Deformation heterogeneity study of a 6061-T6 aluminum alloy processed by equal channel angular pressing

Among the severe plastic deformation techniques, the equal channel angular pressing (ECAP) has drastically improved the mechanical properties of the processed alloys. However, information regarding friction phenomenon, which modifies the deformation at the surface and the heterogeneity microstrain state produced by the process itself, is still scarce. In the present work, the deformation heterogeneity and the friction effect, at the surface in the bulk material of the 6061-T6 aluminum alloy processed by ECAP, is presented and discussed. The residual stress (RS) measurements were performed by means of X-Ray diffraction. By means of synchrotron diffraction, volumetric sections of the ECAPed samples were characterized. Finite element analysis showed a good agreement with the experimentally obtained residual stress and microhardness mapping results. The study also showed that the highest deformation zones were located at the outer parts of the deformed samples (top and bottom), while the inner zone showed strain oscillations of up to 49±2 MPa.Peer ReviewedPostprint (author's final draft

Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population

Indexación: Web of ScienceBackground MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population. Results We evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01). Conclusions The contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.http://bmcgenet.biomedcentral.com/articles/10.1186/s12863-016-0415-

ChaLearn Looking at People Challenge 2014: Dataset and Results

This paper summarizes the ChaLearn Looking at People 2014 challenge data and the results obtained by the participants. The competition was split into three independent tracks: human pose recovery from RGB data, action and interaction recognition from RGB data sequences, and multi-modal gesture recognition from RGB-Depth sequences. For all the tracks, the goal was to perform user-independent recognition in sequences of continuous images using the overlapping Jaccard index as the evaluation measure. In this edition of the ChaLearn challenge, two large novel data sets were made publicly available and the Microsoft Codalab platform were used to manage the competition. Outstanding results were achieved in the three challenge tracks, with accuracy results of 0.20, 0.50, and 0.85 for pose recovery, action/interaction recognition, and multi-modal gesture recognition, respectively

HCV microelimination in harm reduction centres has benefits beyond HCV cure but is hampered by high reinfection rates

Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices.On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment.Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness.HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates.People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.© 2022 The Author(s)

Lymphoid B cells induce NF-κB activation in high endothelial cells from human tonsils

Indexación: Scopus.Immune surveillance depends on still poorly understood lymphocyte-endothelium interactions required for lymphocyte transendothelial migration into secondary lymphoid organs. The nuclear factor κB (NF-κB) regulatory system and its inhibitory IκB proteins control the inducible expression of adhesion molecules, cytokines and chemokines involved in endothelial activation and lymphocyte transmigration. Here we present results showing the activation of this system in response to the interaction of high endothelial cells from human tonsils (HUTEC) with human B and T lymphoid cell lines and primary tonsillar lymphocytes. Western blot and electrophoretic mobility shift assays show that adhesion of different lymphoid cells induce varying levels of NF-κB activation in HUTEC, with Daudi cells, tonsil-derived B cell line 10 (TBCL-10) and primary tonsillar B lymphocytes causing the strongest activation. The main NF-κB protein complexes translocated to the nucleus were p65/p50 and p50/p50. Results from reverse transcription-PCR and flow cytometry analysis of HUTEC indicate that the interaction with Daudi cells induce an increased expression of IL-6 and IL-8 mRNA and cell-surface expression of intercellular adhesion molecule-1, all of which were prevented by sodium salicylate, an inhibitor of NF-κB activation. Transwell experiments show that NF-κB activation and the response of HUTEC to the interaction of Daudi cells does not depend on direct cell-cell contact but rather on the production of soluble factors that require the presence of both cell types. These results suggest that lymphocytes and high endothelium establish a cross talk leading to NF-κB-mediated expression of cytokines and adhesion molecules, inducing endothelial cell activation.https://academic.oup.com/intimm/article/18/2/259/66453

Persistence of Li Induced Kondo Moments in the Superconducting State of Cuprates

We measure the magnetic susceptibility nearby Li spinless impurities in the superconducting phase of the high Tc cuprate YBaCuO. The induced moment which was found to exist above Tc persists below Tc. In the underdoped regime, it retains its Curie law below Tc. In contrast, near optimal doping, the large Kondo screening observed above Tc (T_K=135 K) is strongly reduced below Tc as expected theoretically when the superconducting gap develops. This moment still extends essentially on its 4 near neighbour Cu, showing the persistence of AF correlations in the superconducting state. A direct comparison with recent STM results of Pan et al. is proposed.Comment: accepted for publication in Phys. Rev. Lett. (issue of 30 april 2001) Revised version : 8 pages including 4 pages of text and 4 figure

Controlled sulfur-based engineering confers mouldability to phosphorothioate antisense oligonucleotides

Phosphorothioates (PS) have proven their effectiveness in the area of therapeutic oligonucleotides with applications spanning from cancer treatment to neurodegenerative disorders. Initially, PS substitution was introduced for the antisense oligonucleotides (PS ASOs) because it confers an increased nuclease resistance meanwhile ameliorates cellular uptake and in-vivo bioavailability. Thus, PS oligonucleotides have been elevated to a fundamental asset in the realm of gene silencing therapeutic methodologies. But, despite their wide use, little is known on the possibly different structural changes PS-substitutions may provoke in DNA·RNA hybrids. Additionally, scarce information and significant controversy exists on the role of phosphorothioate chirality in modulating PS properties. Here, through comprehensive computational investigations and experimental measurements, we shed light on the impact of PS chirality in DNA-based antisense oligonucleotides; how the different phosphorothioate diastereomers impact DNA topology, stability and flexibility to ultimately disclose pro-Sp S and pro-Rp S roles at the catalytic core of DNA Exonuclease and Human Ribonuclease H; two major obstacles in ASOs-based therapies. Altogether, our results provide full-atom and mechanistic insights on the structural aberrations PS-substitutions provoke and explain the origin of nuclease resistance PS-linkages confer to DNA·RNA hybrids; crucial information to improve current ASOs-based therapies.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research

What have we learnt from EUPORIAS climate service prototypes?

The international effort toward climate services, epitomised by the development of the Global Framework for Climate Services and, more recently the launch of Copernicus Climate Change Service has renewed interest in the users and the role they can play in shaping the services they will eventually use. Here we critically analyse the results of the five climate service prototypes that were developed as part of the EU funded project EUPORIAS. Starting from the experience acquired in each of the projects we attempt to distil a few key lessons which, we believe, will be relevant to the wider community of climate service developers

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer