Virtual social grooming in macaques and its psychophysiological effects.

Allogrooming is a widespread, pervasive activity among non-human primates. Besides its hygienic function, it is thought to be instrumental in maintaining social bonds and establishing hierarchical structures within groups. However, the question arises as to whether the physiological and social benefits derived from social touch stem directly from body stimulation, or whether other mechanisms come into play. We address this question by analyzing an elaborate social behavior that we observed in two adult male macaques. This behavior demonstrates the existence of a persistent motivation to interact through a form of simulated grooming, as the animals were housed in adjacent enclosures separated by a glass panel preventing direct tactile contact. We find that such virtual grooming produces similar physiological sensations and social effects as allogrooming. We suggest that this behavior engages affective and reward brain circuits to the same extent as real social touch, and that this is probably achieved through high level processes similar to those involved in bodily illusions or synaesthetic phenomena previously described in humans. This observation reveals the unsuspected capacity of non-human primates to invent alternative, quasi-symbolic strategies to obtain effects similar to those provided by direct bodily interaction, which are so important for maintaining social bonds.

Glycogen ß-particles surface characterized by a combination of size exclusion chromatography and pyrene excimer fluorescence before and after ß-amylolysis.

Size exclusion chromatography (SEC) and pyrene excimer formation (PEF) experiments were conducted to characterize the local density profile inside a glycogen sample before (Glycogen) and after (Gly-ß-LD) treatment with ß-amylase. These experiments were conducted to assess whether the density at the periphery of the glycogen particles was very high to limit access to proteins involved in the metabolism of glycogen as predicted by the Tier model or low as suggested by the Gilbert model. SEC analysis indicated that the density inside the Glycogen and Gly-ß-LD samples remained constant with particle size and was not affected by ß-amylolysis. Analysis of the PEF experiments conducted on the Glycogen and Gly-ß-LD samples labeled with 1-pyrenebutyric acid showed that the particles have a dense interior and loose corona. The conclusions reached by the SEC and PEF experiments agree with the Gilbert model and have implications for the association of glycogen ß-particles into larger α-particles.

Accurate Determination of the Average Rate Constant of Pyrene Excimer Formation for Pyrene-Labeled Macromolecules from the Analysis of Individual Fluorescence Decays with Sums of Exponentials.

The average rate constant (⟨k⟩) for pyrene excimer formation (PEF) between an excited and a ground-state pyrenyl label covalently attached to a pyrene-labeled macromolecule (PyLM) has been found to be an ideal parameter to probe macromolecular conformations due to its proportionality to the local concentration ([Py]loc) of pyrenyl labels in PyLM. To date, ⟨k⟩ has only been determined with the model-free analysis (MFA) involving the global analysis of the pyrene monomer and excimer fluorescence decays of PyLM. Unfortunately, the MFA is computationally demanding which prevents its widespread use. To circumvent this complication, a methodology is introduced that involves the analysis of individual fluorescence decays with sums of exponentials (SoE), which are commonly used in the analysis packages of commercial time-resolved fluorometers. The individual fluorescence decays of the pyrene monomer acquired with 286 PyLM were analyzed with a SoE to yield ⟨kSoE-M⟩. The strong correlation between ⟨kSoE-M⟩ and ⟨kMF⟩ obtained from the global MFA indicated that ⟨kSoE-M⟩ was a good representation of ⟨k⟩. Furthermore, the AE-/AE+ ratio, equal to the ratio of the sum of the negative pre-exponential factors over the sum of the positive pre-exponential factors, was determined by fitting the individual pyrene excimer fluorescence decays of the 286 PyLM with a SoE. AE-/AE+ was found to take a value between -1.0 and -0.8, indicating that the pyrenyl labels were not aggregated. This result indicated that [Py]loc was well described by ⟨kSoE-M⟩, so that ⟨kSoE-M⟩ could be used to describe the conformation of macromolecules in the same manner as ⟨kMF⟩. Consequently, the methodology based on the analysis of individual fluorescence decays with sums of exponentials to determine ⟨kSoE-M⟩ and AE-/AE+ provides a robust alternative to the use of the MFA for the study of PyLM to many scientists interested in the characterization of macromolecular conformations.

Location of a Hydrophobic Load in Poly(oligo(ethylene glycol) methyl ether methacrylate)s (PEGMAs) Dissolved in Water and Probed by Fluorescence.

Two series of pyrene-labeled poly(oligo(ethylene glycol) methyl ether methacrylate)s referred to as PyEG5-PEGnMA and PyC4-PEGnMA were prepared to probe the region surrounding the polymethacrylate backbone by using the fluorescence of the dye pyrene. PyEG5-PEGnMA and PyC4-PEGnMA were prepared by copolymerizing the EGnMA methacrylate monomers with penta(ethylene glycol) 1-pyrenemethyl ether methacrylate or 1-pyrenebutyl methacrylate, respectively. In organic solvents, the much longer 18 non-hydrogen atom linker connecting the pyrene moieties to the polymethacrylate backbone in the PyEG5-PEGnMA samples enabled the deployment of the pyrenyl labels into the solution. In water, however, an excited pyrene for PyEG5-PEGnMA was found to probe a same volume as for the PyC4-PEGnMA samples where a much shorter 6 non-hydrogen atom spacer connected pyrene to the backbone. Another surprising observation, considering that the hydrophobicity of pyrene induces strong pyrene aggregation for many pyrene-labeled water-soluble polymers (Py-WSPs) in water, was the little pyrene aggregation found for the PyEG5-PEGnMA and PyC4-PEGnMA samples in water. These effects could be related to the organic-like domain (OLD) generated by the oligo(ethylene glycol) side chains densely arranged around the polymethacrylate backbone of the polymeric bottlebrush (PBB). Additional fluorescence experiments conducted with the penta(ethylene glycol) 1-pyrenemethyl ether derivative indicated that the cylindrical OLD surrounding the polymethacrylate backbone had a chemical composition similar to that of ethylene glycol. Binding of hydrophobic pyrene molecules to unlabeled PEGnMA bottlebrushes in water further supported the existence of the OLD. The demonstration, that PEGnMA samples form an OLD in water, which can host and protect hydrophobic cargoes like pyrene, should lead to the development of improved PEGnMA-based drug delivery systems.

Distinct neural adaptations to time demand in the striatum and the hippocampus.

How do neural codes adjust to track time across a range of resolutions, from milliseconds to multi-seconds, as a function of the temporal frequency at which events occur? To address this question, we studied time-modulated cells in the striatum and the hippocampus, while macaques categorized three nested intervals within the sub-second or the supra-second range (up to 1, 2, 4, or 8 s), thereby modifying the temporal resolution needed to solve the task. Time-modulated cells carried more information for intervals with explicit timing demand, than for any other interval. The striatum, particularly the caudate, supported the most accurate temporal prediction throughout all time ranges. Strikingly, its temporal readout adjusted non-linearly to the time range, suggesting that the striatal resolution shifted from a precise millisecond to a coarse multi-second range as a function of demand. This is in line with monkey's behavioral latencies, which indicated that they tracked time until 2 s but employed a coarse categorization strategy for durations beyond. By contrast, the hippocampus discriminated only the beginning from the end of intervals, regardless of the range. We propose that the hippocampus may provide an overall poor signal marking an event's beginning, whereas the striatum optimizes neural resources to process time throughout an interval adapting to the ongoing timing necessity.

Appraisal of blob-Based Approaches in the Prediction of Protein Folding Times.

A series of reports published in the last 3 years has illustrated that a blob-based model (BBM) can predict the folding time of proteins from their primary amino acid (aa) sequence based on three simple rules established to characterize the long-range backbone dynamics (LRBD) of racemic polypeptides. The sole use of LRBD to predict protein folding times with the BBM represents a radical departure from all other prediction methods currently applied to determine protein folding times, which rely instead on parameters such as the structure content, folding kinetics, chain length, amino acid properties, or contact topography of proteins. Furthermore, the built-in modularity of the BBM enables the parametrization and inclusion of new phenomena affecting the LRBD of polypeptides, while its conceptual simplicity makes it an interesting new mathematical tool for studying protein folding. However, its novelty implies that its relationship with many other methods used to predict protein folding times has not been well researched. Consequently, the purpose of this report is to uncover the physical phenomena encountered during protein folding that are best described by the BBM through the identification of parameters that have been recognized over the years as being strong predictors for protein folding, such as protein size, topology, structural class, and folding kinetics. This was accomplished by determining the parameters most strongly correlated with the folding times predicted by the BBM. While the BBM in its present form appears to be a good indicator of the folding times of the vast majority of the 195 proteins considered so far, this report finds that it excels for moderately large proteins that are primarily composed of locally formed structural motifs such as α-helices or for proteins that fold in multiple steps. Altogether, these observations based on the use of the BBM support the notion that proteins fold the way they do because the LRBD of polypeptides is mostly driven by the local interactions experienced between aa's within reach of one another.

Persistence Length of PEGMA Bottle Brushes Determined by Pyrene Excimer Fluorescence.

Seven pyrene-labeled poly(oligo(ethylene glycol) methyl ether methacrylate)s (PyEG5-PEGnMAs) were prepared with n = 0, 3, 4, 5, 7, 9, and 19 ethylene glycol units by copolymerizing a small amount of penta(ethylene glycol) 1-pyrenemethyl ether methacrylate with an EGnMA monomer. The conformation of the PyEG5-PEGnMA polymers evolved from a random coil for PyEG5-PEG0MA or poly(methyl methacrylate) to a polymeric bottle brush (PBB) architecture with increasing side chain length. The fluorescence decays of the PyEG5-PEGnMA samples were fitted according to the fluorescence blob model (FBM) whose parameters were used, in combination with the Kratky-Porod equation, to calculate the persistence length of these polymers. The persistence lengths obtained from the PEF experiments were found to increase with the square of the number (NS) of non-hydrogen atoms in the side chain as expected theoretically. The persistence lengths found with the PyEG5-PEGnMA samples in DMF also matched those found earlier for another series of PEGnMA samples labeled with 1-pyrenebutanol. The good agreement found between the persistence lengths obtained with the PEGnMA samples labeled with two different pyrene derivatives illustrates the robustness of the method and its applicability for measuring the unknown persistence length of polydisperse polymer samples.

Intramacromolecular Conformational Changes in Low Generation PAMAM Dendrimers Probed by Pyrene Excimer Formation.

Pyrene excimer formation (PEF) was used to probe the intramacromolecular conformational change experienced by low generation pyrene-labeled PAMAM dendrimers referred to as PyCX-PAMAM-GY, where X (=4, 8, or 12) and Y (=0, 1, or 2) represent the number of atoms in the pyrenyl linker and the dendrimer generation, respectively. Each sample was studied in N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) with and without 5 mM HCl. Global analysis of the monomer and excimer time-resolved fluorescence decays using the model free analysis (MFA) yielded the average rate constant of excimer formation, ⟨k⟩, which was compared with the local pyrene concentration ([Py]loc) of the PyCX-PAMAM-GY samples calculated by assuming that the oligomeric segments constituting the dendrimer's interior obeyed Gaussian statistics. A notable decrease in ⟨k⟩ was observed upon the addition of 5 mM HCl to the PyCX-PAMAM-GY solutions and was attributed to swelling of the dendrimers resulting from the protonation of the internal tertiary amines. The reversibility of this conformational change could also be monitored via PEF. Solvent differences between DMF and DMSO were accounted for by dividing ⟨k⟩ by kdiff, the bimolecular rate constant for diffusive PEF of a n-hexyl-1-pyrenebutyramide model compound, to yield the ⟨k⟩/kdiff ratio. Comparison between the ⟨k⟩/kdiff ratios obtained for all the PyCX-PAMAM-GY samples with and without 5 mM HCl revealed a 13% increase in the radius of the PAMAM-GY dendrimers upon protonation of their internal tertiary amines in agreement with earlier reports. These experiments illustrate that PEF represents a powerful experimental means to quantitatively probe the intramacromolecular conformational changes of complex macromolecules in solution, in a manner that complements scattering techniques.

Probing the inner local density of complex macromolecules by pyrene excimer formation.

The direct relationship existing between the average rate constant 〈k〉 for pyrene excimer formation and the local concentration [Py]loc of ground-state pyrenyl labels covalently attached to a macromolecule was established for 55 pyrene-labeled macromolecules (PyLM). These PyLM belonged to three different families of macromolecules with the first representing short monodisperse linear chains end-labeled with pyrene (polystyrene, poly(ethylene oxide), and poly(N-isopropyl acrylamide)), the second representing long polydisperse linear chains randomly labeled with pyrene (poly(methyl acrylate), poly(methyl methacrylate), polystyrene, poly(butyl methacrylate), poly(methoxyethyl methacrylate), and poly(N-isopropyl acrylamide)), and the third being comprised of two series of pyrene end-labeled low generation dendrimers with a bis(hydroxymethyl)propionic acid or a polyamidoamine backbone. The assumption, that the polymeric segments probed by an excited pyrenyl label covalently attached to one of these macromolecules obeyed Gaussian statistics, enabled the calculation of their square root average squared end-to-end distance (LPy), which was applied to calculate [Py]loc. The log-log plots of 〈k〉 as a function of [Py]loc yielded straight lines with a slope of unity for all families of macromolecules studied in four different organic solvents demonstrating the validity and generality of the 〈k〉-vs.-[Py]loc relationship. Since an experimentalist knows how the the pyrenyl labels are covalently attached onto a macromolecule, [Py]loc offers a means to probe the local density of a macromolecule, which can be employed to characterize its conformation in solution. Consequently, the 〈k〉-vs.-[Py]loc relationship provides a novel experimental means to probe the conformation of macromolecules which should establish pyrene excimer formation as an appealing method for conformational studies of macromolecules in solution, which should nicely complement scattering techniques.

Synthesis and Characterization of Furan-Based Non-Ionic Surfactants (fbnios).

Two series of furan-based non-ionic surfactants (fbnios) were prepared by a combination of Williamson ether synthesis and anionic polymerization of ethylene oxide (EO). The reaction of 1-bromooctane and 1-bromododecane with 2,5-bis(hydroxymethyl)furan after deprotonation with potassium tert-butoxide yielded the corresponding alkane furfuryl alcohols (Cx-F-OH with x = 8 or 12). Deprotonation of Cx-F-OH with potassium tert-pentoxide enabled the anionic polymerization of EO, which yielded four C8-F-EOy samples with y = 3, 6, 9, and 14 and four C12-F-EOy samples with y = 9, 12, 18, and 23. The chemical composition of the fbnios was determined by NMR and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS) analysis, while their dispersity (D) was characterized by gel permeation chromatography (GPC) and MALDI-ToF MS. The purity of the Cx-F-EOy samples exceeded 92%, and they were produced with narrow molecular weight distributions (D ≤ 1.02, as determined by GPC analysis). The critical micelle concentration (CMC) of the Cx-F-EOy samples was determined by surface tension and pyrene fluorescence measurements. These showed that the CMC of the fbnios could be tuned by adjusting the molecular parameters x and y, with the CMC increasing for decreasing x and increasing y. In particular, the CMC of the C8-F-EOy and C12-F-EOy samples was significantly higher and lower, respectively, than for typical non-ionic surfactants (nios) like the Triton X and Brij surfactant families. The efficiency, effectiveness, and cross section of the EOy headgroup of the fbnios were also determined. Together, the CMC, efficiency, and effectiveness of the fbnios demonstrate that this new surfactant family displays tensioactive properties that match and even exceed those of traditional nios, suggesting that they could extend further the already broad range of applications for nios.

Characterization of Polyisobutylene Succinic Anhydride (PIBSA) and Its PIBSI Products from the Reaction of PIBSA with Hexamethylene Diamine.

The nature of the end-groups of a PIBSA sample, namely a polyisobutylene (PIB) sample, where each chain is supposedly terminated at one end with a single succinic anhydride group, was characterized through a combination of pyrene excimer fluorescence (PEF), gel permeation chromatography, and simulations. The PIBSA sample was reacted with different molar ratios of hexamethylene diamine to generate PIBSI molecules with succinimide (SI) groups in the corresponding reaction mixtures. The molecular weight distribution (MWD) of the different reaction mixtures was determined by fitting the gel permeation chromatography traces with sums of Gaussians. Comparison of the experimental MWD of the reaction mixtures with those simulated by assuming that the reaction between succinic anhydride and amine occurs through stochastic encounters led to the conclusion that 36 wt% of the PIBSA sample constituted unmaleated PIB chains. Based on this analysis, the PIBSA sample was found to be constituted of 0.50, 0.38, and 0.12 molar fractions of PIB chains that were singly maleated, unmaleated, and doubly maleated, respectively.

Coaxial assembly of helical aromatic foldamers by metal coordination.

Deprotonation of acid-terminated helical aromatic foldamers with a mineral base in chlorinated solvents led to their dimerization through the coordination of a metal cation (Li+, Na+, K+, Ag+, or Hg2+) with the terminal carboxylate functions. This new ligation method was applied to oligomerize diacid-functionalized foldamers.

Interior of glycogen probed by pyrene excimer fluorescence.

A glycogen sample from oyster (O) and another from corn (C) were fluorescently labeled with 1-pyrenebutyric acid to yield two series of pyrene-labeled glycogen samples (Py-Glycogen(O/C)). Analysis of the time-resolved fluorescence (TRF) measurements of the Py-Glycogen(O/C) dispersions in dimethyl sulfoxide yielded the maximum number () of anhydroglucose units (AGUs), that could separate two pyrene-labeled AGUs and still allow efficient pyrene excimer formation (PEF) between an excited and a ground-state pyrene. Molecular mechanics optimizations (MMOs) were conducted on a lattice of hexagonally close packed oligosaccharide helices to determine how the theoretical Nblobtheo varied as a function of the lattice density. Comparing and , obtained after integrating Nblobtheo along the local density profile ρ(r) across the glycogen particles, led to the conclusion that ρ(r) took a maximum value at the center of the glycogen particles contrary to expectations based on the Tier Model.

Synergetic Effects of Alanine and Glycine in Blob-Based Methods for Predicting Protein Folding Times.

The polypeptide PGlyAlaGlu was prepared with 20 mol % glycine (Gly), 36 mol % d,l-alanine (Ala), and 44 mol % d,l-glutamic acid (Glu) and labeled with the dye 1-pyrenemethylamine to yield a series of Py-PGlyAlaGlu samples. The fluorescence decays of the Py-PGlyAlaGlu samples were analyzed according to the fluorescence blob model (FBM) to obtain the number Nblobexp of amino acids (aa's) encompassed inside the subvolume Vblob of the polypeptide probed by an excited pyrene. An Nblobexp value of 29 (±2) was retrieved for Py-PGlyAlaGlu, which was much larger than for any of the copolypeptide PGlyGlu or PAlaGlu prepared with either Gly and Glu or Ala and Glu, respectively. The continuous increase in Nblobexp with decreasing side chain size (SCS) from 10 aa's for PGlu to 16 aa's for PAlaGlu and 22 aa's for PGlyGlu was used earlier to define the reach of an aa and determine the groups of aa's that could interact with each other along a polypeptide backbone according to their SCS. These groups of aa's, referred to as blobs, led to the implementation of blob-based models (BBM) to predict the folding time τFtheo,BBM of 145 proteins, which was found to match their experimental folding time τFexp with a relatively high 0.71 correlation coefficient. Nevertheless, the much higher Nblobexp value found for Py-PGlyAlaGlu compared to all other pyrene-labeled polypeptides studied to date indicates that the reach of aa's along a polypeptide sequence is affected not only by SCS but also by synergetic effects between different aa's. Following this new insight, a revised BBM was implemented to predict τFtheo,BBM for 195 proteins assuming the existence or absence of synergies to control the interactions between aa's along a polypeptide sequence. Similarly good correlation coefficients of 0.71 and 0.74 were obtained for a direct 1:1 comparison of τFexp and τFtheo,BBM for the 195 proteins without and with synergies, respectively. This result suggests that synergetic effects between different aa's have little effect on τFtheo,BBM predicted from BBM underlying the robustness of this methodology.

Assessing the allocation of attention during visual search using digit-tracking, a calibration-free alternative to eye tracking.

Digit-tracking, a simple, calibration-free technique, has proven to be a good alternative to eye tracking in vision science. Participants view stimuli superimposed by Gaussian blur on a touchscreen interface and slide a finger across the display to locally sharpen an area the size of the foveal region just at the finger's position. Finger movements are recorded as an indicator of eye movements and attentional focus. Because of its simplicity and portability, this system has many potential applications in basic and applied research. Here we used digit-tracking to investigate visual search and replicated several known effects observed using different types of search arrays. Exploration patterns measured with digit-tracking during visual search of natural scenes were comparable to those previously reported for eye-tracking and constrained by similar saliency. Therefore, our results provide further evidence for the validity and relevance of digit-tracking for basic and applied research on vision and attention.

Cluster Size of Amylopectin and Nanosized Amylopectin Fragments Characterized by Pyrene Excimer Formation.

Amylopectin from waxy corn and the three nanosized amylopectin fragments (NAFs)-NAF(56), NAF(20), and NAF(8)-from waxy corn starch with a hydrodynamic diameter of 227, 56, 20, and 8 nm, respectively, were randomly labeled with 1-pyrenebutyric acid. The efficiency of these pyrene-labeled amylopectin-based polysaccharides (Py-AbPS) for pyrene excimer formation (PEF) upon diffusive encounter between an excited and a ground-state pyrene increased with increasing concentration of unlabeled NAF(56) in Py-AbPS dispersions in DMSO. Fluorescence decay analysis of the Py-AbPS dispersions in DMSO prepared with increasing [NAF(56)] yielded the maximum number (Nblobexp) of anhydroglucose units (AGUs) separating two pyrene-labeled AGUs while still allowing PEF. Comparison of Nblobexp with Nblobtheo, obtained by conducting molecular mechanics optimizations on helical oligosaccharide constructs with HyperChem, led to a relationship between the interhelical distance (dh-h) in a cluster of oligosaccharide helices, [NAF(56)], and the number of helices in a cluster. It was found that the AbPSs were composed of building blocks made of 3.5 (±0.9) helices that self-assembled into increasingly larger clusters with increasing [NAF(56)]. The ability of PEF-based experiments to yield the cluster size of AbPSs provides a new experimental means to probe the interior of AbPSs at the molecular level.

Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC. METHODS: In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling. FINDINGS: Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported. INTERPRETATION: The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures. FUNDING: French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Characterization of the Interactions between an Unassociated Cationic Pyrene-Labeled Gemini Surfactant and Anionic Sodium Dodecyl Sulfate.

The gemini surfactant PyO-3-12, made of two dimethylammonium bromides joined by a propyl linker and bearing a dodecyl pendant on one side and a 1-pyrenemethoxyhexyl group on the other side, was employed to probe the interactions between positively charged PyO-3-12 and negatively charged sodium dodecyl sulfate (SDS). PyO-3-12 was selected for its ability to respond to the polarity of its local environment through the fluorescence intensity ratio I1/I3 of the first-to-third fluorescence peaks of the pyrene monomer and the local pyrene concentration [Py]loc through the IE/IM ratio of the pyrene excimer-to-pyrene monomer fluorescence intensity. Furthermore, analysis of the fluorescence decays of aqueous solutions of PyO-3-12 and SDS yielded a measure of the internal dynamics, local concentration, and state (associated vs unassociated) of PyO-3-12 in solution. By following these parameters for aqueous solutions prepared with a constant PyO-3-12 concentration of either 1, 4, or 16 µM and SDS concentrations ranging from 0 to 200 mM, six SDS concentration regimes were identified to describe the interactions between PyO-3-12 and SDS in pure water. Sharp transitions of the parameters describing the fluorescence of pyrene marked the boundaries between the different regimes. Perhaps the most important transition was the one defining the formation of the PyO-3-12/SDS aggregates, which was completed at the equicharge point, implying that they were constituted of 1 meq of PyO-3-12 and 2 meq of SDS. The low I1/I3 ratio obtained for the PyO-3-12/SDS aggregates suggested that they were multilamellar aggregates, which would shield the pyrenyl labels from polar water. The formation of these multilamellar aggregates was confirmed by transmission electron microscopy (TEM), which demonstrated the existence of multilamellar vesicles, whose presence increased with decreasing PyO-3-12 concentration. This study suggests that the combination of pyrene excimer formation and TEM provides an interesting experimental means to probe the assemblies generated from oppositely charged surfactants at surfactant concentrations, which are much lower than their critical micelle concentration.

Pyrene Excimer Formation (PEF) and Its Application to the Study of Polypeptide Dynamics.

This Perspective describes how the fluorescence blob model (FBM) has been developed and applied over the past 30 years to characterize the long-range backbone dynamics (LRBD) of polymers in solution. In these experiments, the polymers are randomly labeled with the dye pyrene, which forms an excimer upon the encounter between an excited and a ground-state pyrenyl label inside a finite subvolume of the polymer coil referred to as a blob representing the volume probed by the excited pyrene. By compartmentalizing the polymer coil into a cluster of identical blobs, FBM analysis of the fluorescence decays acquired with the polymers yields the number Nblob of structural units inside a blob. Since a flexible or rigid backbone will result in an Nblob that is either large or small, Nblob can be used as a measure of the flexibility of a given polymer. After having established that these experiments based on pyrene excimer formation (PEF) yielded quantitative information about the LRBD of a variety of polymers in solution, control experiments were carried out to characterize the effects that different molecular variables, such as the side-chain size (SCS) of a structural unit or the length of the linker connecting pyrene to the polymeric backbone, had on the parameters retrieved with the FBM. At this point, the FBM was applied to study the LRBD of polypeptides prepared from racemic mixtures of amino acids (aa's). These studies led to the establishment of simple rules that could be developed into mathematical equations to describe the LRBD of polypeptides. The Nblob values retrieved from the FBM analysis of the fluorescence decays acquired with the pyrene-labeled polypeptides could then be employed to predict the total conformational search time (τtcs) of any polypeptide based on their sequence. Strong correlations were found between the predicted τtcs and the experimental folding times of 145 proteins. The good quality of these correlations suggests that the blob-based approach described in this report might represent an interesting mathematical means for studying protein folding.

Culture-free perceptual invariant for trustworthiness.

Humans beings decide to trust others selectively, often based on the appearance of a face. But how do observers deal with the wide variety of facial morphologies and, in particular, those outside their own familiar cultural group? Using reverse correlation, a data-driven approach to explore how individuals create internal representations without external biases, we studied the generation of trustworthy faces by French and Chinese participants (N = 160) within and outside their own cultural group. Participants selected the most trustworthy or attractive (control condition) face from two identical European or Asian descent faces that had been modified by different noise masks. A conjunction analysis to reveal facial features common to both cultures showed that Chinese and French participants unconsciously increased the contrast of the "pupil-iris area" to make the face appear more trustworthy. No significant effects common to both groups were found for the attraction condition suggesting that attraction judgements are dependent on cultural processes. These results suggest the presence of universal cross-cultural mechanisms for the construction of implicit first impressions of trust, and highlight the importance of the eyes area in this process.