Social impact analysis of products under a holistic approach: A case study in the meat product supply chain

Social impact assessment of products can be approached through different methodologies that need to be adapted to the particularities and features of the studied subject. Thus, the Social Life Cycle Assessment methodology can be used to assess different innovative practices of product manufacturing, under a circular economy approach, by identifying potential positive as well as negative impacts along products’ life cycle. This paper presents the results of the Social Life Cycle Impact Assessment of a reference product from the Spanish meat industry using existing and new innovative methods of social impact analysis. Worker discrimination, health and safety for workers, consumers and local community were identified as the social aspects with relevant significance into the business or for the influence on customer’s perception of the products studied. Therefore, results can represent a reference scenario for the future assessment of innovative solutions in the Spanish meet sector. Despite the scarce use of Social Life Cycle Impact Assessment, this case study is a good example of how this innovative kind of assessment can be helpful for companies to identify their weak and strong social performance areas and design strategies to improve in Social Responsibility Management. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

The indefinite-interrogative affinity in sign languages: the case of Catalan Sign Language

Prior studies on spoken languages have shown that indefinite and interrogative pronouns may be formally very similar. Our research aims to understand if sign languages exhibit this type of affinity. This paper presents an overview of the phenomenon and reports on the results of two studies: a cross-linguistic survey based on a sample of 30 sign languages and an empirical investigation conducted with three deaf consultants of Catalan Sign Language (LSC). Our research shows that, in sign languages, certain signs have both existential and interrogative readings and it identifies the environments that make existential interpretations available in LSC

Substitution models of protein evolution with selection on enzymatic activity

Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity. Here, we present a substitution model of protein evolution with selection on both protein structure and enzymatic activity, and that can be applied to phylogenetics. In particular, the model considers the binding affinity of the enzyme–substrate complex as well as structural constraints that include the flexibility of structural flaps, hydrogen bonds, amino acids backbone radius of gyration, and solvent-accessible surface area that are quantified through molecular dynamics simulations. We applied the model to the HIV-1 protease and evaluated it by phylogenetic likelihood in comparison with the best-fitting empirical substitution model and a structurally constrained substitution model that ignores the enzymatic activity. We found that accounting for selection on the protein activity improves the fitting of the modeled functional regions with the real observations, especially in data with high molecular identity, which recommends considering constraints on the protein activity in the development of substitution models of evolution.Agencia Estatal de Investigación | Ref. PID2019-107931GA-I00Xunta de Galicia | Ref. ED481A-2020/192Fundação para a Ciência e a TecnologiaUniversidade de Vigo/CISU

Conformationally-Locked C-Glycosides: Tuning Aglycone Interactions for Optimal Cheperone Behaviour in Gaucher Fibroblasts

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver β-glucosidase/β-galactosidase and specific inhibition of human β-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound AmbroxolMinisterio de Economía y Competitividad CTQ2012-36365, SAF2013-44021-RJunta de Andalucía FQM-1467European Union Seventh Framework Programme FP7-People-2012-CI

A projection hybrid high order finite volume/finite element method for incompressible turbulent flows

In this paper the projection hybrid FV/FE method presented in Busto et al. 2014 is extended to account for species transport equations. Furthermore, turbulent regimes are also considered thanks to the $k-\varepsilon$ model. Regarding the transport diffusion stage new schemes of high order of accuracy are developed. The CVC Kolgan-type scheme and ADER methodology are extended to 3D. The latter is modified in order to profit from the dual mesh employed by the projection algorithm and the derivatives involved in the diffusion term are discretized using a Galerkin approach. The accuracy and stability analysis of the new method are carried out for the advection-diffusion-reaction equation. Within the projection stage the pressure correction is computed by a piecewise linear finite element method. Numerical results are presented, aimed at verifying the formal order of accuracy of the scheme and to assess the performance of the method on several realistic test problems.Comment: arXiv admin note: text overlap with arXiv:1802.1058

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD–ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein

MIMAC: MIcro-tpc MAtrix of Chambers for dark matter directional detection

Directional detection of non-baryonic Dark Matter is a promising search strategy for discriminating WIMP events from neutrons, the ultimate background for dark matter direct detection. This strategy requires both a precise measurement of the energy down to a few keV and 3D reconstruction of tracks down to a few mm. The MIMAC (MIcro-tpc MAtrix of Chambers) collaboration has developed in the last years an original prototype detector based on the direct coupling of large pixelized micromegas with a special developed fast self-triggered electronics showing the feasibility of a new generation of directional detectors. The first bi-chamber prototype has been installed at Modane, underground laboratory in June 2012. The first undergournd background events, the gain stability and calibration are shown. The first spectrum of nuclear recoils showing 3D tracks coming from the radon progeny is presented.Comment: Proceedings of the 4th International Conference on Directional Dark Matter Detection CYGNUS2013, held in Toyoma (Japan), June 201

Anticancer and antibacterial potential of robust Ruthenium(II) arene complexes regulated by choice of α-diimine and halide ligands

Several complexes of general formula [Ru(halide)(η6-p-cymene)(α-diimine)]+, in the form of nitrate, triflate and hexafluorophosphate salts, including a newly synthesized iodide compound, were investigated as potential anticancer drugs and bactericides. NMR and UV–Vis studies evidenced remarkable stability of the complexes in water and cell culture medium. In general, the complexes displayed strong cytotoxicity against A2780 and A549 cancer cell lines with IC50 values in the low micromolar range, and one complex (RUCYN) emerged as the most promising one, with a significant selectivity compared to the non-cancerous HEK293 cell line. A variable affinity of the complexes for BSA and DNA binding was ascertained by spectrophotometry/fluorimetry, circular dichroism, electrophoresis and viscometry. The performance of RUCYN appears associated to enhanced cell internalization, favored by two cyclohexyl substituents, rather than to specific interaction with the evaluated biomolecules. The chloride/iodide replacement, in one case, led to increased cellular uptake and cytotoxicity at the expense of selectivity, and tuned DNA binding towards intercalation. Complexes with iodide or a valproate bioactive fragment exhibited the best antimicrobial profiles