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The ring-shaped cohesin complex topologically entraps two DNA molecules to establish sister chromatid cohesion. Cohesin also shapes the interphase chromatin landscape with wide-ranging implications for gene regulation, and cohesin is thought to achieve this by actively extruding DNA loops without topologically entrapping DNA. The 'loop extrusion' hypothesis finds motivation from in vitro observations—whether this process underlies in vivo chromatin loop formation remains untested. Here, using the budding yeast S. cerevisiae, we generate cohesin variants that have lost their ability to extrude DNA loops but retain their ability to topologically entrap DNA. Analysis of these variants suggests that in vivo chromatin loops form independently of loop extrusion. Instead, we find that transcription promotes loop formation, and acts as an extrinsic motor that expands these loops and defines their ultimate positions. Our results necessitate a re-evaluation of the loop extrusion hypothesis. We propose that cohesin, akin to sister chromatid cohesion establishment at replication forks, forms chromatin loops by DNA–DNA capture at places of transcription, thus unifying cohesin's two roles in chromosome segregation and interphase genome organisation. Synopsis: The loop extrusion hypothesis has shaped current thinking about chromatin organization by SMC complexes. This article experimentally tests the hypothesis, with a negative outcome, and puts forward transcription as an alternative, external motor force promoting chromatin loop formation. Yeast cohesin variants unable to perform in vitro DNA loop extrusion readily form chromatin loops in vivo. Transcription occupies key roles in chromatin loop formation and growth. In a unified model, cohesin sequentially captures two DNAs to establish sister chromatid cohesion at DNA replication forks and chromatin loops at places of transcription. Cohesin variants defective in DNA loop extrusion in vitro can still form chromatin loops in living yeast cells. [ABSTRACT FROM AUTHOR]

The reaction of diphenylphosphine oxide successively with two aryne precursors was investigated in order to access valuable functionalizable nonsymmetrical dibenzophospholes. The reactions proved sensitive to substituents of aryne precursors able to coordinate the incoming lithiated nucleophile. [ABSTRACT FROM AUTHOR]

Chemical reactions generically require that particles come into contact. In practice, reaction is often imperfect and can necessitate multiple random encounters between reactants. In confined geometries, despite notable recent advances, there is to date no general analytical treatment of such imperfect transport-limited reaction kinetics. Here, we determine the kinetics of imperfect reactions in confining domains for any diffusive or anomalously diffusive Markovian transport process, and for different models of imperfect reactivity. We show that the full distribution of reaction times is obtained in the large confining volume limit from the knowledge of the mean reaction time only, which we determine explicitly. This distribution for imperfect reactions is found to be identical to that of perfect reactions upon an appropriate rescaling of parameters, which highlights the robustness of our results. Strikingly, this holds true even in the regime of low reactivity where the mean reaction time is independent of the transport process, and can lead to large fluctuations of the reaction time - even in simple reaction schemes. We illustrate our results for normal diffusion in domains of generic shape, and for anomalous diffusion in complex environments, where our predictions are confirmed by numerical simulations. Chemical reactions often require multiple random encounters between reactants, but a general, analytical treatment such imperfect transport-limited/influenced reactions in confined spaces has not yet been proposed. Here, the authors predict the full kinetics of these reactions for Markovian processes in large confining volumes. [ABSTRACT FROM AUTHOR]

Based on high‐resolution laboratory data of instantaneous surface elevation and fluid velocity associated with the propagation of short waves over a gently sloping beach (GLOBEX project), the present work compares two methods for predicting the wave setup. A one‐dimensional (cross‐shore) model is considered to solve the balance equation that links the pressure gradient induced by the mean surface elevation profile with the wave radiation stress (including wave roller) and bottom stress profiles. When compared to measurements and using a wave‐by‐wave approach, the mean elevation appears to be significantly better predicted with a nonlinear approach based on stream function theory than with the commonly used linear approach based on Airy wave theory. At the shoreline, the linear method overestimates the wave setup by at least about 50% while this error is globally reduced by a factor 2 to 4 in the nonlinear case. In the framework of this study, the combined contribution of bottom stress and wave roller to the wave setup appears secondary since it accounts for about 10% of the predicted setup at the shoreline. Alternative computational methods are also considered to model the wave setup. In the linear case, using a spectral instead of the wave‐by‐wave approach greatly improves the wave setup predictions. This improvement is related to the disparity between the representative wave height (and thus the wave energy) obtained from spectral and wave‐by‐wave analysis when short‐wave nonlinearity becomes significant. Plain Language Summary: The breaking of waves near the shore increases the mean sea level to a maximum at the shoreline. This so‐called wave setup is of fundamental importance in coastal dynamics, especially regarding flooding issues during storm events. Here, we use laboratory measurements of surface elevation and fluid velocity associated with waves propagating over a uniform beach to test the validity of wave setup predictions following two different approaches. The first one is based on the basic and common framework within which the waves are always represented by sinusoids, while the second one is based on a more elaborate and realistic representation of waves. We show that using the basic approach significantly overestimates the wave setup, while the more elaborate approach leads to more realistic predictions. Key Points: Laboratory data are used to assess the validity of wave setup predictions following linear and nonlinear approachesIn a wave‐by‐wave analysis wave setup predictions are greatly improved when accounting for short‐wave nonlinearityLinear wave setup predictions are improved using spectral instead of wave‐by‐wave approach due to a correct account of the wave energy [ABSTRACT FROM AUTHOR]

Owing to the high interest in the OCF3 group for pharmaceutical and agrochemical applications, trifluoromethoxylation received great attention in the last years with several new methods for this approach towards OCF3‐comprising compounds. Yet, it most often requires the beforehand preparation of specific F3CO− transfer reagents, which can be toxic, expensive, unstable, and/or generate undesired side‐products upon consumption. To circumvent this, the in‐situ generation of gaseous fluorophosgene from triphosgene, its conversion by fluoride into the OCF3 anion, and the direct use of the latter in nucleophilic substitutions is an appealing strategy, which, although recently approached, has not been fully exploited. We disclose herein our efforts towards this aim. [ABSTRACT FROM AUTHOR]

Semiflexible polymer rings whose bonds obey both angular and dihedral restrictions [M. Dolgushev and A. Blumen, J. Chem. Phys. 138, 204902 (2013)], are treated under exact closure constraints. This allows us to obtain semianalytic results for their dynamics, based on sets of Langevin equations. The dihedral restrictions clearly manifest themselves in the behavior of the mean-square monomer displacement. The determination of the equilibrium ring conformations shows that the dihedral constraints influence the ring curvature, leading to compact folded structures. The method for imposing such constraints in Gaussian systems is very general and it allows to account for heterogeneous (sitedependent) restrictions. We show it by considering rings in which one site differs from the others. [ABSTRACT FROM AUTHOR]

The synthesis of trifluoromethylthiolated ketenimines is herein described. They are easily synthesized from the corresponding α‐trifluoromethylthiolated oximes upon activation with triflic anhydride and a base. The presumed nitrilium ion resulting from the Beckmann rearrangement is deprotonated to lead to the key intermediate, whose stability brought by the fluorinated substituent was unforeseeable. The reaction of these new building blocks with a variety of nucleophiles affords a vast array of cyclic and acyclic products bearing the valuable SCF3 moiety. [ABSTRACT FROM AUTHOR]

This study presents unpublished field observations of infragravity waves, collected at the dissipative beach of Saint-Trojan (Oléron Island, France) during the storm Kurt (3 February 2017), characterized by incident short waves of significant heights reaching 9.5 m and peak periods reaching 22 s. Data analysis reveals the development of exceptionally large infragravity waves, with significant heights reaching 1.85 m close to shore. Field observations are complemented by numerical modeling with XBeach, which well reproduces the development of such infragravity waves. Model results reveal that infragravity waves were generated mainly through the bound wave mechanism, enhanced by the development of a phase lag with the shortwave energy envelope. Spectral analysis of the free surface elevation shows the generation of superharmonic and subharmonic infragravity waves, the latter dominating the free surface elevation variance close to shore. Modeling results suggest that subharmonic infragravity waves result, at least partly, from infragravity-wave merging, promoted by the combination of free and bound infragravity waves propagating across a several kilometer-wide surf zone. Due to the steeper slope of the upper part of the beach profile, observed and modeled reflection coefficients under moderate-energy show a strong tidal modulation, with a weak reflection at low tide (R² < 0.2) and a full reflection at high tide (R² ∼ 1.0). Under storm waves, the observed reflection coefficients remain unusually high for a dissipative beach (R2 ∼ 0.5 − 1.0), which is explained by the development of subharmonic infragravity waves with frequencies around 0.005 Hz, too long to suffer a substantial dissipation. [ABSTRACT FROM AUTHOR]

Bertin, X.; Mengual, B.; de Bakker, A.; Guérin, T.; Martins, K.; Pezerat, M., and Lavaud, L., 2020. Recent advances in tidal inlet morphodynamics modelling. In: Malvárez, G. and Navas, F. (eds.), Global Coastal Issues of 2020. Journal of Coastal Research, Special Issue No. 95, pp. 1016–1020. Coconut Creek (Florida), ISSN 0749-0208. Tidal inlets connect the ocean to inner water bodies and are present worldwide. Complex interactions between tides, waves and shallow bathymetry often drive fast morphological changes but the underlying processes remain only partly understood. To better understand these processes, the development and application of morphodynamic models represents a unique perspective. This paper evaluates the impact of recent developments in the modelling system SCHISM, which include: a WENO method to solve the Exner Equation, a 3D coupling between waves and currents using a vortex force formalism, an adaptive parameterization for the dissipation of short waves by breaking and improved representations for wave-induced sediment transport. In order to evaluate the relevance of these developments, SCHISM is applied to the Maumusson Inlet, a mixed-energy inlet located on the Western Coast of France. Model-data comparison reveals firstly that complex wave-current interactions take place over the inlet ebb-delta, that include partial wave blocking during the ebb. Compared to classical 2DH approaches, our improved modelling system better reproduces the dynamics of adjacent beaches, inlet migration under oblique waves and sediment infilling of the main channel under storm waves. The relevance of these developments is demonstrated at the mixed-energy Maumusson Inlet (France). [ABSTRACT FROM AUTHOR]

Objective: To assess appropriateness of end-of-life treatments provided to actively dying patients attending the emergency department of a primary care hospital. Methods: Retrospective cohort study of patients who died in the emergency department of a French primary care hospital between January 2014 and January 2017. The deceased were identified through the admissions register. Then, electronic medical records were screened for bio-demographic data, data relative to decisions to withhold or withdraw treatments, to diagnosis and to the care provided. Patients were clustered into two categories, actively dying or non-actively dying, using clinical opinion based on their medical records. Appropriateness of care was appraised following French guidelines. Results: One hundred and forty-six deaths were recorded. Actively dying patients mostly suffered from vascular conditions (29.4%). When compared to the overall sample, they were more likely to have decisions to withhold or withdraw treatments (OR=5.3 [1.56; 20.7], p-value=0.003), to have strong opioids (OR=5.32 [2.1; 13.9], p-value<0.0001), hypnotics (OR=2.6 [0.95; 8.39], p-value=0.05), and scopolamine (OR=2.5 [1.1; 6.13], p-value=0.03). Moreover, they were less likely to have unbeneficial treatments in terminal conditions, such as resuscitation care (OR=0.06 [0.001; 0.52], p=0.002) and antibiotics (OR=0.42 [0.19; 0.92], pvalue= 0.022). There were no differences in rate of hydration, venous access and use of tracheal aspirations. Conclusions: Overall, actively dying patients were appropriately supported. However, several issues regarding hydration management, drug administration routes, and broncho-pulmonary secretions management remain to be addressed. [ABSTRACT FROM AUTHOR]

Duplication and segregation of chromosomes involves dynamic reorganization of their internal structure by conserved architectural proteins, including the structural maintenance of chromosomes ( SMC) complexes cohesin and condensin. Despite active investigation of the roles of these factors, a genome-wide view of dynamic chromosome architecture at both small and large scale during cell division is still missing. Here, we report the first comprehensive 4D analysis of the higher-order organization of the Saccharomyces cerevisiae genome throughout the cell cycle and investigate the roles of SMC complexes in controlling structural transitions. During replication, cohesion establishment promotes numerous long-range intra-chromosomal contacts and correlates with the individualization of chromosomes, which culminates at metaphase. In anaphase, mitotic chromosomes are abruptly reorganized depending on mechanical forces exerted by the mitotic spindle. Formation of a condensin-dependent loop bridging the centromere cluster with the rDNA loci suggests that condensin-mediated forces may also directly facilitate segregation. This work therefore comprehensively recapitulates cell cycle-dependent chromosome dynamics in a unicellular eukaryote, but also unveils new features of chromosome structural reorganization during highly conserved stages of cell division. [ABSTRACT FROM AUTHOR]