Dynamics of cross-platform attention to retracted papers

Retracted papers often circulate widely on social media, digital news, and other websites before their official retraction. The spread of potentially inaccurate or misleading results from retracted papers can harm the scientific community and the public. Here, we quantify the amount and type of attention 3,851 retracted papers received over time in different online platforms. Comparing with a set of nonretracted control papers from the same journals with similar publication year, number of coauthors, and author impact, we show that retracted papers receive more attention after publication not only on social media but also, on heavily curated platforms, such as news outlets and knowledge repositories, amplifying the negative impact on the public. At the same time, we find that posts on Twitter tend to express more criticism about retracted than about control papers, suggesting that criticism-expressing tweets could contain factual information about problematic papers. Most importantly, around the time they are retracted, papers generate discussions that are primarily about the retraction incident rather than about research findings, showing that by this point, papers have exhausted attention to their results and highlighting the limited effect of retractions. Our findings reveal the extent to which retracted papers are discussed on different online platforms and identify at scale audience criticism toward them. In this context, we show that retraction is not an effective tool to reduce online attention to problematic papers.

Retraction in academic publishing is an important and necessary mechanism for science to self-correct (1). Prior studies have shown that the number of retractions has increased in recent years (2–5). This rise can be explained by many different factors (3–7). One reason is that the number of publications is increasing exponentially (8). Meanwhile, as scientific research has become more complex and interdisciplinary than ever before, reviewers are facing a higher cognitive burden (9, 10). This undermines the scientific community’s ability to filter out problematic papers. In fact, research shows that prominent journals with rigorous screening and high publishing standards are as likely to publish erroneous papers as less prominent journals (11). Finally, not all retractions are due to research fraud—some papers are retracted due to unintentional errors or mistakes, which become more likely as research data grow in size and complexity (6).Regardless of the reasons behind this increase, a high incidence of retractions in academic literature has the potential to undermine the credibility of scientific communities and reduce public trust in science (6, 12). What is more, the circulation of misleading findings can be harmful to the lay public (6, 13–15), especially given how broadly papers can be disseminated via social media (16). For instance, there are 2 retracted papers among the 10 most highly shared papers in 2020 according to Altmetric, a service that tracks the online dissemination of scientific articles (17). One of them, published in a top biology journal, reported that treatment with chloroquine had no benefit in COVID-19 patients based on data that were likely fabricated (18). Another paper, published in a well-regarded general interest journal, falsely claimed that having more female mentors was negatively correlated with postmentorship impact of junior scholars (19). Both papers attracted considerable attention before they were retracted, raising questions about their possible negative impact on online audiences’ trust in science.As these examples suggest, retracted papers can attain substantial online attention, and potentially flawed knowledge can reach the public, which often is impacted by the research results (20). This large-scale spreading of papers occurs as the web has become the primary channel through which the lay public interacts with scientific information (21–23). Past research on the online diffusion of science has mainly studied the spread of papers without regard to their retraction status (24–29). Other work has examined the dissemination of retracted papers in scientific communities, focusing mainly on the associated citation penalty (5, 14, 30–36).However, the impact of retraction on the online dissemination of retracted papers is unclear. Here, we address this essential open question. Past research found that authors tend to keep citing retracted papers long after they have been red flagged, although at a lower rate (5, 6, 12, 14). This raises the question of whether retraction is effective in reducing public attention beyond the academic literature. Studying the impact of retraction relative to the temporal “trajectory” of mentions a paper receives could be helpful for journals to devise policies and practices that maximize the effect of retractions (12, 37).To understand whether retraction is appropriate for reducing dissemination online, we first assess the extent of online circulation of erroneous findings by investigating variations in how often retracted papers are mentioned on different types of platforms before and after retraction. Recent research indicates that, overall, retracted papers tend to receive more attention than nonretracted ones (38). Prior work also showed that retractions occur most frequently among highly cited articles published in high-impact journals (11, 39), suggesting a counterintuitive link between rigorous screening and retraction. Is there a similar tendency online where retracted papers receive more attention on carefully curated platforms, such as news outlets, than on platforms with limited entry barriers, like social media sites? Such a trend would highlight difficulties with identifying unreliable research given their broad visibility in established venues and could inform attempts to manage the harm caused by retractions. Second, we distinguish between critical and uncritical attention to papers to uncover how retracted research is mentioned. More than half of retracted papers are flagged because of scientific misconduct, such as fabrication, falsification, and plagiarism (4, 5). These papers may receive lots of attention due to criticism raised by online audiences. Is the attention received by retracted papers due to sharing without knowing about the mistakes of a paper, or is it rather expressing concerns (so-called “critical” mentions)? As suggested in a recent case study (40), knowing how retracted papers are mentioned may uncover users who are improving science-related discussions on Twitter by identifying papers that require a closer examination.In this paper, we compiled a dataset to quantify the volume of attention that 3,985 retracted papers received on 14 online platforms (e.g., public social media posts on Twitter, Facebook, and Reddit), their coverage in online news, citations in Wikipedia, and research blogs. We compared their attention with nonretracted papers selected through a matching process based on publication venue and year, number of authors, and authors’ citation count (Fig. 1A and Identifying Control Papers). We obtained retracted papers from Retraction Watch (41), the largest database to date that records retracted papers, and pulled their complete trajectory of mentions over time on various platforms from a service called Altmetric (42) that has been tracking posts about research papers for the past decade. The granularity and scale of the data enabled us to differentiate mentions on four different types of platforms, including social media, news media, blogs, and knowledge repositories (Fig. 1 B and C). We thus provide a systematic investigation of the online mentions of papers disentangled by platform during the time periods between publication and retraction (Fig. 1D) and after retraction (Fig. 1E).Open in a separate windowFig. 1.Illustration of the research process that compares the online attention received by retracted and control papers. (A) We match five control papers to each retracted paper using the Altmetric database. (B and C) We track the change in mentions over time on four different types of platforms and in top news outlets. As an example, we show here the retracted paper “Effect of a program combining transitional care and long-term self-management support on outcomes of hospitalized patients with chronic obstructive pulmonary disease: A randomized clinical trial” published in JAMA (DOI: 10.1001/jama.2018.17933) and one of its matched control papers: “Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: US Preventive Services Task Force Recommendation Statement” (DOI: 10.1001/jama.2018.3185). (D) We compute the average cumulative number of mentions across all platforms within 6 mo after publication (and before retraction) for all retracted and control papers in the dataset. (E) Similarly, we compute the average cumulative number of mentions within 6 mo after retraction. Error bars indicate 95% CIs.Our findings offer insights into how extensively retracted papers are mentioned in different online platforms over time and how frequent their critical vs. uncritical discussion is on Twitter. Most importantly, we show that retractions are not reducing harmful dissemination of problematic research on any of the platforms studied here because by the time the retraction is issued, most papers have exhausted their online attention. We also contribute a large dataset of identifiers of tweets that mention the papers used in this study and human annotations of whether the tweets express criticism with respect to the findings of the papers (Labeling Critical Tweets). This dataset (43) can be useful to the broader research community for the study of criticism toward scientific articles and can aid the development of automated methods to detect criticism computationally (44).     

Chlorination of arenes via the degradation of toxic chlorophenols

Aryl chlorides are among the most versatile synthetic precursors, and yet inexpensive and benign chlorination techniques to produce them are underdeveloped. We propose a process to generate aryl chlorides by chloro-group transfer from chlorophenol pollutants to arenes during their mineralization, catalyzed by Cu(NO₃)₂/NaNO₃ under aerobic conditions. A wide range of arene substrates have been chlorinated using this process. Mechanistic studies show that the Cu catalyst acts in cooperation with NO_x species generated from the decomposition of NaNO₃ to regulate the formation of chlorine radicals that mediate the chlorination of arenes together with the mineralization of chlorophenol. The selective formation of aryl chlorides with the concomitant degradation of toxic chlorophenol pollutants represents a new approach in environmental pollutant detoxication. A reduction in the use of traditional chlorination reagents provides another (indirect) benefit of this procedure.

Chlorophenols are widely encountered moieties present in herbicides, drugs, and pesticides (1). Owing to the high dissociation energies of carbon‒chloride bonds, chlorophenols biodegrade very slowly, and their prolonged exposure leads to severe ecological and environmental problems (Fig. 1A) (2–4). Several well-established technologies have been developed for the treating of chlorophenols, including catalytic oxidation (5–11), biodegradation (12–15), solvent extraction (16, 17), and adsorption (18–20) Among these methods, adsorption is the most versatile and widely used method due to its high removal efficiency and simple operation, but the resulting products are of no value, and consequently, these processes are not viable.Open in a separate windowFig. 1.Background and reaction design. (A) Examples of chlorophenol pollutants. (B) Examples of aryl chlorides. (C) The chlorination process reported herein was based on chloro-group transfer from chlorophenol pollutants.With the extensive application of substitution reactions (21, 22), transfunctionalizations (23, 24), and cross-coupling reactions (25, 26), aryl chlorides are regarded as one of the most important building blocks widely used in the manufacture of polymers, pharmaceuticals, and other types of chemicals and materials (Fig. 1B) (27–31). Chlorination of arenes is usually carried out with toxic and corrosive reagents (32–34). Less toxic and more selective chlorination reagents tend to be expensive [e.g., chloroamides (35, 36)] and are not atom economic (37–39). Consequently, from the perspective of sustainability, the ability to transfer a chloro group from unwanted chlorophenols to other substrates would be advantageous.Catalytic isofunctional reactions, including transfer hydrogenation and alkene metathesis, have been widely exploited in organic synthesis. We hypothesized that chlorination of arenes also could be achieved by chloro-group transfer, and since stockpiles of chlorophenols tend to be destroyed by mineralization and chlorophenol pollutants may be concentrated by adsorption (18–20), they could be valorized as chlorination reagents via transfer of the chloro group to arene substrates during their mineralization, thereby adding value to the destruction process (Fig. 1C). Although chlorophenol pollutants are not benign, their application as chlorination reagents, with their concomitant destruction to harmless compounds, may be considered as not only meeting the criteria of green chemistry but also potentially surpassing it. Herein, we describe a robust strategy to realize chloro-group transfer from chlorophenol pollutants to arenes and afford a wide range of value-added aryl chlorides.     

Effect of distracting faces on visual selective attention in the monkey

In primates, visual stimuli with social and emotional content tend to attract attention. Attention might be captured through rapid, automatic, subcortical processing or guided by slower, more voluntary cortical processing. Here we examined whether irrelevant faces with varied emotional expressions interfere with a covert attention task in macaque monkeys. In the task, the monkeys monitored a target grating in the periphery for a subtle color change while ignoring distracters that included faces appearing elsewhere on the screen. The onset time of distracter faces before the target change, as well as their spatial proximity to the target, was varied from trial to trial. The presence of faces, especially faces with emotional expressions interfered with the task, indicating a competition for attentional resources between the task and the face stimuli. However, this interference was significant only when faces were presented for greater than 200 ms. Emotional faces also affected saccade velocity and reduced pupillary reflex. Our results indicate that the attraction of attention by emotional faces in the monkey takes a considerable amount of processing time, possibly involving cortical–subcortical interactions. Intranasal application of the hormone oxytocin ameliorated the interfering effects of faces. Together these results provide evidence for slow modulation of attention by emotional distracters, which likely involves oxytocinergic brain circuits.An important issue in understanding the processing of significant affective stimuli is the extent to which these stimuli compete with ongoing tasks in normal healthy individuals. It is generally agreed that there exists attentional bias toward emotional faces in humans as well as other primates (1, 2). However, it is uncertain whether emotional faces trigger attentional capture, which we define as an immediate shift of visual attention at the expense of other stimuli.Affective reactions can be evoked with minimal cognitive processing (3). For instance, presentation of emotional faces under reduced awareness by masking activates the amygdala (4, 5) and produces pupillary (6) and skin conductance responses (7). An immediate response to affectively salient stimuli is thought possible through a direct subcortical pathway via the amygdala, bypassing the primary sensory cortex (8). This activity could then influence allocation of attentional resources in the cortex (9, 10). Consistent with this, emotional faces capture attention in visual search (11–13), even when irrelevant to the task at hand. Based on these findings, one would predict that emotional faces will interfere with a primary attention task.However, shifts of attention to emotional stimuli are likely not obligatory in every circumstance. Some studies indicate that capture only occurs in low perceptual load conditions (14, 15). Functional MRI (fMRI) has shown that the amygdala response to affective stimuli is modulated by task demands (16, 17). Also, capture is not entirely stimulus driven, but may be dependent on overlap between the current attentional set and the stimulus that does the capturing (18, 19). In a larger sense, goals and expectations influence capture (20). These factors are more cognitive in nature and possibly involve cortical processing. It has been proposed that the subcortical affective response depends on cortical processing (21). When cortical resources are fully taken up by a primary task, affective stimuli may not get any processing advantage and therefore may not interfere with the task.In the present study, three monkeys detected a subtle color change in an attended target while faces of conspecifics were presented as distracters (Fig. 1). Attentional capture of the faces was measured in terms of reduction in sensitivity for detecting the color change. We found that face distracters did influence monkeys’ performance and reaction time (RT), as well as affected their eye velocity and pupillary dilatation, especially when the faces had a threat expression. Importantly, these influences were dependent on presentation duration of the face images, suggesting that shifts of attention toward the faces were not immediate.Open in a separate windowFig. 1.Methods. (A) Illustration of screen events in the task. (B) Timeline of screen events with possible times that image onset and target/distracter change could occur. (C) Examples of facial expressions of one individual in the stimulus set. From left to right: neutral, threat, fear grin, and lip smack. Fear grin and lip smack were combined.Although different viewpoints predict different roles for cortical and subcortical pathways, there seems to be general agreement that preexisting bias affects how attention is allocated. For example, anxiety is often associated with bias toward fear-relevant information (22–26). To manipulate our subjects’ bias toward faces, we administered the hormone oxytocin (OT). It has been shown that inhalation of OT increases attention to eyes (27, 28) and ability to read emotions from facial expressions (29). In monkeys, OT was shown to blunt social vigilance (30). We found that OT reduced interference on our task, indicating a link between oxytocinergic circuits and attentional circuits.     

Self-assembly of amphiphilic Janus dendrimers into uniform onion-like dendrimersomes with predictable size and number of bilayers

A constitutional isomeric library synthesized by a modular approach has been used to discover six amphiphilic Janus dendrimer primary structures, which self-assemble into uniform onion-like vesicles with predictable dimensions and number of internal bilayers. These vesicles, denoted onion-like dendrimersomes, are assembled by simple injection of a solution of Janus dendrimer in a water-miscible solvent into water or buffer. These dendrimersomes provide mimics of double-bilayer and multibilayer biological membranes with dimensions and number of bilayers predicted by the Janus compound concentration in water. The simple injection method of preparation is accessible without any special equipment, generating uniform vesicles, and thus provides a promising tool for fundamental studies as well as technological applications in nanomedicine and other fields.Most living organisms contain single-bilayer membranes composed of lipids, glycolipids, cholesterol, transmembrane proteins, and glycoproteins (1). Gram-negative bacteria (2, 3) and the cell nucleus (4), however, exhibit a strikingly special envelope that consists of a concentric double-bilayer membrane. More complex membranes are also encountered in cells and their various organelles, such as multivesicular structures of eukaryotic cells (5) and endosomes (6), and multibilayer structures of endoplasmic reticulum (7, 8), myelin (9, 10), and multilamellar bodies (11, 12). This diversity of biological membranes inspired corresponding biological mimics. Liposomes (Fig. 1) self-assembled from phospholipids are the first mimics of single-bilayer biological membranes (13–16), but they are polydisperse, unstable, and permeable (14). Stealth liposomes coassembled from phospholipids, cholesterol, and phospholipids conjugated with poly(ethylene glycol) exhibit improved stability, permeability, and mechanical properties (17–20). Polymersomes (21–24) assembled from amphiphilic block copolymers exhibit better mechanical properties and permeability, but are not always biocompatible and are polydisperse. Dendrimersomes (25–28) self-assembled from amphiphilic Janus dendrimers and minidendrimers (26–28) have also been elaborated to mimic single-bilayer biological membranes. Amphiphilic Janus dendrimers take advantage of multivalency both in their hydrophobic and hydrophilic parts (23, 29–32). Dendrimersomes are assembled by simple injection (33) of a solution of an amphiphilic Janus dendrimer (26) in a water-soluble solvent into water or buffer and produce uniform (34), impermeable, and stable vesicles with excellent mechanical properties. In addition, their size and properties can be predicted by their primary structure (27). Amphiphilic Janus glycodendrimers self-assemble into glycodendrimersomes that mimic the glycan ligands of biological membranes (35). They have been demonstrated to be bioactive toward biomedically relevant bacterial, plant, and human lectins, and could have numerous applications in nanomedicine (20).Open in a separate windowFig. 1.Strategies for the preparation of single-bilayer vesicles and multibilayer onion-like vesicles.More complex and functional cell mimics such as multivesicular vesicles (36, 37) and multibilayer onion-like vesicles (38–40) have also been discovered. Multivesicular vesicles compartmentalize a larger vesicle (37) whereas multibilayer onion-like vesicles consist of concentric alternating bilayers (40). Currently multibilayer vesicles are obtained by very complex and time-consuming methods that do not control their size (39) and size distribution (40) in a precise way. Here we report the discovery of “single–single” (28) amphiphilic Janus dendrimer primary structures that self-assemble into uniform multibilayer onion-like dendrimersomes (Fig. 1) with predictable size and number of bilayers by simple injection of their solution into water or buffer.     

Enabling multiple intercavity polariton coherences by adding quantum confinement to cavity molecular polaritons

In this study, the “particle in a box” idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence. The simulation based on Lindblad equation showed that because the quartet of polariton states resided in the same cavity, they were specifically robust toward decoherence caused by fluctuations in space. The multiple robust coherences paved the way for entangled states and coherent interactions between cavity polaritons, which would be critical for advancing polariton-based quantum information technology.

Molecular vibrational polaritons (1–18) are half-matter, half-light quasiparticles that possess unique abilities to change chemical reactions (3, 10, 12, 15, 17, 19–22), modify energy transfer pathways (7, 14, 23, 24), and have the potential to be an alternative platform for quantum simulation (9, 25–32). When the collective dipole coupling between cavity photon modes and molecular vibrational modes is so strong that the two modes exchange energy at a rate faster than the lifetimes of either mode, the upper and lower polaritons (UP and LP) are formed and the systems reach the so-called vibrational strong coupling (VSC) regime (31–33). Up to now, the majority of molecular vibrational polaritons are formed in Fabry-Perot (FP) cavity, which has one corresponding cavity photon mode for each specific in-plane momentum. These modes at different in-plane momentum form a continuous parabolic dispersion curve. As such, an FP cavity can support only one pair of UP and LP at a specific in-plane momentum, and thereby, have one coherence (30) (i.e., off-diagonal density matrix elements), namely |UP〉〈LP| (or its complex conjugate, Fig. 1A). Thus, UP and LP can be treated as one polariton qubit system at ambient conditions (28, 29, 34).Open in a separate windowFig. 1.Challenges of creating multiple coherences in cavity polaritons. (A) In an FP cavity composed by two flat mirrors, one pair of UP and LP is supported and thereby can only form one coherence |UP〉〈LP| and its conjugate. (B) In the dual cavity, two cavity modes are supported due to the longitudinal cavity thickness difference along the lateral dimension. This cavity can support two pairs of UP and LP and enrich the varieties of coherences. However, coherences such as |UP_B〉〈LP_A| cannot survive the fluctuations between cavities. (C) In this work, we demonstrated the confined cavity by implementing the “particle in a box” concept. In this way, two cavity modes and two pairs of polariton modes are supported in the same spatial location, enabling the creation of coherences among any pairs of polaritons. To clearly show the confinement in the illustration, the vertical dimension was exaggerated. (D) A close view of the confined-cavity pattern obtained by optical profilometer. The lateral dimension of the cavity (the short side of the trench) is 25 μm. The depth of the trench is 1 μm. (E) The linear transmission spectra obtained by focusing IR beams center at the trenched area on the sample. Two peaks at 1,971 cm^–1 and 1,995 cm^–1 are from the confined cavity, whereas the peak at 2,099 cm^–1 is from the unconfined region. The dashed line is the simulation result.The molecular vibrational polariton-based qubits is a potential platform for quantum simulation with several advantages, such as operating at ambient temperature, ease of tunability of cavities, intrinsic systems for quantum light molecular spectroscopy, and the customizable “designer” vibrational chromophores (35–37). Although similar efforts have been made on exciton polaritons, the single qubit property of the FP cavity has limited the scalability of molecular vibrational polaritons for advancing quantum simulation (34). One way to overcome the limitations is to form multi-qubit systems, also called qudits, using multi-cavity polariton systems. Early work from our group extended the FP cavity into two pairs of polaritons in spatially neighboring cavities (9, 26), which we termed as dual-cavity system herein (Fig. 1B). However, the high-frequency coherences composed of polaritons from different cavity modes (referred as intercavity coherences) cannot survive due to decoherence, because polaritons reside in different spatial locations. To address this limitation, a novel cavity structure is needed to multiplex polariton coherences for simulating complex quantum phenomena.In this work, we overcome the FP cavity limitations and create two cavity modes with distinct energies by applying an orthogonal confinement in FP cavity system. This confinement effect is similar to “particle in a box,” which is widely applied in semiconductor materials (38–45), including quantum dots and wells. Simply put, when the dimensions of a system are close to the wavelength of the particles, only certain wave functions can survive the boundary condition of the spatial confinement, leading to distinct quantum states and tunable energy gaps. However, compared to the confinement effect in semiconductor materials, this phenomenon has not been heavily explored in the IR regime. Here, we implemented confinement to IR cavities to create two photonic modes at a specific in-plane momentum, and we showed that the confined cavity had a discrete dispersion relation with respect to in-plane momentum. We further demonstrated that under VSC conditions, a quadruplet of polaritons (polaritonic qudits) was created which formed coherences between any pairs of polaritons (Fig. 1C). Thus, introducing confinement in a single cavity created a foundation for generating qudits with complex coherence states or even entanglements in the future (46–48). This advance could create a potential platform for quantum light spectroscopy and other quantum science and technology (49, 50). Therefore, this was a valuable step for molecular polaritonic quantum information technology.     

Volatile-consuming reactions fracture rocks and self-accelerate fluid flow in the lithosphere

Hydration and carbonation reactions within the Earth cause an increase in solid volume by up to several tens of vol%, which can induce stress and rock fracture. Observations of naturally hydrated and carbonated peridotite suggest that permeability and fluid flow are enhanced by reaction-induced fracturing. However, permeability enhancement during solid-volume–increasing reactions has not been achieved in the laboratory, and the mechanisms of reaction-accelerated fluid flow remain largely unknown. Here, we present experimental evidence of significant permeability enhancement by volume-increasing reactions under confining pressure. The hydromechanical behavior of hydration of sintered periclase [MgO + H₂O → Mg(OH)₂] depends mainly on the initial pore-fluid connectivity. Permeability increased by three orders of magnitude for low-connectivity samples, whereas it decreased by two orders of magnitude for high-connectivity samples. Permeability enhancement was caused by hierarchical fracturing of the reacting materials, whereas a decrease was associated with homogeneous pore clogging by the reaction products. These behaviors suggest that the fluid flow rate, relative to reaction rate, is the main control on hydromechanical evolution during volume-increasing reactions. We suggest that an extremely high reaction rate and low pore-fluid connectivity lead to local stress perturbations and are essential for reaction-induced fracturing and accelerated fluid flow during hydration/carbonation.

Hydration and carbonation reactions in the crust and mantle transport H₂O and CO₂ from Earth’s surface to the interior and control volatile budgets within the Earth (1–6). These reactions are characterized by solid-volume increase, by up to several tens of vol%, which induces stress that may lead to fracturing (7–10). The driving force of such stress generation is the thermodynamic free energy released when metastable anhydrous/noncarbonate minerals react with fluids (7). The stress generated by the reaction has the potential to cause rock fracture and fragmentation (7, 11–13), thereby increasing the reactive surface area and fluid flow and further accelerating the reactions (7, 8, 14). Such chemical breaking of rocks, or reaction-induced fracturing, appears to be important in driving hydration and carbonation reactions to completion (8, 15, 16) in an otherwise self-limiting process where reaction products can clog pores and suppress fluid flow, thereby hindering the reaction (15, 17).Observations of naturally serpentinized and fractured ultramafic rocks indicate a volume increase of 20 to 60% during hydration reactions (13, 18–20), providing evidence of an accelerated supply of fluids during hydration (Fig. 1 A and B). Natural carbonation of ultramafic rocks is also associated with extensive fracture networks, and reaction-induced fracturing is considered a key process in mineral carbonation (Fig. 1C) (7, 8, 21). Numerical simulations indicate a positive feedback between volume-increasing reaction, fracturing, and fluid flow (10, 22–32). Laboratory experiments partially reproduce fracturing during peridotite carbonation, serpentinization, and periclase hydration (29, 33–36); however, hydrothermal flow-through experiments of peridotite serpentinization and carbonation show a decrease in permeability and deceleration of fluid flow and reaction rate (37–42). Observations of the natural carbonation of serpentinized peridotite indicate the decrease in permeability and reduced fluid flow and reaction rate are a consequence of pore clogging related to carbonation (43). Until now, no experimental studies have shown a clear increase in permeability during expansive fluid–rock reactions under confining pressure. As such, despite their geological and environmental importance, the evolution of expansive fluid–rock reactions remains difficult to predict, owing to the complex hydraulic–chemical–mechanical feedbacks underlying these reactions (15, 16, 44). The processes controlling the self-acceleration or deceleration of these reactions remain largely unknown.Open in a separate windowFig. 1.Reaction-induced fractures related to natural hydration/carbonation. (A) Polygonal block of serpentinite cut by planar lizardite veins, extracted from a serpentinite body, San Andreas Lake, California. (B) Photomicrograph of mesh structure in partly serpentinized peridotite, Redwood City serpentinite, California [crossed-polarized light (61)]. (C) Quartz veins in silica–carbonate rocks (i.e., listvenite, a carbonated ultramafic rock) that occur along the boundaries of serpentinite bodies, San Jose, California. ol, olivine; serp, serpentine (lizardite ± antigorite mixture); br, brucite.Here, we use the hydration of periclase to brucite [MgO + H₂O → Mg(OH)₂] as an analog for solid-volume–increasing reactions in the Earth. This reaction produces an extreme solid-volume increase of 119%, with a high reaction rate at 100 to 600 °C (45). Previous experimental studies on periclase hydration have revealed that extensive fracturing occurs under certain conditions (29, 33, 35), yet the links between fracturing experiments (periclase hydration), nonfracturing experiments (peridotite hydration/carbonation), and natural observations are unknown. On the basis of in situ observations of fluid flow during the reactions, we clearly show that fluid flow and associated permeability are strongly enhanced by solid-volume–increasing reactions under confining pressure (i.e., at simulated depth). Based on the experimental results and nondimensional parameterization, we propose that the ratio of the initial fluid flow rate to the reaction rate has a primary control on the self-acceleration and deceleration of fluid flow and reactions during hydration and carbonation within the Earth.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Chirality-matched catalyst-controlled macrocyclization reactions

Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue to attract great interest due to their important applications in physical, pharmacological, and environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over intermolecular reactions in the ring-closing step is often a key challenge. Furthermore, syntheses of macrocycles with stereogenic elements confer an additional challenge, while access to such macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts can have in promoting efficient macrocyclization reactions. We show that the chirality of the catalyst is essential for promoting favorable, matched transition-state relationships that favor macrocyclization of substrates with preexisting stereogenic elements; curiously, the chirality of the catalyst is essential for successful reactions, even though no new static (i.e., not “dynamic”) stereogenic elements are created. Control experiments involving either achiral variants of the catalyst or the enantiomeric form of the catalyst fail to deliver the macrocycles in significant quantity in head-to-head comparisons. The generality of the phenomenon, demonstrated here with a number of substrates, stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles, presumably through related, catalyst-defined peripheral interactions with their acyclic substrates.

Macrocyclic compounds are known to perform a myriad of functions in the physical and biological sciences. From cyclodextrins that mediate analyte separations (1) to porphyrin cofactors that sit in enzyme active sites (2, 3) and to potent biologically active, macrocyclic natural products (4) and synthetic variants (5–7), these structures underpin a wide variety of molecular functions (Fig. 1A). In drug development, such compounds are highly coveted, as their conformationally restricted structures can lead to higher affinity for the desired target and often confer additional metabolic stability (8–13). Accordingly, there exists an entire synthetic chemistry enterprise focused on efficient formation and functionalization of macrocycles (14–18).Open in a separate windowFig. 1.(A) Examples of macrocyclic compounds with important applications. HCV, hepatitis C virus. (B) Use of chiral ligands in metal-catalyzed or mediated stereoselective macrocyclization reactions. (C) Remote desymmetrization using guanidinylated ligands via Ullmann coupling. (D) This work: use of copper/peptidyl complexes for macrocyclization and the exploration of matched and mismatched effect.In syntheses of macrocyclic compounds, the ring-closing step is often considered the most challenging step, as competing di- and oligomerization pathways must be overcome to favor the intramolecular reaction (14). High-dilution conditions are commonly employed to favor macrocyclization of linear precursors (19). Substrate preorganization can also play a key role in overcoming otherwise high entropic barriers associated with multiple conformational states that are not suited for ring formation. Such preorganization is most often achieved in synthetic chemistry through substrate design (14, 20–22). Catalyst or reagent controls that impose conformational benefits that favor ring formation are less well known. Yet, critical precedents include templating through metal-substrate complexation (23, 24), catalysis by foldamers (25) or enzymes (26–29), or, in rare instances, by small molecules (discussed below). Characterization of biosynthetic macrocyclization also points to related mechanistic issues and attributes for efficient macrocyclizations (30–34). Coupling macrocyclization reactions to the creation of stereogenic elements is also rare (35). Metal-mediated reactions have been applied toward stereoselective macrocyclizations wherein chiral ligands transmit stereochemical information to the products (Fig. 1B). For example, atroposelective ring closure via Heck coupling has been applied in the asymmetric total synthesis of isoplagiochin D by Speicher and coworkers (36–40). Similarly, atroposelective syntheses of (+)-galeon and other diarylether heptanoid natural products were achieved via Ullman coupling using N-methyl proline by Salih and Beaudry (41). Finally, Reddy and Corey reported the enantioselective syntheses of cyclic terpenes by In-catalyzed allylation utilizing a chiral prolinol-based ligand (42). While these examples collectively illustrate the utility of chiral ligands in stereoselective macrocyclizations, such examples remain limited.We envisioned a different role for chiral catalysts when addressing intrinsically disfavored macrocyclization reactions. When unfavorable macrocyclization reactions are confronted, we hypothesized that a catalyst–substrate interaction might provide transient conformational restriction that could promote macrocyclization. To address this question, we chose to explore whether or not a chiral catalyst-controlled macrocyclization might be possible with peptidyl copper complexes. In the context of the medicinally ubiquitous diarylmethane scaffold, we had previously demonstrated the capacity for remote asymmetric induction in a series of bimolecular desymmetrizations using bifunctional, tetramethylguanidinylated peptide ligands. For example, we showed that peptidyl copper complexes were able to differentiate between the two aryl bromides during C–C, C–O, and C–N cross-coupling reactions (Fig. 1C) (43–45). Moreover, in these intermolecular desymmetrizations, a correlation between enantioselectivity and conversion was observed, revealing the catalyst’s ability to perform not only enantiotopic group discrimination but also kinetic resolution on the monocoupled product as the reaction proceeds (44). This latter observation stimulated our speculation that if an internal nucleophile were present to undergo intramolecular cross-coupling to form a macrocycle, stereochemically sensitive interactions (so-called matched and mismatched effects) (46) could be observed (Fig. 1D). Ideally, we anticipated that transition state–stabilizing interactions might even prove decisive in matched cases, and the absence of catalyst–substrate stabilizing interactions might account for the absence of macrocyclization for these otherwise intrinsically unfavorable reactions. Herein, we disclose the explicit observation of these effects in chiral catalyst-controlled macrocyclization reactions.     

Electrochemical borylation of carboxylic acids

A simple electrochemically mediated method for the conversion of alkyl carboxylic acids to their borylated congeners is presented. This protocol features an undivided cell setup with inexpensive carbon-based electrodes and exhibits a broad substrate scope and scalability in both flow and batch reactors. The use of this method in challenging contexts is exemplified with a modular formal synthesis of jawsamycin, a natural product harboring five cyclopropane rings.

Boronic acids are among the most malleable functional groups in organic chemistry as they can be converted into almost any other functionality (1–3). Aside from these versatile interconversions, their use in the pharmaceutical industry is gaining traction, resulting in approved drugs such as Velcade, Ninlaro, and Vabomere (4). It has been shown that boronic acids can be rapidly installed from simple alkyl halides (5–19) or alkyl carboxylic acids through the intermediacy of redox-active esters (RAEs) (Fig. 1A) (20–24). Our laboratory has shown that both Ni (20) and Cu (21) can facilitate this reaction. Conversely, Aggarwal and coworkers (22) and Li and coworkers (23) demonstrated photochemical variations of the same transformation. While these state-of-the-art approaches provide complementary access to alkyl boronic acids, each one poses certain challenges. For example, the requirement of excess boron source and pyrophoric MeLi under Ni catalysis is not ideal. Although more cost-effective and operationally simple, Cu-catalyzed borylation conditions can be challenging on scale due to the heterogeneity resulting from the large excess of LiOH•H₂O required. In addition to its limited scope, Li and coworkers’ protocol requires 4 equivalence of B₂pin₂ and an expensive Ir photocatalyst. The simplicity of Aggarwal and coworkers’ approach is appealing in this regard and represents an important precedent for the current study.Open in a separate windowFig. 1.(A) Prior approaches to access alkyl boronic esters from activated acids. (B) Inspiration for initiating SET events electrochemically to achieve borylation. (C) Summary of this work.At the heart of each method described above, the underlying mechanism relies on a single electron transfer (SET) event to promote decarboxylation and form an alkyl radical species. In parallel, the related borylation of aryl halides via a highly reactive aryl radical can also be promoted by SET. While numerous methods have demonstrated that light can trigger this mechanism (Fig. 1B) (16, 25–31), simple electrochemical cathodic reduction can elicit the same outcome (32–35). It was postulated that similar electrochemically driven reactivity could be translated to alkyl RAEs. The development of such a transformation would be highly enabling, as synthetic organic electrochemistry allows the direct addition or removal of electrons to a reaction, representing an incredibly efficient way to forge new bonds (36–40). This disclosure reports a mild, scalable, and operationally simple electrochemical decarboxylative borylation (Fig. 1C) not reliant on transition metals or stoichiometric reductants. In addition to mechanistic studies of this interesting transformation, applications to a variety of alkyl RAEs, comparison to known decarboxylative borylation methods, and a formal synthesis of the polycyclopropane natural product jawsamycin [(–)-FR-900848] are presented.     

Electrophilic aromatic substitution reactions of compounds with Craig-Möbius aromaticity

Electrophilic aromatic substitution (EAS) reactions are widely regarded as characteristic reactions of aromatic species, but no comparable reaction has been reported for molecules with Craig-Möbius aromaticity. Here, we demonstrate successful EAS reactions of Craig-Möbius aromatics, osmapentalenes, and fused osmapentalenes. The highly reactive nature of osmapentalene makes it susceptible to electrophilic attack by halogens, thus osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene can undergo typical EAS reactions. In addition, the selective formation of a series of halogen substituted metalla-aromatics via EAS reactions has revealed an unprecedented approach to otherwise elusive compounds such as the unsaturated cyclic chlorirenium ions. Density functional theory calculations were conducted to study the electronic effect on the regioselectivity of the EAS reactions.

Aromaticity, a core concept in chemistry, was initially introduced to account for the bonding, stability, reactivity, and other properties of many unsaturated organic compounds. There have been many elaborations and extensions of the concept of aromaticity (1, 2). The concepts of Hückel aromaticity and Möbius aromaticity are widely accepted (Fig. 1A). A π-aromatic molecule of the Hückel type is planar and has 4n + 2 conjugated π-electrons (n = 0 or an integer), whereas a Möbius aromatic molecule has one twist of the π-system, similar to that in a Möbius strip, and 4n π-electrons (3, 4). Since the discovery of naphthalene in 1821, aromatic chemistry has developed into a rich field and with a variety of subdisciplines over the course of its 200-y history, and the concept of aromaticity has been extended to other nontraditional structures with “cyclic delocalization of mobile electrons” (5). For example, benzene-like metallacycles—predicted by Hoffmann et al. as metallabenzenes—in which a metal replaces a C–H group in the benzene ring (6), have garnered extensive research interest from both experimentalists and theoreticians (7–12). As paradigms of the metalla-aromatic family, most complexes involving metallabenzene exhibit thermodynamic stability, kinetic persistence, and chemical reactivity associated with the classical aromaticity concept (13–15). Typically, like benzene, metallabenzene can undergo characteristic reactions of aromatics such as electrophilic aromatic substitution (EAS) reactions (16–18) (Fig. 1B, I) and nucleophilic aromatic substitution reactions (19–21).Open in a separate windowFig. 1.Schematic representations of aromaticity classification (A) and EAS reactions (B) of benzene, metallabenzene, and polycyclic metallacycles with Craig-Möbius aromaticity.The incorporation of transition metals has also led to an increase in the variety of the aromatic families (22–25). We have reported that stable and highly unusual bicyclic systems, metallapentalenes (osmapentalenes), benefit from Craig-Möbius aromaticity (26–30). In contrast to other reported Möbius aromatic compounds with twisted topologies, which are known as Heilbronner-Möbius aromatics (31–34), the involvement of transition metal d orbitals in π-conjugation switches the Hückel anti-aromaticity of pentalene into the planar Craig-Möbius aromaticity of metallapentalene (35–38) (Fig. 1A, III). Both the twisted topology and the planar Craig-Möbius aromaticity are well established and have been accepted as reasonable extensions of aromaticity (39–43). There has been no experimental evidence, however, as to whether these Möbius aromatic molecules can undergo classical aromatic substitution reactions, such as EAS reactions, instead of addition reactions. Given the key role of EAS in aromatic chemistry to obtain various derivatives, we sought to extend the understanding of the reactivity paradigm in the metalla-aromatic family.Our recent synthetic efforts associated with the metallapentalene system prompted us to investigate whether typical EAS reactions could proceed in these Craig-Möbius aromatics. If so, how could substitution be achieved in the same way that it is with traditional Hückel aromatics such as benzenes? In this paper, we present EAS reactions, mainly the halogenation of osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene, which follow the classic EAS mechanistic scheme (Fig. 1B). With the aid of density functional theory (DFT) calculations, we characterized the effects on EAS reactivity and regioselectivity.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Click-to-lead design of a picomolar ABA receptor antagonist with potent activity in vivo

Abscisic acid (ABA) is a key plant hormone that mediates both plant biotic and abiotic stress responses and many other developmental processes. ABA receptor antagonists are useful for dissecting and manipulating ABA’s physiological roles in vivo. We set out to design antagonists that block receptor–PP2C interactions by modifying the agonist opabactin (OP), a synthetically accessible, high-affinity scaffold. Click chemistry was used to create an ∼4,000-member library of C4-diversified opabactin derivatives that were screened for receptor antagonism in vitro. This revealed a peptidotriazole motif shared among hits, which we optimized to yield antabactin (ANT), a pan-receptor antagonist. An X-ray crystal structure of an ANT–PYL10 complex (1.86 Å) reveals that ANT’s peptidotriazole headgroup is positioned to sterically block receptor–PP2C interactions in the 4′ tunnel and stabilizes a noncanonical closed-gate receptor conformer that partially opens to accommodate ANT binding. To facilitate binding-affinity studies using fluorescence polarization, we synthesized TAMRA–ANT. Equilibrium dissociation constants for TAMRA–ANT binding to Arabidopsis receptors range from ∼400 to 1,700 pM. ANT displays improved activity in vivo and disrupts ABA-mediated processes in multiple species. ANT is able to accelerate seed germination in Arabidopsis, tomato, and barley, suggesting that it could be useful as a germination stimulant in species where endogenous ABA signaling limits seed germination. Thus, click-based diversification of a synthetic agonist scaffold allowed us to rapidly develop a high-affinity probe of ABA–receptor function for dissecting and manipulating ABA signaling.

The phytohormone abscisic acid (ABA) controls numerous physiological processes in plants ranging from seed development, germination, and dormancy to responses for countering biotic and abiotic stresses (1). ABA binds to the PYR/PYL/RCAR (Pyrabactin Resistance 1/PYR1-like/Regulatory Component of ABA Receptor) soluble receptor proteins (2, 3) and triggers a conformational change in a flexible “gate” loop flanking the ligand-binding pocket such that the ABA–receptor complex can then bind to and inhibit clade A type II C protein phosphatases (PP2Cs), which normally dephosphorylate and inactivate SNF1-related protein kinase 2 (SnRK2). This, in turn, leads to SnRK2 activation, phosphorylation of downstream targets, and multiple cellular outputs (4, 5).Chemical modulators of ABA perception have been sought as both research tools for dissecting ABA’s role in plant physiology and for their potential agricultural utility (6, 7). Dozens of ABA receptor agonists, which reduce transpiration and water use by inducing guard cell closure, have been developed and are being explored as chemical tools for mitigating the effects of drought on crop yields (7–23), most of them either being analogs of ABA or sulfonamides similar to quinabactin (24). ABA receptor antagonists could conceivably be useful in cases where water is not limiting, for example, to increase transpiration and gas exchange under elevated CO₂ in glasshouse agriculture, as germination stimulators, and for studying the ABA dependence of physiological processes, among other applications (25–31). Thus, both ABA receptor agonists and antagonists have potential uses as research tools and for plant biotechnology.In principle, there are at least two mechanisms for blocking ABA receptor activation: by preventing gate closure, which is necessary for PP2C binding, or by sterically disrupting the activated, closed-gate receptor conformer from binding to PP2Cs. Prior efforts to design antagonists have focused on the latter strategy and include multiple ABA-derived ligands such as AS6 (25), PanMe (26), 3′-alkyl ABA (30–32), 3′-(phenyl alkynyl) ABA (33), or ligands derived from tetralone ABA (34) with varying degrees of conformational restriction (27, 28, 35). With the exception of PanMe, these antagonists have linkers attached to the 3′ carbon of ABA or 11′ carbon of tetralone ABA, which is positioned to disrupt receptor–PP2C interactions by protruding through the 3′ tunnel. PanMe was created by modifying ABA’s C4′ (Fig. 1) with a toluylpropynyl ether substituent designed to occupy the 4′ tunnel, a site of close receptor–PP2C contact (26). Structural studies showed that this 4′ moiety adopts two conformations, one that resides in the 4′ tunnel and another that occupies the adjacent 3′ tunnel (26). Collectively, these elegant studies have demonstrated that antagonists of receptor–PP2C interactions can be designed by modifying agonists at sites situated proximal to the 3′ or 4′ tunnels. Despite these advances, current antagonists have limitations. For example, PanMe, which has low nanomolar affinity for the subfamily II receptor PYL5, is limited by relatively low activity on subfamily I and III ABA receptors, and as we show here, the ABA antagonist AA1 (36) (Fig. 1) lacks detectable antagonist activity in vitro and is, therefore, unlikely to be a true ABA receptor antagonist. Together, these data suggest that higher-affinity pan-antagonists and/or molecules with increased bioavailability will be necessary to more efficiently block endogenous ABA signaling. We set out to address these limitations by modifying the scaffold of the synthetic ABA agonist opabactin (OP), which has an approximately sevenfold increase in both affinity and bioactivity relative to ABA (21). We describe an OP derivative called antabactin (ANT) and show that it is a high-affinity binder and antagonist of ABA receptors that disrupts ABA-mediated signaling in vivo.Open in a separate windowFig. 1.Structures of ABA, PanMe, and AA1.     

Volcanically driven lacustrine ecosystem changes during the Carnian Pluvial Episode (Late Triassic)

The Late Triassic Carnian Pluvial Episode (CPE) saw a dramatic increase in global humidity and temperature that has been linked to the large-scale volcanism of the Wrangellia large igneous province. The climatic changes coincide with a major biological turnover on land that included the ascent of the dinosaurs and the origin of modern conifers. However, linking the disparate cause and effects of the CPE has yet to be achieved because of the lack of a detailed terrestrial record of these events. Here, we present a multidisciplinary record of volcanism and environmental change from an expanded Carnian lake succession of the Jiyuan Basin, North China. New U–Pb zircon dating, high-resolution chemostratigraphy, and palynological and sedimentological data reveal that terrestrial conditions in the region were in remarkable lockstep with the large-scale volcanism. Using the sedimentary mercury record as a proxy for eruptions reveals four discrete episodes during the CPE interval (ca. 234.0 to 232.4 Ma). Each eruptive phase correlated with large, negative C isotope excursions and major climatic changes to more humid conditions (marked by increased importance of hygrophytic plants), lake expansion, and eutrophication. Our results show that large igneous province eruptions can occur in multiple, discrete pulses, rather than showing a simple acme-and-decline history, and demonstrate their powerful ability to alter the global C cycle, cause climate change, and drive macroevolution, at least in the Triassic.

The Carnian Pluvial Episode (CPE; ca. 234 to ∼232 Ma; Late Triassic) was an interval of significant changes in global climate and biotas (1, 2). It was characterized by warming (3, 4) and enhancement of the hydrological cycle (5–7), linked to repeated C isotope fluctuations (8–11) and accompanied by increased rainfall (1), intensified continental weathering (9, 12), shutdown of carbonate platforms (13), widespread marine anoxia (4), and substantial biological turnover (1, 2, 10). Available stratigraphic data indicate that the Carnian climatic changes broadly coincide with, and could have been driven by, the emplacement of the Wrangellia large igneous province (LIP) (2, 4, 7, 8, 10, 14, 15) (Fig. 1A). It is postulated that the voluminous emission of volcanic CO₂, with consequent global warming and enhancement of a mega-monsoonal climate, was responsible for the CPE (9, 16), although the link is imprecise (2, 17) because the interval of Wrangellian eruptions have not yet been traced in the sedimentary records encompassing the CPE.Open in a separate windowFig. 1.Location and geological context for the study area. (A) Paleogeographic reconstruction for the Carnian (∼237 to 227 Ma) Stage (Late Triassic), showing locations of the study area and volcanic centers (revised after ref. 4, with volcanic data from refs. 4, 7, 49, and 50). (B) Tectono-paleogeographic map of the NCP during the Late Triassic (modified from ref. 21), showing the location of the study area. (C) Stratigraphic framework of the Upper Chunshuyao Formation (CSY) to the Lower Yangshuzhuang (YSZ) Formation from the Jiyuan Basin (modified from ref. 20). Abbreviations: LIP, Large Igneous Province; QDOB, Qingling-Dabie Orogenic Belt; S-NCP, southern NCP; SCP, South China Plate; Fm., Formation; m & s, coal, mudstone, and silty mudstone; s., sandstone; c, conglomerate; Dep. env., Depositional environment; and C.-P., Coniopteris-Phoenicopsis.The CPE was originally identified because of changes in terrestrial sedimentation, but most subsequent studies have been on marine strata (2, 4, 7–10). By contrast, much less is known about the effects of this climatic episode on terrestrial environments (2), although there were major extinctions and radiations among animals (including dinosaurs, crocodiles, turtles, and the first mammals and insects) and modern conifer families (2). Some of the new organisms may have flourished because of the spread of humid environments, such as the turtles and metoposaurids (18, 19).In this study, we have investigated terrestrial sediments from the Zuanjing-1 (ZJ-1) borehole in the Jiyuan Basin of the southern North China Plate (NCP) and use zircon U–Pb ages from two tuffaceous claystone horizons, fossil plant biostratigraphy, and organic C isotope (δ¹³C_org) and Hg chemostratigraphy to identify the CPE and volcanic activity.     

Opacity and conductivity measurements in noble gases at conditions of planetary and stellar interiors

The noble gases are elements of broad importance across science and technology and are primary constituents of planetary and stellar atmospheres, where they segregate into droplets or layers that affect the thermal, chemical, and structural evolution of their host body. We have measured the optical properties of noble gases at relevant high pressures and temperatures in the laser-heated diamond anvil cell, observing insulator-to-conductor transformations in dense helium, neon, argon, and xenon at 4,000–15,000 K and pressures of 15–52 GPa. The thermal activation and frequency dependence of conduction reveal an optical character dominated by electrons of low mobility, as in an amorphous semiconductor or poor metal, rather than free electrons as is often assumed for such wide band gap insulators at high temperatures. White dwarf stars having helium outer atmospheres cool slower and may have different color than if atmospheric opacity were controlled by free electrons. Helium rain in Jupiter and Saturn becomes conducting at conditions well correlated with its increased solubility in metallic hydrogen, whereas a deep layer of insulating neon may inhibit core erosion in Saturn.Noble gases play important roles in the evolution and dynamics of planets and stars, especially where they appear in a condensed, purified state. In gas giant planets, helium and neon can precipitate as rain in metallic hydrogen envelopes, leading to planetary warming and specifically the anomalously slow cooling of Saturn (1–8). In white dwarf stars cooling can be especially fast due to the predicted low opacity of dense helium atmospheres, affecting the calibration of these objects as cosmological timekeepers (9–12). In these systems, the transformation of dense noble gases (particularly He) from optically transparent insulators to opaque electrical conductors is of special importance (2, 9, 11, 12).Dense noble gases are expected to show systematic similarities in their properties at extreme conditions (13–17); however, a general understanding of their insulator–conductor transformation remains to be established. Xe is observed to metallize near room temperature under pressures similar to those at Earth’s core–mantle boundary (18, 19). Ar and He are observed to conduct only at combined high pressure and temperature (12, 13, 17). Ne is predicted to have the highest metallization pressure of all known materials—10³ times that of Xe and 10 times that of He (14, 18, 20, 21)—and has never been documented outside of its insulating state. Experimental probes of extreme densities and temperatures in noble gases have previously relied on dynamic compression by shock waves (12, 13, 17, 22–24). However, in such adiabatic experiments, light and compressible noble gases heat up significantly and can ultimately reach density maxima (12, 13, 17, 21, 24, 25), so that conditions created often lie far from those deep within planets (7, 8) and stars (9).Here we report experiments in the laser-heated diamond anvil cell (15, 16, 26–29) on high-density and high-temperature states of the noble gases Xe, Ar, Ne, and He (Fig. 1). Rapid heating and cooling of compressed samples using pulsed laser heating (26, 27) is coupled with time domain spectroscopy of thermal emission (26) to determine sample temperature and transient absorption to establish corresponding sample optical properties (Figs. S1 and S2). A sequence of heat cycles to increasing temperature documents optical changes in these initially transparent insulators.Open in a separate windowFig. 1.Creating and probing extreme states of noble gases. (A) Configuration of laser heating and transient absorption probing of the diamond anvil cell, with probe beams transmitted through the cell into the detection system. (B) Microscopic view of the diamond cell cavity, which contains a noble gas sample and a metal foil (Ir) which converts laser radiation to heat and has small hole at the heated region through which probe beams are transmitted to test optical character of samples. (C) Finite element model (26) (Fig. S3) of the temperature distribution in heated Ar at 51 GPa (Fig. 2), with solid–melt (16) and insulator–conductor (α = 0.1 μm⁻¹) boundaries in the sample marked dashed and dotted, respectively. (D) Schematic of time domain probing during transient heating. Temperature is determined from thermal emission (red) and absorption from transmitted probe beams: a continuous laser (cw; green) and pulsed supercontinuum broadband (bb; blue).     

Prediction errors disrupt hippocampal representations and update episodic memories

The brain supports adaptive behavior by generating predictions, learning from errors, and updating memories to incorporate new information. Prediction error, or surprise, triggers learning when reality contradicts expectations. Prior studies have shown that the hippocampus signals prediction errors, but the hypothesized link to memory updating has not been demonstrated. In a human functional MRI study, we elicited mnemonic prediction errors by interrupting familiar narrative videos immediately before the expected endings. We found that prediction errors reversed the relationship between univariate hippocampal activation and memory: greater hippocampal activation predicted memory preservation after expected endings, but memory updating after surprising endings. In contrast to previous studies, we show that univariate activation was insufficient for understanding hippocampal prediction error signals. We explain this surprising finding by tracking both the evolution of hippocampal activation patterns and the connectivity between the hippocampus and neuromodulatory regions. We found that hippocampal activation patterns stabilized as each narrative episode unfolded, suggesting sustained episodic representations. Prediction errors disrupted these sustained representations and the degree of disruption predicted memory updating. The relationship between hippocampal activation and subsequent memory depended on concurrent basal forebrain activation, supporting the idea that cholinergic modulation regulates attention and memory. We conclude that prediction errors create conditions that favor memory updating, prompting the hippocampus to abandon ongoing predictions and make memories malleable.

In daily life, we continuously draw on past experiences to predict the future. Expectation and surprise shape learning across many situations, such as when we discover misinformation in the news, receive feedback on an examination, or make decisions based on past outcomes. When our predictions are incorrect, we must update our mnemonic models of the world to support adaptive behavior. Prediction error is a measure of the discrepancy between expectation and reality; this surprise signal is both evident in brain activity and related to learning (1–6). The brain dynamically reconstructs memories during recall, recreating and revising past experiences based on current information (7). The intuitive idea that surprise governs learning has long shaped our understanding of memory, reward learning, perception, action, and social behavior (2, 8–14). Yet, the neural mechanisms that allow prediction error to update memories remain unknown.Past research has implicated the hippocampus in each of the mnemonic functions required for learning from prediction errors: retrieving memories to make predictions, identifying discrepancies between past and present, and encoding new information (2, 15–20). Functional MRI (fMRI) studies have shown that hippocampal activation increases after predictions are violated; this surprise response has been termed “mismatch detection” (18, 19, 21–23) or “mnemonic prediction error” (20). These past studies have shown that the hippocampus detects mnemonic prediction errors. Several theoretical frameworks have hypothesized that this hippocampal prediction error signal could update memories (17, 20, 24–27), but this crucial link for understanding how we learn from error has not yet been demonstrated.What mechanisms could link hippocampal prediction errors to memory updating? A leading hypothesis is that prediction errors shift the focus of attention and adjust cognitive processing (20, 28–32). After episodes that align with expectations, we should continue generating predictions and shift attention internally, sustaining and reinforcing existing memories. However, after mnemonic prediction errors, we should reset our expectations and shift attention externally, preparing to encode new information and update memories. Consistent with this idea, mnemonic prediction errors have been shown to enhance the hippocampal input pathway that supports encoding, but suppress the output pathway that supports retrieval (20). We propose that surprising events may also change intrinsic hippocampal processing, changing the effect of hippocampal activation on memory outcomes.Neuromodulation may be a critical factor that regulates hippocampal processing and enables memory updating. Currently, there is mixed evidence supporting two hypotheses: acetylcholine or dopamine could act upon the hippocampus to regulate processing after surprising events (24–27, 29, 31, 33, 34). Several models have proposed that acetylcholine from the medial septum (within the basal forebrain) regulates the balance between input and output pathways in the hippocampus (27–29, 35–38), thus allowing stored memories to be compared with perceptual input (31, 38, 39). After prediction errors, acetylcholine release could change hippocampal processing and enhance encoding or memory updating (26, 29, 33, 37, 39). On the other hand, dopamine released from the ventral tegmental area (VTA), if transmitted to the hippocampus, could also modulate hippocampal plasticity after prediction errors. Past studies have shown that the hippocampus and VTA are coactivated after surprising events (40, 41). Other work has shown that coactivation of the hippocampus and VTA predicts memory encoding and integration (42–45). Overall, basal forebrain and VTA neuromodulation are both candidate mechanisms for regulating hippocampal processing and memory updating.In the present study, we used an fMRI task with human participants to examine trial-wise hippocampal responses to prediction errors during narrative videos. During the “encoding phase,” participants viewed 70 full-length videos that featured narrative episodes with salient endings (e.g., a baseball batter hitting a home run) (Fig. 1A). During the “reactivation phase” the following day, participants watched the videos again (Fig. 1B). We elicited mnemonic prediction errors by interrupting half of the videos immediately before the expected narrative ending (e.g., the video ends while the baseball batter is midswing). These surprising interruptions were comparable to the prediction errors employed in prior studies of memory updating (1). Half of the videos were presented in full-length form (Full, as previously seen during the encoding phase) and half were presented in interrupted form (Interrupted, eliciting prediction error).Open in a separate windowFig. 1.Overview of experimental paradigm. (A) During the encoding phase, all videos were presented in full-length form. Here we show example frames depicting a stimulus video. (B) During the reactivation phase, participants viewed the 70 videos again, but half (35 videos) were interrupted to elicit mnemonic prediction error. Participants were cued with the video name, watched the video (Full or Interrupted), and then viewed a fixation screen. The “baseball” video was interrupted when the batter was midswing. fMRI analyses focused on the postvideo fixation periods (red highlighted boxes). Thus, visual and auditory stimulation were matched across Full and Interrupted conditions, allowing us to compare postvideo neural activation while controlling for perceptual input. (C) During the test phase, participants answered structured interview questions about all 70 videos, and were instructed to answer based on their memory of the Full video originally shown during the Encoding phase. Here we show example text illustrating the memory test format and scoring of correct details (our measure of memory preservation) and false memories (our measure of memory updating, because false memories indicate that the memory has been modified). The void response (“I don’t remember”) is not counted as a false memory. (D) Overview of the experiment. All participants completed encoding, reactivation, and test phases of the study. The Delayed group (fMRI participants) completed the test phase 24 h after reactivation, because prior studies have shown that memory updating becomes evident only after a delay (e.g., to permit protein synthesis). The Immediate group completed the test phase immediately after reactivation and was not scanned. The purpose of the Immediate group was to test the behavioral prediction that memory updating required a delay.During the “test phase,” participants completed a memory test in the form of a structured interview (Fig. 1C). On each trial, participants were cued with the name of the video and recalled the narrative. The experimenter then probed for further details with predetermined questions (e.g., “Can you describe the baseball batter’s ethnicity, age range, or clothing?”). Our critical measure of memory updating was “false memories,” because the presence of a false memory indicates that the original memory was changed in some way. Although it can be adaptive to update real-world memories by incorporating relevant new information, we expected that our laboratory paradigm would induce false memories because participants would integrate interfering details across similar episodes (1, 7). Because we were interested in false memories as a measure of memory updating, we instructed participants not to guess and permitted them to skip details they could not recall.Prior research in human and animals has shown that some memory-updating effects only emerge after delays that allow protein synthesis to occur during consolidation and reconsolidation (1, 46–48). Therefore, to test our primary question about the neural correlates of memory updating, fMRI participants completed the encoding, reactivation, and test phases over 3 d, with 24-h between each session (Delayed group, n = 24). In addition, we tested the behavioral prediction that memory updating would require a delay (i.e., because transforming a memory trace requires protein synthesis) by recruiting a separate group of participants who completed the test phase immediately after the reactivation phase on day 2 (Immediate group, n = 24) (Fig. 1D). Delayed group participants completed the reactivation phase while undergoing an fMRI scan, whereas Immediate group participants (n = 24) were not scanned. Our primary fMRI analyses examined the fixation period immediately following the offset of Full and Interrupted videos (postvideo period) (Fig. 1 B, Right) during the reactivation phase in the Delayed group. Importantly, this design compares neural responses to surprising and expected video endings while controlling for visual and auditory input.Our approach allowed us to test several questions set up by the prior literature. First, we used naturalistic video stimuli to examine the effect of mnemonic prediction error on hippocampal activation and episodic memories. Second, to investigate hippocampal processing, we used multivariate analyses to track how episodic representations were sustained or disrupted over time. Third, to test hypotheses about neuromodulatory mechanisms, we related hippocampal activation and memory updating to activation in the basal forebrain and VTA.     

Foveal analysis and peripheral selection during active visual sampling

Human vision is an active process in which information is sampled during brief periods of stable fixation in between gaze shifts. Foveal analysis serves to identify the currently fixated object and has to be coordinated with a peripheral selection process of the next fixation location. Models of visual search and scene perception typically focus on the latter, without considering foveal processing requirements. We developed a dual-task noise classification technique that enables identification of the information uptake for foveal analysis and peripheral selection within a single fixation. Human observers had to use foveal vision to extract visual feature information (orientation) from different locations for a psychophysical comparison. The selection of to-be-fixated locations was guided by a different feature (luminance contrast). We inserted noise in both visual features and identified the uptake of information by looking at correlations between the noise at different points in time and behavior. Our data show that foveal analysis and peripheral selection proceeded completely in parallel. Peripheral processing stopped some time before the onset of an eye movement, but foveal analysis continued during this period. Variations in the difficulty of foveal processing did not influence the uptake of peripheral information and the efficacy of peripheral selection, suggesting that foveal analysis and peripheral selection operated independently. These results provide important theoretical constraints on how to model target selection in conjunction with foveal object identification: in parallel and independently.Almost all human visually guided behavior relies on the selective uptake of information, due to sensory and cognitive limitations. On the sensory side, the sampling of visual input by the retinal mosaic of photoreceptors becomes increasingly sparse and irregular away from central vision (1). In addition, fewer cortical neurons are devoted to the analysis of peripheral visual information (cortical magnification) (2, 3). Humans and other animals with so-called foveated visual systems have evolved gaze-shifting mechanisms to overcome these limitations. Saccadic eye movements serve to rapidly and efficiently deploy gaze to objects and regions of interest in the visual field. Sampling the environment appropriately with gaze is the starting point of adaptive visual-motor behavior (4, 5).Studies have shown that saccadic eye movements are guided by analysis of information in the visual periphery up to 80–100 ms before saccade execution (6–8). However, active vision typically requires humans not only also to analyze information in the visual periphery to decide where to fixate next (peripheral selection), but also to analyze the information at the current fixation location (foveal analysis). Not much is known about how foveal analysis and peripheral selection are coordinated and interact. In this regard, we need to know (i) whether and to what extent foveal analysis and peripheral selection are constrained by a common bottleneck or limited capacity resource, and (ii) how time within a fixation is allocated to these two tasks.Capacity limitations are ubiquitous in human visual processing. There is a long-standing debate on the extent to which visual attention may be focused on different locations in the visual field (9–11). If foveal analysis and peripheral selection both require a spatial attentional “spotlight,” the coordination of these two tasks will be constrained by the way in which this spotlight can be configured. For example, the size of the spotlight may vary with the processing difficulty of foveal information, as in tunnel vision (12, 13). Similarly, in both reading (14) and scene-viewing (15), a reduction in the perceptual span has been reported with higher foveal load. A high foveal processing load can also prevent distraction from irrelevant visual information in the periphery (16). These findings suggest that there may be interactions between foveal analysis and peripheral selection (17, 18), in that the gain on peripheral information processing may vary according to the foveal processing load.A useful way to think of the coordination between foveal analysis and peripheral selection is to picture the temporal profile of information extraction over the course of a fixation period. Fig. 1 shows some schematic profiles, or integration windows, for foveal and peripheral information (shown in black and gray respectively). Fig. 1 A–C chart the progression in the extent to which the extraction of peripheral visual information is contingent upon the completion of foveal analysis—from completely contingent (Fig. 1A, serial), through partly contingent (Fig. 1B, cascaded), to completely parallel (Fig. 1C). This temporal relation between foveal analysis and peripheral selection is a core assumption of models of eye movement control in reading (14, 19–21) and other visual-motor domains (22, 23). Finally, Fig. 1D demonstrates a hypothetical tradeoff between an increase in foveal load and a decreased peripheral gain. In this example, the foveal integration window is extended to reflect the higher processing load. The duration of the peripheral window is also extended, but by a smaller amount, and its amplitude is reduced. Note that the accuracy of peripheral selection will be determined by both the amplitude and the duration of the integration window.Open in a separate windowFig. 1.Hypothetical temporal weighting functions for foveal analysis and peripheral selection. (A) Strict serial model: peripheral information is analyzed only once foveal processing is complete. (B) A weaker version of the serial model in which peripheral information is processed once some criterion amount of foveal analysis is complete. (C) Parallel model in which foveal analysis and peripheral selection start together. In A–C, the time window for peripheral selection is shorter than that for foveal analysis, reflecting the primary importance of the latter. (D) Manipulation of foveal load. As foveal processing difficulty is increased, more time is taken to analyze the foveal information. The time window for peripheral selection extends as well, but by a smaller amount. In addition, the gain of peripheral processing is lower, resulting in attenuation of the amplitude of the weighting function.A potentially powerful way to identify the coordination between foveal analysis and peripheral selection is then to estimate these underlying integration windows directly, under conditions of variable foveal processing load. Identifying these windows is far from trivial; it involves determining what information is being processed, from where, and at what point in time during an individual fixation. We have developed a dual-task noise classification approach (24–26) that allows us to identify what information is used by the observer for what “task” over the brief time scale of a single fixation. Using this method, we show that the uptake of information for foveal analysis and peripheral selection proceeds independently and in parallel.     

Coevolution can reverse predator–prey cycles

A hallmark of Lotka–Volterra models, and other ecological models of predator–prey interactions, is that in predator–prey cycles, peaks in prey abundance precede peaks in predator abundance. Such models typically assume that species life history traits are fixed over ecologically relevant time scales. However, the coevolution of predator and prey traits has been shown to alter the community dynamics of natural systems, leading to novel dynamics including antiphase and cryptic cycles. Here, using an eco-coevolutionary model, we show that predator–prey coevolution can also drive population cycles where the opposite of canonical Lotka–Volterra oscillations occurs: predator peaks precede prey peaks. These reversed cycles arise when selection favors extreme phenotypes, predator offense is costly, and prey defense is effective against low-offense predators. We present multiple datasets from phage–cholera, mink–muskrat, and gyrfalcon–rock ptarmigan systems that exhibit reversed-peak ordering. Our results suggest that such cycles are a potential signature of predator–prey coevolution and reveal unique ways in which predator–prey coevolution can shape, and possibly reverse, community dynamics.Population cycles, e.g., predator–prey cycles, and their ecological drivers have been of interest for the last 90 y (1–4). Classical models of predator–prey systems, developed first by Lotka (5) and Volterra (6), share a common prediction: Prey oscillations precede predator oscillations by up to a quarter of the cycle period (7). When plotted in the predator–prey phase plane, these cycles have a counterclockwise orientation (4). These cycles are driven by density-dependent interactions between the populations. When predators are scarce, prey increase in abundance. As their food source increases, predators increase in abundance. When the predators reach sufficiently high densities, the prey population is driven down to low numbers. With a scarcity of food, the predator population crashes and the cycle repeats.While many cycles, like the classic lynx–hare cycles (Fig. 1A) (3), exhibit the above characteristics, predator–prey cycles with different characteristics have also been observed. For example, antiphase cycles where predator oscillations lag behind prey oscillations by half of the cycle period (Fig. 1B) (8) and cryptic cycles where the predator population oscillates while the prey population remains effectively constant (Fig. 1C) (9) have been observed in experimental systems. This diversity of cycle types motivates the question, “Why do cycle characteristics differ across systems?”Open in a separate windowFig. 1.Examples of different kinds of predator–prey cycles. (A) Counterclockwise lynx–hare cycles (3). (B) Antiphase rotifer–algal cycles (8). (C) Cryptic phage-bacteria cycles (9). In all time series, red and blue correspond to predator and prey, respectively. See SI Text, section C for data sources.In Lotka–Volterra and other ecological models, predator and prey life history traits are assumed to be fixed. However, empirical studies across taxa have shown that prey (9–16) and predators (17–20) can evolve over ecological time scales. That is, changes in allele frequencies (and associated phenotypes) can occur at the same rate as changes in population densities or spatial distributions and alter the ecological processes driving the changes in population densities or distributions; this phenomenon has been termed “eco-evolutionary dynamics” (21, 22). Furthermore, predator–prey coevolution is important for driving community composition and dynamics (16, 19, 20, 23–26). This body of work suggests that the interaction between ecological and evolution processes has the potential to alter the ecological dynamics of communities.Experimental (8, 9, 13, 14) and theoretical studies (13, 27, 28) have shown that prey or predator evolution alone can alter the characteristics of predator–prey cycles and drive antiphase (Fig. 1B) and cryptic (Fig. 1C) cycles. Additional theoretical work has shown that predator–prey coevolution can also drive antiphase and cryptic cycles (29). Thus, evolution in one or both species is one mechanism through which antiphase or cryptic predator–prey cycles can arise. However, it is unclear if coevolution can drive additional kinds of cycles with characteristics different from those in Fig. 1.The main contribution of this study is to show that predator–prey coevolution can drive unique cycles where peaks in predator abundance precede peaks in prey abundance, the opposite of what is predicted by classical ecological models. We refer to these reversed cycles as “clockwise cycles.” The theoretical and empirical finding of clockwise cycles represents an example of how evolution over ecological time scales can alter community-level dynamics.     

Attention searches nonuniformly in space and in time

Difficult search tasks are known to involve attentional resources, but the spatiotemporal behavior of attention remains unknown. Are multiple search targets processed in sequence or in parallel? We developed an innovative methodology to solve this notoriously difficult problem. Observers performed a difficult search task during which two probes were flashed at varying delays. Performance in reporting probes at each location was considered a measure of attentional deployment. By solving a second-degree equation, we determined the probability of probe report at the most and least attended probe locations on each trial. Because these values differed significantly, we conclude that attention was focused on one stimulus or subgroup of stimuli at a time, and not divided uniformly among all search stimuli. Furthermore, this deployment was modulated periodically over time at ∼7 Hz. These results provide evidence for a nonuniform spatiotemporal deployment of attention during difficult search.Visual search tasks (e.g., to find a target embedded among similar looking distracters) have long been used to investigate the deployment of attention (1–6). Certain tasks are performed “efficiently,” in which case the search time and accuracy are independent of the number of distracters. Other tasks are more difficult, or “inefficient,” characterized by an increase in reaction times (RTs) and/or a decrease in accuracy with the number of distracting elements, a result typically attributed to the need to allocate attention (4–7). For more than 30 y now, since the pioneering study of Treisman and Gelade in 1980 (4), two opposing theories of attention deployment during difficult search have persisted. Attention could either be allocated nonuniformly to the stimuli, such that in some cases it would switch sequentially from one stimulus (or group of stimuli) to another (4, 5), or be divided uniformly to process all of the stimuli in parallel, but with a drop in efficiency for increasing distractor numbers (2, 8–10). To date, neither of these two theories has been unequivocally disproved. Overall performance in the search task itself is not directly informative, because both theories predict an increase in RT with the number of distracters (11, 12). One alternative is to use briefly flashed probes to test for the deployment of attention at a specific location and time. With two probes, it should be possible to differentiate parallel and sequential processing strategies: The strict parallel theory predicts that both probes should receive equal amounts of attention, whereas the sequential theory predicts that one of the probes will receive more attention than the other. Of course, the most attended probe may not be the same one on every trial, but a simple mathematical manipulation, the solution of a quadratic equation, allows us to access this information despite the need to average performance over trials.In recent years, a second, related, debate has arisen in the literature concerning the temporal behavior of attention. It has been proposed that attention samples visual stimuli periodically rather than continuously (13–18). This question is connected to the uniform vs. nonuniform debate in that the nonuniform (or sequential) model of attention processing maps rather naturally onto a periodic sampling of visual information (with the periodicity reflecting the switching between stimuli). No such relation exists for the parallel uniform model, making it more naturally compatible with continuous processing (although, of course, not incompatible with periodic sampling arising for independent reasons).Consequently, in this study, we asked whether attention processing during a difficult search task is uniform or nonuniform, both in space and in time. We used a difficult (attention demanding) visual search task consisting of finding a letter T among letter L’s (four stimuli). After a varying delay, we probed two of the four stimulus locations (Fig. 1) and computed performance in reporting both probes correctly (PBOTH) or none of the probes correctly (PNONE). Using the mathematical manipulation described in Methods, we were able to determine that attention was not divided equally between the four search item positions, but focused on one stimulus or subgroup of stimuli at a time. Moreover, we found that the deployment of attention was modulated periodically at theta frequency (∼7 Hz). We conclude that in this difficult search task, attention was deployed nonuniformly both in space and in time.Open in a separate windowFig. 1.Experimental procedure. One second to 2 s after pressing the space bar, the search array appears for 30–200 ms depending on the randomly chosen SOA for this trial. Observers report the presence or absence of the target stimulus T among distracting L letters. After the variable SOA (from 30–450 ms relative to search array onset), two probe letters appear randomly for 80 ms at two of the four search array locations. For probe onset SOAs greater than 200 ms, an additional empty screen is presented between the search task and the probe detection task (the fixation point is maintained). In other words, if the SOA was shorter than 200 ms, the interstimulus interval (ISI) was zero; otherwise, the ISI was greater than zero. Masks follow probe stimuli for 200 ms. After mask offset, observers first report the presence or absence of the T among L’s, and then the identity of the two probe stimuli by selecting letters from a list, using the computer mouse. A trial ends when observers click on the end button.     

Age-related changes in working memory and the ability to ignore distraction

A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.The number of items that can be held in working memory (WM) declines with increasing age (1). Our ability to effectively exclude distractors is one basis for this limited working memory capacity (WMC) (2, 3), with impaired inhibitory processing of distraction contributing to an age-related reduction in WM performance (4). A specific impairment in suppressing distractor representations in older adults has been linked to reduced WMC (5). Typically distractors are presented either with the items to be remembered (encoding distraction, ED, e.g., 6, 7) or while these items are held in mind (delay distraction, DD, e.g., 5, 8). We recently highlighted a distinction between the effects of these two types of distraction in younger adults (9). Although greater WMC is associated with an enhanced ability to exclude distractors in both cases, each makes a unique contribution to WMC (9). Here we examine the well-known age-related reduction in WMC. Previous work has identified an age-related delay in ED filtering (7) and an early age-related deficit in DD suppression (8). We directly compare the age-related decline in ED and DD to assess whether an ability to ignore a distraction at encoding or at delay provides the best predictor of general WMC.We obtained data from 29,631 users of a smartphone game (part of The Great Brain Experiment, www.thegreatbrainexperiment.com), a platform that has enabled us to replicate a range of laboratory studies (9, 10). Using this medium we implemented a WM task to enable us to directly compare the effects of age on WM in the absence of distractors (no distraction, ND; Fig. 1A), when distractors are presented at encoding (ED; Fig. 1B) and when distractors are presented during maintenance (DD; Fig. 1C). This large subject pool enabled us to consider data from six age groups (18–24 y: n = 7,658; 25–29 y: n = 5,702; 30–39 y: n = 8,225; 40–49 y: n = 4,667; 50–59 y: n = 2,359; and 60–69 y: n = 1,020). For each condition the number of items to be remembered (WM load) increased as a function of performance until either eight trials had been completed or a participant failed two successive trials of a given WM load. Data were excluded from participants who failed a “load 2” trial in any condition. For each condition, the participant’s score represents the maximum number of items for which they could report all items successfully, representing their WMC.Open in a separate windowFig. 1.The smartphone game. Red circles are presented simultaneously, followed by a delay of 1 s. Participants should then indicate the positions of the red circles. (A) No distraction (ND) condition; only red circles are shown. (B) Encoding distraction (ED) condition; two yellow circles (distractors) are presented with the red circles. (C) Delay distraction (DD) condition; two yellow circles (distractors) are presented during the delay.     

Conjugated polymers based on metalla-aromatic building blocks

Conjugated polymers usually require strategies to expand the range of wavelengths absorbed and increase solubility. Developing effective strategies to enhance both properties remains challenging. Herein, we report syntheses of conjugated polymers based on a family of metalla-aromatic building blocks via a polymerization method involving consecutive carbyne shuttling processes. The involvement of metal d orbitals in aromatic systems efficiently reduces band gaps and enriches the electron transition pathways of the chromogenic repeat unit. These enable metalla-aromatic conjugated polymers to exhibit broad and strong ultraviolet–visible (UV–Vis) absorption bands. Bulky ligands on the metal suppress π–π stacking of polymer chains and thus increase solubility. These conjugated polymers show robust stability toward light, heat, water, and air. Kinetic studies using NMR experiments and UV–Vis spectroscopy, coupled with the isolation of well-defined model oligomers, revealed the polymerization mechanism.

Conjugated polymers are macromolecules usually featuring a backbone chain with alternating double and single bonds (1–3). These characteristics allow the overlapping p-orbitals to form a system with highly delocalized π-electrons, thereby giving rise to intriguing chemical and physical properties (4–6). They have exhibited many applications in organic light-emitting diodes, organic thin film transistors, organic photovoltaic cells, chemical sensors, bioimaging and therapies, photocatalysis, and other technologies (7–10). To facilitate the use of solar energy, tremendous efforts have been devoted in recent decades to developing previously unidentified conjugated polymers exhibiting broad and strong absorption bands (11–13). The common strategies for increasing absorption involve extending π-conjugation by incorporating conjugated cyclic moieties, especially fused rings; modulating the strength of intramolecular charge transfer between donor and acceptor units (D–A effect); increasing the coplanarity of π conjugation through weak intramolecular interactions (e.g., hydrogen bonds); and introducing heteroatoms or heavy atoms into the repeat units of conjugated polymers (11–16). Additionally, appropriate solubility is a prerequisite for processing and using polymers and is usually achieved with the aid of long alkyl or alkoxy side chains (12, 17).Aromatic rings are among the most important building blocks for conjugated polymers. In addition to aromatic hydrocarbons, a variety of aromatic heterocycles composed of main-group elements have been used as fundamental components. These heteroatom-containing conjugated polymers show unique optical and electronic properties (4–10). However, while metalla-aromatic systems bearing a transition metal have been known since 1979 due to the pioneering work by Thorn and Hoffmann (18), none of them have been used as building blocks for conjugated polymers. The HOMO–LUMO gaps (E_g) of metalla-aromatics are generally narrower (Fig. 1) than those of their organic counterparts (19–22). We reasoned that this feature should broaden the absorption window if polymers stemming from metalla-aromatics are achievable.Open in a separate windowFig. 1.Comparison of traditional organic skeletons with metalla-aromatic building blocks (the computed energies are in eV). (A) HOMO–LUMO gaps of classic aromatic skeletons. (B) Carbolong frameworks as potential building blocks for novel conjugated polymers with broad absorption bands and improved solubility.In recent years, we have reported a series of readily accessible metal-bridged bicyclic/polycyclic aromatics, namely carbolong complexes, which are stable in air and moisture (23–25). The addition of osmium carbynes (in carbolong complexes) and alkynes gave rise to an intriguing family of d_π–p_π conjugated systems, which function as excellent electron transport layer materials in organic solar cells (26, 27). These observations raised the following question: Can this efficient addition reaction be used to access metalla-aromatic conjugated polymers? It is noteworthy that incorporation of metalla-aromatic units into conjugated polymers is hitherto unknown. In this contribution, we disclose a polymerization reaction involving M≡C analogs of C≡C bonds, which involves a unique carbyne shuttling strategy (Fig. 2A). This led to examples of metalla-aromatic conjugated polymers (polycarbolongs) featuring metal carbyne units in the main chain. On the other hand, the development of polymerization reactions plays a crucial role in involving certain building blocks in conjugated polymers (28–32). These efficient, specific, and feasible polymerizations could open an avenue for the synthesis of conjugated polymers.Open in a separate windowFig. 2.Design of polymers and synthesis of monomers. (A) Schematic illustration of the polymerization strategy. (B) Preparation of carbolong monomers. Insert: X-ray molecular structure for the cations of complex 3. Ellipsoids are shown at the 50% probability level; phenyl groups in PPh₃ are omitted for clarity.     

Emerging predictable features of replicated biological invasion fronts

Biological dispersal shapes species’ distribution and affects their coexistence. The spread of organisms governs the dynamics of invasive species, the spread of pathogens, and the shifts in species ranges due to climate or environmental change. Despite its relevance for fundamental ecological processes, however, replicated experimentation on biological dispersal is lacking, and current assessments point at inherent limitations to predictability, even in the simplest ecological settings. In contrast, we show, by replicated experimentation on the spread of the ciliate Tetrahymena sp. in linear landscapes, that information on local unconstrained movement and reproduction allows us to predict reliably the existence and speed of traveling waves of invasion at the macroscopic scale. Furthermore, a theoretical approach introducing demographic stochasticity in the Fisher–Kolmogorov framework of reaction–diffusion processes captures the observed fluctuations in range expansions. Therefore, predictability of the key features of biological dispersal overcomes the inherent biological stochasticity. Our results establish a causal link from the short-term individual level to the long-term, broad-scale population patterns and may be generalized, possibly providing a general predictive framework for biological invasions in natural environments.What is the source of variance in the spread rates of biological invasions? The search for processes that affect biological dispersal and sources of variability observed in ecological range expansions is fundamental to the study of invasive species dynamics (1–10), shifts in species ranges due to climate or environmental change (11–13), and, in general, the spatial distribution of species (3, 14–16). Dispersal is the key agent that brings favorable genotypes or highly competitive species into new ranges much faster than any other ecological or evolutionary process (1, 17). Understanding the potential and realized dispersal is thus key to ecology in general (18). When organisms’ spread occurs on the timescale of multiple generations, it is the byproduct of processes that take place at finer spatial and temporal scales that are the local movement and reproduction of individuals (5, 10). The main difficulty in causally understanding dispersal is thus to upscale processes that happen at the short-term individual level to long-term and broad-scale population patterns (5, 18–20). Furthermore, the large fluctuations observed in range expansions have been claimed to reflect an intrinsic lack of predictability of the phenomenon (21). Whether the variability observed in nature or in experimental ensembles might be accounted for by systematic differences between landscapes or by demographic stochasticity affecting basic vital rates of the organisms involved is an open research question (10, 18, 21, 22).Modeling of biological dispersal established the theoretical framework of reaction–diffusion processes (1–3, 23–25), which now finds common application in dispersal ecology (5, 14, 22, 26–30) and in other fields (17, 23, 25, 31–36). Reaction–diffusion models have also been applied to model human colonization processes (31), such as the Neolithic transition in Europe (25, 37, 38). The classical prediction of reaction–diffusion models (1, 2, 24, 25) is the propagation of an invading wavefront traveling undeformed at a constant speed (Fig. 1E). Such models have been widely adopted by ecologists to describe the spread of organisms in a variety of comparative studies (5, 10, 26) and to control the dynamics of invasive species (3, 4, 6). The extensive use of these models and the good fit to observational data favored their common endorsement as a paradigm for biological dispersal (6). However, current assessments (21) point at inherent limitations to the predictability of the phenomenon, due to its intrinsic stochasticity. Therefore, single realizations of a dispersal event (as those addressed in comparative studies) might deviate significantly from the mean of the process, making replicated experimentation necessary to allow hypothesis testing, identification of causal relationships, and to potentially falsify the models’ assumptions (39).Open in a separate windowFig. 1.Schematic representation of the experiment. (A) Linear landscape. (B) Individuals of the ciliate Tetrahymena sp. move and reproduce within the landscape. (C) Examples of reconstructed trajectories of individuals (Movie S1). (D) Individuals are introduced at one end of a linear landscape and are observed to reproduce and disperse within the landscape (not to scale). (E) Illustrative representation of density profiles along the landscape at subsequent times. A wavefront is argued to propagate undeformed at a constant speed v according to the Fisher–Kolmogorov equation.Here, we provide replicated and controlled experimental support to the theory of reaction–diffusion processes for modeling biological dispersal (23–25) in a generalized context that reproduces the observed fluctuations. Firstly, we experimentally substantiate the Fisher–Kolmogorov prediction (1, 2) on the existence and the mean speed of traveling wavefronts by measuring the individual components of the process. Secondly, we manipulate the inclusion of demographic stochasticity in the model to reproduce the observed variability in range expansions. We move from the Fisher–Kolmogorov equation (Materials and Methods) to describe the spread of organisms in a linear landscape (1, 2, 24, 25). The equation couples a logistic term describing the reproduction of individuals with growth rate r and carrying capacity K and a diffusion term accounting for local movement, epitomized by the diffusion coefficient D . These species’ traits define the characteristic scales of the dispersal process. In this framework, a population initially located at one end of a linear landscape is predicted to form a wavefront of colonization invading empty space at a constant speed (1, 2, 24, 25), which we measured in our dispersal experiment (Fig. 1D and SI Text).