Joblessness

The U.S. labor market has been experiencing unprecedented high average unemployment duration. The shift in the unemployment duration distribution can be traced back to the early nineties. In this paper, censored quantile regression methods are employed to analyze the changes in the US unemployment duration distribution. We explore the decomposition method proposed by Machado and Mata (2005) to disentangle the contribution of compositional vis-à-vis structural changes. The data used in this inquiry are taken from the nationally representative Displaced Worker Surveys of 1988 and 2008. Apart from the effect of economic improvement we find that the sensitivity of joblessness duration to education and the aging of the population were the two main forces behind the increase of the unemployment duration, in the last twenty years. We tentatively argue that firms use education as a signaling device during recessions, but the signaling power of education during the recent low-unemployment environment faded significantly.

a quantitative approach

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a quantitative approach

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In Situ AFM Imaging of Adsorption Kinetics of DPPG Liposomes: A Quantitative Analysis of Surface Roughness

IF/00808/2013 (POPH, UE-FSE). M.R. acknowledges the financial support from the project PTDC/FIS-NAN/0909/2014, FCT, Portugal.The adsorption of intact liposomes on surfaces is of great importance for the development of sensors and drug delivery systems and, also, strongly dependent on the surface roughness where the liposomes are adsorbed. In this paper, we analyzed, by using atomic force microscopy in liquid, the evolution of the morphology of gold surfaces and of poly(allylamine hydrochloride) (PAH) surfaces with different roughness during the adsorption of liposomes prepared with the synthetic phospholipid 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]. Our results reveal the following. On smooth surfaces of Au only and Au with PAH, the liposomes open and deploy on the substrate, creating a supported-lipid bilayer, with the opening process being faster on the Au/PAH surface. On rough substrates of Au coated with polyelectrolyte multilayers, the liposomes were adsorbed intact on the surface. This was corroborated by power spectral density analysis that demonstrates the presence of superstructures with an average lateral size of 43 and 87 nm, in accordance with two and four times the mean liposome hydrodynamic diameter of about 21 nm. In addition, this work presents an adequate and effective methodology for analysis of adsorption phenomena of liposomes on rough surfaces.preprintepub_ahead_of_prin

Synthesis and screening of antibacterial activity of 2,4,5-tri(hetero)arylimidazoles based on thieno[3,2-b]thiophene

After the discovery of antibiotics, efforts were made to develop new drugs in order to treat infections caused by a wide range of bacterial strains. With the use of antibiotics for decades, bacteria have adapted, so that resistant strains have emerged. Moreover, the uncontrolled and abusive use of antibiotics has increased, which aggravates the emergence of new resistant strains. The emergence of multidrug resistant (MDR) bacteria has quickly become a worldwide health problem, so new strategies must be developed in order to control MDR bacteria, namely the rational development of new drugs. Imidazole derivatives have several biological activities, including antibacterial activity. In this sense, efforts have been made to develop imidazole-based compounds, because they present higher curative effect than other antibiotics used in clinical practice, lower toxicity and less side effects.1 With this in mind, we report the synthesis of two 2,4,5-tri(hetero)arylimidazoles 3a-b based on thieno[3,2-b]thiophene heterocyclic spacer (Figure 1), through the Radziszewski reaction2 and their characterization by 1H and 13C NMR, UV-Vis absorption and fluorescence spectroscopies. In addition, a screening for antibacterial activity with the synthetized imidazole derivatives against Bacillus subtilis was carried out, using the agar diffusion technique. The results showed the inhibition of Bacillus subtilis proliferation, suggesting antibacterial activity. Therefore, these new imidazole derivatives have the potential for the development of new antibacterial drugs.Thanks are due to Fundação para a Ciência e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU for financial support through the Chemistry Research Centre of the University of Minho (UID/QUI/00686/2020). This work was also supported by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. Thanks are also due to FCT for financial support to the Portuguese NMR network (PTNMR, Bruker Avance III – Univ. Minho).info:eu-repo/semantics/publishedVersio

New non-toxic n-alkyl cholinium-based ionic liquids as excipients to improve the solubility of poorly water-soluble drugs

Funding Information: Funding: The authors thank Fundação para a Ciência e Tecnologia, FCT/MCTES (Portugal) for financial support through investigator contract (IF/00621/2015—P.M. Reis) and project IF/00621/2015. This work was also supported by the Associate Laboratory for Green Chemistry—LAQV (UIDB/50006/2020 and UIDP/50006/2020) and by projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB, which are financed by national funds from FCT/MCTES. The NMR spectrometers at FCT-NOVA are part of Rede Nacional de RMN (PTNMR), supported by FCT-MCTES (ROTEIRO/0031/2013—PINFRA/22161/2016) (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). LRR acknowledges FCT/MCTES project PTDC/CVT-EPI/6685/2014.In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclo-fenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional1H/1H nuclear overhauser effect spectroscopy (NO-ESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two inter-molecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.publishersversionpublishe

The Unique Lipidomic Signatures of Saccharina latissima Can Be Used to Pinpoint Their Geographic Origin

The aquaculture of macroalgae for human consumption and other high-end applications is experiencing unprecedented development in European countries, with the brown algae Saccharina latissima being the flag species. However, environmental conditions in open sea culture sites are often unique, which may impact the biochemical composition of cultured macroalgae. The present study compared the elemental compositions (CHNS), fatty acid profiles, and lipidomes of S. latissima originating from three distinct locations (France, Norway, and the United Kingdom). Significant differences were found in the elemental composition, with Norwegian samples displaying twice the lipid content of the others, and significantly less protein (2.6%, while French and UK samples contained 6.3% and 9.1%, respectively). The fatty acid profiles also differed considerably, with UK samples displaying a lower content of n-3 fatty acids (21.6%), resulting in a higher n-6/n-3 ratio. Regarding the lipidomic profile, samples from France were enriched in lyso lipids, while those from Norway displayed a particular signature of phosphatidylglycerol, phosphatidylinositol, and phosphatidylcholine. Samples from the UK featured higher levels of phosphatidylethanolamine and, in general, a lower content of galactolipids. These differences highlight the influence of site-specific environmental conditions in the shaping of macroalgae biochemical phenotypes and nutritional value. It is also important to highlight that differences recorded in the lipidome of S. latissima make it possible to pinpoint specific lipid species that are likely to represent origin biomarkers. This finding is relevant for future applications in the field of geographic origin traceability and food controlpublishedVersio

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion

Funding Information: This work was funded by: i) national funds through FCT - Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center - UnIC (UIDB/00051/2020 and UIDP/00051/2020); ii) “la Caixa” Banking Foundation and FCT under the project code LCF/PR/HP17/52190002”; iii) the QREN project 2013/30196; and iv) the European Structural and Investment Funds (ESIF), under the Lisbon Portugal Regional Operational Program and National Funds through FCT [POCI-01-0145-FEDER-030985]. RNG and TLL were funded by the FCT individual fellowships [SFRH/BD/144490/2019] and [PD/BD/127997/2016], respectively. Funding sources had no interference in the design of the study, study governance, data collection and analysis, nor in manuscript writing or its scientific and intellectual content. Publisher Copyright: 2023 Raposo, Cerqueira, Leite, Moreira-Costa, Laundos, Miranda, Mendes-Ferreira, Coelho, Gomes, Pinto-do-Ó, Nascimento, Lourenço, Cardim and Leite-Moreira.Background: Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. Methods: In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. Results: As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = −2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Conclusion: Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.publishersversionpublishe

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion

BackgroundHuman umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine.MethodsIn a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing.ResultsAs compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = −2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC.ConclusionIntracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect