Outstanding performance of PIM-1 membranes towards the separation of fluorinated refrigerant gases

The recycling of depleted high global warming mixtures of fluorinated gases (F-gases) with close-boiling or azeotropic behavior requires advanced separation processes to obtain effectively the pure components. Herein, several types of PIM-1 membranes were tested for the first time towards the separation of hydrofluorocarbons and hydrofluoroolefins, showing extraordinarily high permeability coefficients for the value-added difluoromethane (R-32), up to 4100 barrer, coupled with high selectivity for the F-gas pairs of interest. Additionally, the solubility of selected F-gases in PIM-1 was measured and fitted to the dual-mode and Guggenheim, Anderson and de Boer sorption models. The separation performance of the standard PIM-1 and a highly branched PIM-1 was examined with the mixture R-410A (containing R-32 and pentafluoroethane R-125) to assess the influence of the membrane topology on the mixed-gas permeation properties over time (physical aging). Considering that the branched PIM-1 membrane was the least impacted by the aging phenomena, it was used to recover high purity R-32 (concentration in the permeate side as high as 98.9 vol % was achieved) from refrigerant gas mixtures R-410A and R-454B (mixture of R-32 and R-1234yf) in continuous long-term experiments. Results showed the great potential of PIM-1 membranes for the separation of R-32 from refrigerant mixtures collected from end-of-life equipment.This research is supported by project PID2019-105827RB-I00 funded by MCIN/AEI/10.13039/501100011033. F.P. and S.V.G.H. acknowledge the support of the Spanish State Research Agency and the Spanish Ministry of Science and Innovation (grants IJC2020-043134-I and PRE2020-093568, respectively). A.B.F and P.M.B acknowledge EPSRC Grant ep/v047078/1 (SynHiSel). P.G. is supported by Grant RYC2019-027060-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”

Kinetic analysis of the early signaling steps of the human chemokine receptor CXCR4

G protein-coupled receptors (GPCRs) are biological switches that transduce extracellular stimuli into intracellular responses in the cell. Temporally resolving GPCR transduction pathways is key to understanding how cell signaling occurs. Here, we investigate the kinetics and dynamics of the activation and early signaling steps of the chemokine receptor CXCR4 in response to its natural ligands CXCL12 and macrophage migration inhibitory factor (MIF), using Förster resonance energy transfer-based approaches. We show that CXCR4 presents a multifaceted response to CXCL12, with receptor activation (≈0.6s) followed by a rearrangement in the receptor/G protein complex (≈1s), a slower dimer rearrangement (≈1.7s) and prolonged G protein activation (≈4s). In comparison, MIF distinctly modulates every step of the transduction pathway, indicating distinct activation mechanisms and reflecting the different pharmacological properties of these two ligands. Our study also indicates that CXCR4 exhibits some degree of ligand-independent activity, a relevant feature for drug development. SIGNIFICANCE STATEMENT: The CXCL12/CXCR4 axis represents a well-established therapeutic target for cancer treatment. We demonstrate that CXCR4 exhibits a multifaceted response that involves dynamic receptor dimer rearrangements, which is kinetically embedded between receptor-G protein complex rearrangements and G protein activation. The alternative endogenous ligand MIF behaves opposite to CXCL12 in each assay studied and does not lead to G protein activation. This detailed understanding of the receptor activation may aid in the development of more specific drugs against this target

Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists

Using the available structural information of the chemokine receptor CXCR4, we present hit finding and hit exploration studies that make use of virtual fragment screening, design, synthesis and structure-activity relationship (SAR) studies. Fragment 2 was identified as virtual screening hit and used as a starting point for the exploration of 31 N-substituted piperidin-4-yl-methanamine derivatives to investigate and improve the interactions with the CXCR4 binding site. Additionally, subtle structural ligand changes lead to distinct interactions with CXCR4 resulting in a full to partial displacement of CXCL12 binding and competitive and/or non-competitive antagonism. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and binding model studies were used to identify important hydrophobic interactions that determine binding affinity and indicate key ligand-receptor interactions

Women and power: a theoretical approach using the example of copreneurial businesses

Despite the gradual recognition of strategic issues related to the integration of women into the economy, female entrepreneurship continues to receive little attention. Family business research attributes this situation to a lack of recognition given to the (decisive) role of women in these organizations. However, there is one type of family governance that formally acknowledges the man/woman combination: the copreneurial company. Copreneurs are couples who run a business together. This theoretical article highlights the role of women in the copreneurial context by distinguishing between formal and informal power- the latter being primarily held by women, but which is no less influential. The distribution of power reduces opposition costs between partners and the social costs of non-compliance, and improves the clarity of the entrepreneurial structure. Moreover, it increases satisfaction and a feeling of equality between the partners. These results can be generalized and shed light on the role of women in other entrepreneurial and social contexts. This article is published as part as part of a collection on the role of women in management and business

Constitution et organisation de l'artisanat dans la France contemporaine

[fre] L'aide de l'Etat (contribution matérielle à l'organisation du groupe, reconnaissance juridique du groupe et création d'institutions propres, mesures diverses favorables aux artisans et motivant les agents à se faire connaître comme tels : mesures créant des intérêts communs, déjà celui de les maintenir ou de les améliorer), dans la conjoncture de l'entre-deux guerres où l'organisation des classes moyennes constitue un rempart contre le socialisme porté par les organisations de la classe ouvrière, permet à des représentants d'un groupe à constituer, avec lesquels l'Etat collabore, de rassembler ses membres potentiels, de leur dire qu'ils sont des artisans, de forger une identité sociale nouvelle, en s'appuyant sur l'identité de métier, encore que des conceptions correspondant à des idéologies, à des alliances politiques et, en définitive, à des intérêts économiques différents s'affrontent et que l'une d'entre elles finit par l'emporter, en 1938. [eng] In the interwar period, organizing the middle classes is seen as a bulwork against socialism of the working classes. The idea is to build up a group, to assemble its potential members and tell them they are craftsmen, thus creating a new social identity. The State can then help them build their own institutions, give them official recognition and grant various advantages to them. Group spirit and common interests are thus created. In fact there is no real job unity among artisans ; their ideologies, political alliances and economic interests are diverse. In 1938, however, one of the tendencies becomes dominant.

The effect of heterogeneity on HIV prevention trials

ArticleBackground: Randomized controlled trials (RCTs) for the prevention of HIV heterosexual acquisition are usually conducted among adult African populations with high heterogeneity in individual risk of infection. Purpose: The objectives were to (a) review how this heterogeneity has been considered when designing and interpreting such RCTs, (b) evaluate its effect on the findings and the statistical power of these trials, and (c) assess the potential advantages of using the crossover design with single failure-time endpoint. Methods: Individual-level HIV prevention RCTs conducted in Africa and published in the period 1998-2008 were reviewed. Using Monte Carlo simulations and statistical calculations, we assessed the effect of heterogeneity on the findings and the statistical power of HIV prevention RCTs. Results: All reviewed RCTs used the parallel design. The heterogeneity in individual risk of infection within study sites was not used for stratification nor generally considered in the design and interpretation of RCTs. Simulations showed that in the context of high HIV incidence, high heterogeneity can lead to a substantial underestimation of the impact of an intervention and reduced statistical power. Calculations demonstrated that the crossover design allowed for similar or better estimation and statistical power. The crossover design has the ethical advantage of sharing the potential benefits and risks of the intervention between participants. Limitations: Only trials with two treatment arms and two follow-up periods were modeled. The baseline risk of infection of each participant was assumed to be constant over time and HIV status was assessed at the end of each follow-up period. Conclusions: The heterogeneity in individual risk of HIV infection is an underestimated problem which should be taken into account when designing and interpreting RCTs that test prevention methods of HIV heterosexual acquisition in adult African populations with high HIV incidence. When the effects of tested interventions are rapidly reversible, the use of the crossover design should be considered. © The Author(s), 2011

Integration of stable ionic liquid-based nanofluids into polymer membranes. Part II: gas separation properties toward fluorinated greenhouse gases

Membrane technology can play a very influential role in the separation of the constituents of HFC refrigerant gas mixtures, which usually exhibit azeotropic or near-azeotropic behavior, with the goal of promoting the reuse of value-added compounds in the manufacture of new low-global warming potential (GWP) refrigerant mixtures that abide by the current F-gases regulations. In this context, the selective recovery of difluorometane (R32, GWP = 677) from the commercial blend R410A (GWP = 1924), an equimass mixture of R32 and pentafluoroethane (R125, GWP = 3170), is sought. To that end, this work explores for the first time the separation performance of novel mixed-matrix membranes (MMMs) functionalized with ioNanofluids (IoNFs) consisting in a stable suspension of exfoliated graphene nanoplatelets (xGnP) into a fluorinated ionic liquid (FIL), 1-ethyl-3-methylpyridinium perfluorobutanesulfonate ([C2C1py][C4F9SO3]). The results show that the presence of IoNF in the MMMs significantly enhances gas permeation, yet at the expense of slightly decreasing the selectivity of the base polymer. The best results were obtained with the MMM containing 40 wt% IoNF, which led to an improved permeability of the gas of interest (PR32 = 496 barrer) with respect to that of the neat polymer (PR32 = 279 barrer) with a mixed-gas separation factor of 3.0 at the highest feed R410A pressure tested. Overall, the newly fabricated IoNF-MMMs allowed the separation of the near-azeotropic R410A mixture to recover the low-GWP R32 gas, which is of great interest for the circular economy of the refrigeration sector.European Regional Development Fund | Ref. KET4F-Gas-SOE2/P1/P0823Agencia Estatal de Investigación | Ref. PID2019-105827RB-I00/ AEI / 10.13039/501100011033Ministerio de Ciencia, Innovación y Universidades | Ref. FJCI-2017-32884Laboratório Associado para a Química Verde | Ref. FCT/MCTES UIDB/50006/202