There is accumulating neural evidence to support the existence of two distinct systems for guiding action selection, a deliberative "model-based" and a reflexive "model-free" system. However, little ...is known about how the brain determines which of these systems controls behavior at one moment in time. We provide evidence for an arbitration mechanism that allocates the degree of control over behavior by model-based and model-free systems as a function of the reliability of their respective predictions. We show that the inferior lateral prefrontal and frontopolar cortex encode both reliability signals and the output of a comparison between those signals, implicating these regions in the arbitration process. Moreover, connectivity between these regions and model-free valuation areas is negatively modulated by the degree of model-based control in the arbitrator, suggesting that arbitration may work through modulation of the model-free valuation system when the arbitrator deems that the model-based system should drive behavior.
All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a ...unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151–PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer.
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•PGT151 binds an interprotomer epitope formed by gp41 and gp120 on cleaved Env trimers•The PGT151 epitope does not overlap with any other epitope described so far•PGT151 enables isolation of functional cleaved Env from the cell membrane•Membrane-extracted and soluble SOSIP.664 Env trimers are structurally similar
This study sought to understand the nature of scientific globalism during a global crisis, particularly COVID-19. Findings show that scientific globalism occurs differently when comparing COVID-19 ...publications with non-COVID-19 publications during as well as before the pandemic. Despite the tense geopolitical climate, countries increased their proportion of international collaboration and open-access publications during the pandemic. However, not all countries engaged more globally. Countries that have been more impacted by the crisis and those with relatively lower GDPs tended to participate more in scientific globalism than their counterparts.
There is mounting concern that social media sites contribute to political polarization by creating “echo chambers” that insulate people from opposing views about current events. We surveyed a large ...sample of Democrats and Republicans who visit Twitter at least three times each week about a range of social policy issues. One week later, we randomly assigned respondents to a treatment condition in which they were offered financial incentives to follow a Twitter bot for 1 month that exposed them to messages from those with opposing political ideologies (e.g., elected officials, opinion leaders, media organizations, and nonprofit groups). Respondents were resurveyed at the end of the month to measure the effect of this treatment, and at regular intervals throughout the study period to monitor treatment compliance. We find that Republicans who followed a liberal Twitter bot became substantially more conservative posttreatment. Democrats exhibited slight increases in liberal attitudes after following a conservative Twitter bot, although these effects are not statistically significant. Notwithstanding important limitations of our study, these findings have significant implications for the interdisciplinary literature on political polarization and the emerging field of computational social science.
•Use bibliometric and survey data to analyze the dynamics of size, knowledge variety, and creativity in scientific teams.•Team size has inverted-U relation with novelty and continually increasing ...relation with impact.•Size–novelty relationship is driven by effect of knowledge variety.•Knowledge variety does not have a direct effect on impact, net of novelty and size.•Suggests the need for a governance approach to scientific work and S&T policies unpacking novelty and impact.
The increasing dominance of team science highlights the importance of understanding the effects of team composition on the creativity of research results. In this paper, we analyze the effect of team size, and field and task variety on creativity. Furthermore, we unpack two facets of creativity in science: novelty and impact. We find that increasing team size has an inverted-U shaped relation with novelty. We also find that the size–novelty relationship is largely due to the relation between size and team field or task variety, consistent with the information processing perspective. On the other hand, team size has a continually increasing relation with the likelihood of a high-impact paper. Furthermore, variety does not have a direct effect on impact, net of novelty. This study develops our understanding of team science and highlights the need for a governance approach to scientific work. We also advance the creativity literature by providing an ex ante objective bibliometric measure that distinguishes novelty from impact, and illustrate the distinct team-level drivers of each. We conclude with a discussion of the policy implications of our findings.
Recently measurements on various spin-1/2 quantum magnets such as H
LiIr
O
, LiZn
Mo
O
, ZnCu
(OH)
Cl
and 1T-TaS
-all described by magnetic frustration and quenched disorder but with no other common ...relation-nevertheless showed apparently universal scaling features at low temperature. In particular the heat capacity CH, T in temperature T and magnetic field H exhibits T/H data collapse reminiscent of scaling near a critical point. Here we propose a theory for this scaling collapse based on an emergent random-singlet regime extended to include spin-orbit coupling and antisymmetric Dzyaloshinskii-Moriya (DM) interactions. We derive the scaling CH, T/T ~ H
F
T/H with F
x = x
at small x, with q ∈ {0, 1, 2} an integer exponent whose value depends on spatial symmetries. The agreement with experiments indicates that a fraction of spins form random valence bonds and that these are surrounded by a quantum paramagnetic phase. We also discuss distinct scaling for magnetization with a q-dependent subdominant term enforced by Maxwell's relations.
It has previously been shown that the relative reliability of model-based and model-free reinforcement-learning (RL) systems plays a role in the allocation of behavioral control between them. ...However, the role of task complexity in the arbitration between these two strategies remains largely unknown. Here, using a combination of novel task design, computational modelling, and model-based fMRI analysis, we examined the role of task complexity alongside state-space uncertainty in the arbitration process. Participants tended to increase model-based RL control in response to increasing task complexity. However, they resorted to model-free RL when both uncertainty and task complexity were high, suggesting that these two variables interact during the arbitration process. Computational fMRI revealed that task complexity interacts with neural representations of the reliability of the two systems in the inferior prefrontal cortex.
Recommendations (New Section)258 Aortic Stenosis259 Aortic Stenosis259 Choice of Intervention: Recommendations259 Mitral Regurgitation261 Stages of Chronic MR261 Chronic Primary MR262 Intervention: ...Recommendations262 Chronic Secondary MR264 Intervention: Recommendations264 Prosthetic Valves265 Evaluation and Selection of Prosthetic Valves265 Intervention: Recommendations265 Antithrombotic Therapy for Prosthetic Valves267 Diagnosis and Follow-Up267 Medical Therapy: Recommendations267 Bridging Therapy for Prosthetic Valves269 Diagnosis and Follow-Up269 Medical Therapy: Recommendations269 Acute Mechanical Prosthetic Valve Thrombosis270 Diagnosis and Follow-Up: Recommendation270 Intervention: Recommendation271 Prosthetic Valve Stenosis271 Intervention: Recommendation272 Prosthetic Valve Regurgitation273 Intervention: Recommendations273 Infective Endocarditis274 Infective Endocarditis274 Intervention: Recommendations274 References276 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)283 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)284 Appendix 3 Abbreviations289 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. Criteria for commissioning an ERC and formal systematic review include: a) the absence of a current authoritative systematic review, b) the feasibility of defining the benefit and risk in a time frame consistent with the writing of Vilacosta, Aorto-cavitary fistulous tract formation in infective endocarditis: clinical and echocardiographic features of 76 cases and risk factors for mortality, Eur Heart J, Vol. 26, 2005, 288-297 270 K.L. Chan, Early clinical course and long-term outcome of patients with infective endocarditis complicated by perivalvular abscess, CMAJ, Vol. 167, 2002, 19-24 271 F. Jault, I. Gandjbakhch, J.C. Chastre, Prosthetic valve endocarditis with ring abscesses. Surgical management and long-term results, J Thorac Cardiovasc Surg, Vol. 105,...
Retroviral overexpression of reprogramming factors (Oct4, Sox2, Klf4, c-Myc) generates induced pluripotent stem cells (iPSCs). However, the integration of foreign DNA could induce genomic ...dysregulation. Cell-permeant proteins (CPPs) could overcome this limitation. To date, this approach has proved exceedingly inefficient. We discovered a striking difference in the pattern of gene expression induced by viral versus CPP-based delivery of the reprogramming factors, suggesting that a signaling pathway required for efficient nuclear reprogramming was activated by the retroviral, but not CPP approach. In gain- and loss-of-function studies, we find that the toll-like receptor 3 (TLR3) pathway enables efficient induction of pluripotency by viral or mmRNA approaches. Stimulation of TLR3 causes rapid and global changes in the expression of epigenetic modifiers to enhance chromatin remodeling and nuclear reprogramming. Activation of inflammatory pathways are required for efficient nuclear reprogramming in the induction of pluripotency.
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▸ TLR3 knockdown reduces the efficiency and yield of human iPSC generation ▸ TLR3 activation enhances human iPSC generation by cell permeant peptides ▸ TLR3 activation enables epigenetic changes to promote an open chromatin state ▸ Innate immune activation enhances nuclear reprogramming and cell plasticity
Efficient reprogramming of somatic cells to pluripotency depends on the activation of innate immune pathways, which cause changes in the expression of epigenetic modifiers and promote chromatin remodeling.
Incremental learning, in which new knowledge is acquired gradually through trial and error, can be distinguished from one-shot learning, in which the brain learns rapidly from only a single pairing ...of a stimulus and a consequence. Very little is known about how the brain transitions between these two fundamentally different forms of learning. Here we test a computational hypothesis that uncertainty about the causal relationship between a stimulus and an outcome induces rapid changes in the rate of learning, which in turn mediates the transition between incremental and one-shot learning. By using a novel behavioral task in combination with functional magnetic resonance imaging (fMRI) data from human volunteers, we found evidence implicating the ventrolateral prefrontal cortex and hippocampus in this process. The hippocampus was selectively "switched" on when one-shot learning was predicted to occur, while the ventrolateral prefrontal cortex was found to encode uncertainty about the causal association, exhibiting increased coupling with the hippocampus for high-learning rates, suggesting this region may act as a "switch," turning on and off one-shot learning as required.
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