Best friends: children use mutual gaze to identify friendships in others

This study examined children’s ability to use mutual eye gaze as a cue to friendships in others. In Experiment 1, following a discussion about friendship, 4-, 5-, and 6-year-olds were shown animations in which three cartoon children looked at one another, and were told that one target character had a best friend. Although all age groups accurately detected the mutual gaze between the target and another character, only 5- and 6-year-olds used this cue to infer friendship. Experiment 2 replicated the effect with 5- and 6-year-olds when the target character was not explicitly identified. Finally, in Experiment 3, where the attribution of friendship could only be based on synchronized mutual gaze, 6-year-olds made this attribution, while 4- and 5-year-olds did not. Children occasionally referred to mutual eye gaze when asked to justify their responses in Experiments 2 and 3, but it was only by the age of 6 that reference to these cues correlated with the use of mutual gaze in judgements of affiliation. Although younger children detected mutual gaze, it was not until 6 years of age that children reliably detected and justified mutual gaze as a cue to friendship

Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains but also enables us to derive analytic expressions for key properties such as the dynamic range and $[EC_{50}]$. Finally, we derive an expression for the free energy of allosteric repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.Comment: Substantial revisions for resubmission (3 new figures, significantly elaborated discussion); added Professor Mitchell Lewis as another author for his continuing contributions to the projec

Teaching Wikipedia: A Model for Critical Engagement with Open Information

In this chapter, the authors describe the learning experience and goals of a class assignment to write content for Wikipedia about women in science and technology fields. The authors, a university professor and two librarians, collaboratively developed this assignment to allow students to engage in rigorous research and contribute to the visibility of women scientists by writing content for the web. The authors chose the Wikipedia platform as the means to make the students work openly available because of its ubiquity and the potential for student work to make an important impact. The assignment, used in two iterations of the course, was designed to provide students not only with a hands-on experience on working on the open web, but also with tools to assess critically the uses and abuses of open access platforms

The Energetics of Molecular Adaptation in Transcriptional Regulation

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of Escherichia coli, probing several mutations in the DNA binding and inducer binding domains. We find that the change in gene expression due to a point mutation can be captured by modifying only a subset of the model parameters that describe the respective domain of the wild-type protein. These parameters appear to be insulated, with mutations in the DNA binding domain altering only the DNA affinity and those in the inducer binding domain altering only the allosteric parameters. Changing these subsets of parameters tunes the free energy of the system in a way that is concordant with theoretical expectations. Finally, we show that the induction profiles and resulting free energies associated with pairwise double mutants can be predicted with quantitative accuracy given knowledge of the single mutants, providing an avenue for identifying and quantifying epistatic interactions.Comment: 11 pages, 6 figures, supplemental info. available via http://rpgroup.caltech.edu/mwc_mutant

Géomatériaux imprimables en 3D

International audienceOne of the many attributes of 3D printing is the ability to produce particles with independent control of morphology and material properties, parameters that are inexorably entwined in naturally occurring geomaterials. In this paper we describe the 3D printing of surrogate granular materials, show examples of the particles produced and present results showing their ability to capture real soil behaviour. Three approaches are demonstrated for the three dimensional generation of model grains. The first method involves the superimposition of a fractal surface with higher level stochastic features on the face of a closed volume such as a geodesic spheroid. The second method involves the use of Fourier descriptors or fractal geometry generated from 2D cross sections and their interpolation to produce simulated geomaterial particles in three dimensions. The third method involves the generation of complex particles by the aggregation of polyhedral elements such as cubes or octahedra which is suitable for the simulation and fabrication of porous or branching particles. Finally, we discuss applications of the fabrication of surrogate materials by 3D printing for use as standardised, printable geomaterials in future up-scaled geotechnical experiments and other geomechanical research.https://doi.org/10.1680/jgeot.15.P.034L'un des nombreux attributs de l'impression 3D est la capacité de produire des particules avec un contrôle indépendant de la morphologie et des propriétés du matériau, paramètres inextricablement liés dans les géomatériaux naturels. Dans cet article, nous décrivons l'impression 3D de matériaux granulaires de substitution, montrons des exemples de particules produites et présentons les résultats montrant leur capacité à capturer le comportement réel du sol. Trois approches sont démontrées pour la génération tridimensionnelle de grains modèles. La première méthode implique la superposition d'une surface fractale avec des caractéristiques stochastiques de niveau supérieur sur la face d'un volume fermé tel qu'un sphéroïde géodésique. La deuxième méthode implique l'utilisation de descripteurs de Fourier ou de géométrie fractale générés à partir de sections transversales 2D et leur interpolation pour produire des particules de géomatériau simulées en trois dimensions. La troisième méthode implique la génération de particules complexes par l'agrégation d'éléments polyédriques, tels que des cubes ou des octaèdres, qui conviennent à la simulation et à la fabrication de particules poreuses ou ramifiées. Enfin, nous discutons des applications de la fabrication de matériaux de substitution par impression 3D pour une utilisation en tant que géomatériaux imprimables et normalisés dans de futures expériences géotechniques à grande échelle et autres recherches géomécaniques.https://doi.org/10.1680/jgeot.15.P.03

Procalcitonin levels in candidemia versus bacteremia: A systematic review

open7BackgroundProcalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in thein the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia.MethodsPubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia.ResultsWe included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-d-glucan) but more data is needed.ConclusionsPCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence.openCortegiani A.; Misseri G.; Ippolito M.; Bassetti M.; Giarratano A.; Martin-Loeches I.; Einav S.Cortegiani, A.; Misseri, G.; Ippolito, M.; Bassetti, M.; Giarratano, A.; Martin-Loeches, I.; Einav, S

Procalcitonin levels in candidemia versus bacteremia: A systematic review

Background: Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia. Methods: PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia. Results: We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-D-glucan) but more data is needed. Conclusions: PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence

Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review

Background: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. Methods: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. Results: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. Conclusions: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight

The association between implicit and explicit affective inhibitory control, rumination and depressive symptoms

Inhibitory control underlies one’s ability to maintain goal-directed behavior by inhibiting prepotent responses or ignoring irrelevant information. Recent models suggest that impaired inhibition of negative information may contribute to depressive symptoms, and that this association is mediated by rumination. However, the exact nature of this association, particularly in non-clinical samples, is unclear. The current study assessed the relationship between inhibitory control over emotional vs. non-emotional information, rumination and depressive symptoms. A non-clinical sample of 119 participants (mean age: 36.44 ± 11.74) with various levels of depressive symptoms completed three variations of a Go/No-Go task online; two of the task variations required either explicit or implicit processing of emotional expressions, and a third variation contained no emotional expressions (i.e., neutral condition). We found reductions in inhibitory control for participants reporting elevated symptoms of depression on all three task variations, relative to less depressed participants. However, for the task variation that required implicit emotion processing, depressive symptoms were associated with inhibitory deficits for sad and neutral, but not for happy expressions. An exploratory analysis showed that the relationship between inhibition and depressive symptoms occurs in part through trait rumination for all three tasks, regardless of emotional content. Collectively, these results indicate that elevated depressive symptoms are associated with both a general inhibitory control deficit, as well as affective interference from negative emotions, with implications for the assessment and treatment of mood disorders