inter- and intramolecular deuterium disequilibrium in adaptive biology.","authors":"László G Boros, Stephanie Seneff, Marianna Túri, László Palcsu, Roman A Zubarev","doi":"10.1073/pnas.2412390121","DOIUrl":"10.1073/pnas.2412390121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-04DOI: 10.1073/pnas.2405382121
Ian A Coates, William Pan, Max A Saccone, Gabriel Lipkowitz, Dan Ilyin, Madison M Driskill, Maria T Dulay, Curtis W Frank, Eric S G Shaqfeh, Joseph M DeSimone
Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution. We demonstrate the ability to resolve 50-μm microchannels, breaking the historical relationship between resin properties and negative space resolution. With this approach, we fabricated proof-of-concept 3D free-form microfluidic devices with improved design freedom over device material selection and resulting properties.
立体光刻技术能够通过光诱导聚合制造三维(3D)自由形态结构。然而,滞留在负空间(如微流道或空隙)中的树脂内的紫外线剂量累积会导致这些负空间意外关闭,即所谓的过固化。我们报告了利用注射连续液体界面生产技术,用新鲜树脂连续置换前层负空间中可能过固化的树脂,以减轻 Z 轴分辨率的损失。我们展示了分辨 50 微米微通道的能力,打破了树脂特性与负空间分辨率之间的历史关系。利用这种方法,我们制造出了概念验证型三维自由形态微流控器件,提高了器件材料选择和所产生特性的设计自由度。
{"title":"High-resolution stereolithography: Negative spaces enabled by control of fluid mechanics.","authors":"Ian A Coates, William Pan, Max A Saccone, Gabriel Lipkowitz, Dan Ilyin, Madison M Driskill, Maria T Dulay, Curtis W Frank, Eric S G Shaqfeh, Joseph M DeSimone","doi":"10.1073/pnas.2405382121","DOIUrl":"https://doi.org/10.1073/pnas.2405382121","url":null,"abstract":"<p><p>Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution. We demonstrate the ability to resolve 50-μm microchannels, breaking the historical relationship between resin properties and negative space resolution. With this approach, we fabricated proof-of-concept 3D free-form microfluidic devices with improved design freedom over device material selection and resulting properties.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10Epub Date: 2024-09-03DOI: 10.1073/pnas.2322155121
Derek J Urwin, Elise Tran, Anastassia N Alexandrova
Utilizing molecular dynamics and free energy perturbation, we examine the relative binding affinity of several covalent polycyclic aromatic hydrocarbon - DNA (PAH-DNA) adducts at the central adenine of NRAS codon-61, a mutational hotspot implicated in cancer risk. Several PAHs classified by the International Agency for Research on Cancer as probable, possible, or unclassifiable as to carcinogenicity are found to have greater binding affinity than the known carcinogen, benzo[a]pyrene (B[a]P). van der Waals interactions between the intercalated PAH and neighboring nucleobases, and minimal disruption of the DNA duplex drive increases in binding affinity. PAH-DNA adducts may be repaired by global genomic nucleotide excision repair (GG-NER), hence we also compute relative free energies of complexation of PAH-DNA adducts with RAD4-RAD23 (the yeast ortholog of human XPC-RAD23) which constitutes the recognition step in GG-NER. PAH-DNA adducts exhibiting the greatest DNA binding affinity also exhibit the least RAD4-RAD23 complexation affinity and are thus predicted to resist the GG-NER machinery, contributing to their genotoxic potential. In particular, the fjord region PAHs dibenzo[a,l]pyrene, benzo[g]chrysene, and benzo[c]phenanthrene are found to have greater binding affinity while having weaker RAD4-RAD23 complexation affinity than their respective bay region analogs B[a]P, chrysene, and phenanthrene. We also find that the bay region PAHs dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, and dibenzo[a,h]anthracene exhibit greater binding affinity and weaker RAD4-RAD23 complexation affinity than B[a]P. Thus, the study of PAH genotoxicity likely needs to be substantially broadened, with implications for public policy and the health sciences. This approach can be broadly applied to assess factors contributing to the genotoxicity of other unclassified compounds.
{"title":"Relative genotoxicity of polycyclic aromatic hydrocarbons inferred from free energy perturbation approaches.","authors":"Derek J Urwin, Elise Tran, Anastassia N Alexandrova","doi":"10.1073/pnas.2322155121","DOIUrl":"https://doi.org/10.1073/pnas.2322155121","url":null,"abstract":"<p><p>Utilizing molecular dynamics and free energy perturbation, we examine the relative binding affinity of several covalent polycyclic aromatic hydrocarbon - DNA (PAH-DNA) adducts at the central adenine of NRAS codon-61, a mutational hotspot implicated in cancer risk. Several PAHs classified by the International Agency for Research on Cancer as probable, possible, or unclassifiable as to carcinogenicity are found to have greater binding affinity than the known carcinogen, benzo[a]pyrene (B[a]P). van der Waals interactions between the intercalated PAH and neighboring nucleobases, and minimal disruption of the DNA duplex drive increases in binding affinity. PAH-DNA adducts may be repaired by global genomic nucleotide excision repair (GG-NER), hence we also compute relative free energies of complexation of PAH-DNA adducts with RAD4-RAD23 (the yeast ortholog of human XPC-RAD23) which constitutes the recognition step in GG-NER. PAH-DNA adducts exhibiting the greatest DNA binding affinity also exhibit the least RAD4-RAD23 complexation affinity and are thus predicted to resist the GG-NER machinery, contributing to their genotoxic potential. In particular, the fjord region PAHs dibenzo[a,l]pyrene, benzo[g]chrysene, and benzo[c]phenanthrene are found to have greater binding affinity while having weaker RAD4-RAD23 complexation affinity than their respective bay region analogs B[a]P, chrysene, and phenanthrene. We also find that the bay region PAHs dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, and dibenzo[a,h]anthracene exhibit greater binding affinity and weaker RAD4-RAD23 complexation affinity than B[a]P. Thus, the study of PAH genotoxicity likely needs to be substantially broadened, with implications for public policy and the health sciences. This approach can be broadly applied to assess factors contributing to the genotoxicity of other unclassified compounds.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}