Corrections to the SU(3)×SU(3){\bf SU(3)\times SU(3)} Gell-Mann-Oakes-Renner relation and chiral couplings L8rL^r_8 and H2rH^r_2

Next to leading order corrections to the $SU(3) \times SU(3)$ Gell-Mann-Oakes-Renner relation (GMOR) are obtained using weighted QCD Finite Energy Sum Rules (FESR) involving the pseudoscalar current correlator. Two types of integration kernels in the FESR are used to suppress the contribution of the kaon radial excitations to the hadronic spectral function, one with local and the other with global constraints. The result for the pseudoscalar current correlator at zero momentum is $\psi_5(0) = (2.8 \pm 0.3) \times 10^{-3} GeV^{4}$, leading to the chiral corrections to GMOR: $\delta_K = (55 \pm 5)$. The resulting uncertainties are mostly due to variations in the upper limit of integration in the FESR, within the stability regions, and to a much lesser extent due to the uncertainties in the strong coupling and the strange quark mass. Higher order quark mass corrections, vacuum condensates, and the hadronic resonance sector play a negligible role in this determination. These results confirm an independent determination from chiral perturbation theory giving also very large corrections, i.e. roughly an order of magnitude larger than the corresponding corrections in chiral $SU(2) \times SU(2)$. Combining these results with our previous determination of the corrections to GMOR in chiral $SU(2) \times SU(2)$, $\delta_\pi$, we are able to determine two low energy constants of chiral perturbation theory, i.e. $L^r_8 = (1.0 \pm 0.3) \times 10^{-3}$, and $H^r_2 = - (4.7 \pm 0.6) \times 10^{-3}$, both at the scale of the $\rho$-meson mass.Comment: Revised version with minor correction

Leishmania infantum UBC1 in Metacyclic Promastigotes from Phlebotomus perniciosus, a Vaccine Candidate for Zoonotic Visceral Leishmaniasis

Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species' life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the Leishmania infantum ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against L. infantum infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against L. infantum in the Syrian hamster model.This work was financed by a contract with CZ Vaccines, Porriño, Spain, and partially defrayed by a grant from the Fundación Ramón Areces. JL thanks CZ Vaccines for the fellowship.S

Corrosion resistance of anodic layers grown on 304L stainless steel at different anodizing times and stirring speeds

Different chemical and physical treatments have been used to improve the properties and functionalities of steels. Anodizing is one of the most promising treatments, due to its versatility and easy industrial implementation. It allows the growth of nanoestructured oxide films with interesting properties able to be employed in different industrial sectors. The present work studies the influence of the anodizing time (15, 30, 45 and 60 min), as well as the stirring speed (0, 200, 400, and 600 rpm), on the morphology and the corrosion resistance of the anodic layers grown in 304L stainless steel. The anodic layers were characterized morphologically, compositionally, and electrochemically, in order to determine the influence of the anodization parameters on their corrosion behavior in a 0.6 mol L-1 NaCl solution. The results show that at 45 and 60 min anodizing times, the formation of two microstructures is favored, associated with the collapse of the nanoporous structures at the metal-oxide interphace. However, both the stirring speed and the anodizing time have a negligeable effect on the corrosion behavior of the anodized 304L SS samples, since their electrochemical values are similar to those of the non-anodized ones

Proteomic profiling of stallion spermatozoa suggests changes in sperm metabolism and compromised redox regulation after cryopreservation

Proteomic technologies allow the detection of thousands of proteins at the same time, being a powerful technique to reveal molecular regulatory mechanisms in spermatozoa and also sperm damage linked to low fertility or specific biotechnologies. Modifications induced by the cryopreservation in the stallion sperm proteome were studied using UHPLC/MS/MS. Ejaculates from fertile stallions were collected and split in two subsamples, one was investigated as fresh (control) samples, and the other aliquot frozen and thawed using standard procedures and investigated as frozen thawed subsamples. UHPLC/MS/MS was used to study the sperm proteome under these two distinct conditions and bioinformatic enrichment analysis conducted. Gene Ontology (GO) and pathway enrichment analysis were performed revealing dramatic changes as consequence of cryopreservation. The terms oxidative phosphorylation, mitochondrial ATP synthesis coupled electron transport and electron transport chain were significantly enriched in fresh samples (P = 5.50 × 10−12, 4.26 × 10−8 and 7.26 × 10–8, respectively), while were not significantly enriched in frozen thawed samples (P = 1). The GO terms oxidation reduction process and oxidoreductase activity were enriched in fresh samples and the enrichment was reduced in frozen thawed samples (1.40 × 10−8, 1.69 × 10−6 versus 1.13 × 10−2 and 2-86 × 10−2 respectively). Reactome pathways (using human orthologs) significantly enriched in fresh sperm were TCA cycle and respiratory electron transport (P = 1.867 × 10−8), Respiratory electron transport ATP synthesis by chemiosmosis coupling (P = 2.124 × 10−5), Citric acid cycle (TCA cycle)(P = 8.395 × 10−4) Pyruvate metabolism and TCA cycle (P = 3.380 × 10−3), Respiratory electron transport (P = 2.764 × 10−2) and Beta oxidation of laurolyl-CoA to decanoyl CoA-CoA (P = 1.854 × 10−2) none of these pathways were enriched in thawed samples (P = 1). We have provided the first detailed study on how the cryopreservation process impacts the stallion sperm proteome. Our findings identify the metabolic proteome and redoxome as the two key groups of proteins affected by the procedure. Significance: In the present manuscript we investigated how the cryopreservation of stallion spermatozoa impacts the proteome of these cells. This procedure is routinely used in horse breeding and has a major impact in the industry, facilitating the trade of genetic material. This is still a suboptimal biotechnology, with numerous unresolved problems. The limited knowledge of the molecular insults occurring during cryopreservation is behind these problems. The application and development of proteomics to the spermatozoa, allow to obtain valuable information of the specific mechanisms affected by the procedure. In this paper, we report that cryopreservation impacts numerous proteins involved in metabolism regulation (mainly mitochondrial proteins involved in the TCA cycle, and oxidative phosphorylation) and also affects proteins with oxidoreductase activity. Moreover, specific proteins involved in the sperm-oocyte interaction are also affected by the procedure. The information gathered in this study, opens interesting questions and offer new lines of research for the improvement of the technology focusing the targets here identified, and the specific steps in the procedure (cooling, toxicity of antioxidants etc.) to be modified to reduce the damage

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Background: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. Methods: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDGPET/CT focusing on several territories’ vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. Results: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. Conclusions: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory

Computational Approaches to Explainable Artificial Intelligence:Advances in Theory, Applications and Trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9 International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications

Imaging mass cytometry analysis of Becker muscular dystrophy muscle samples reveals different stages of muscle degeneration

\ua9 2024. The Author(s). Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle. We developed a software for analysing IMC images and studied changes in the muscle composition and spatial correlations between markers across disease progression. We found a strong correlation between collagen-I and the area of stroma, collagen-VI, adipose tissue, and M2-macrophages number. There was a negative correlation between the area of collagen-I and the number of satellite cells (SCs), fibres and blood vessels. The comparison between fibrotic and non-fibrotic areas allowed to study the disease process in detail. We found structural differences among non-fibrotic areas from control and patients, being these latter characterized by increase in CTGF and in M2-macrophages and decrease in fibers and blood vessels. IMC enables to study of changes in tissue structure along disease progression, spatio-temporal correlations and opening the door to better understand new potential pathogenic pathways in human samples

Increased lytic efficiency of bovine macrophages trained with killed mycobacteria

Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.Funding for these studies was provided by the EU project WildTBVac (Contract #613799) and by grants from the Instituto Nacional de Investigación y Tecnología Agraria y alimentaria (INIA, RTA2011-00049) and the Ministry of Science (MINECO, AGL2014-56305) and European Funds Regional Development (FEDER).Peer Reviewe

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13