250 research outputs found

    A fresh look at the (non-)Abelian Landau-Khalatnikov-Fradkin transformations

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    The Landau-Khalatnikov-Fradkin transformations (LKFTs) allow to interpolate nn-point functions between different gauges. We first offer an alternative derivation of these LKFTs for the gauge and fermions field in the Abelian (QED) case when working in the class of linear covariant gauges. Our derivation is based on the introduction of a gauge invariant transversal gauge field, which allows a natural generalization to the non-Abelian (QCD) case of the LKFTs. To our knowledge, within this rigorous formalism, this is the first construction of the LKFTs beyond QED. The renormalizability of our setup is guaranteed to all orders. We also offer a direct path integral derivation in the non-Abelian case, finding full consistency.Comment: 16 page

    Homotopy data as part of the lattice field: A first study

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    Fields exhibit a variety of topological properties, like different topological charges, when field space in the continuum is composed by more than one topological sector. Lattice treatments usually encounter difficulties describing those properties. In this work, we show that by augmenting the usual lattice fields to include extra variables describing local topological information (more precisely, regarding homotopy), the topology of the space of fields in the continuum is faithfully reproduced in the lattice. We apply this extended lattice formulation to some simple models with non-trivial topological charges, and we study their properties both analytically and via Monte Carlo simulations.Comment: We added some references and a section where we make contact between the extended lattice formalism and the usual lattice variables augmented with an integer lattice field in the dual lattice. We made some corrections, including changing the title and the abstract, after referee's corrections and critique

    Transcriptional control of the B3GALT5 gene by a retroviral promoter and methylation of distant regulatory elements

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    We focused on transcription factors and epigenetic marks that regulate the B3GALT5 gene through its retroviral long terminal repeat (LTR) promoter. We compared the expression levels of the B3GALT5 LTR transcript, quantitated by competitive RT-PCR, with those of the candidate transcription factors HNF1\u3b1/\u3b2 and Cdx1/2, determined by Western blot analysis, in colon cancer biopsies, various cell lines, and cell models serving as controls. We found that HNF1\u3b1/\u3b2 were easily detected, irrespective of the amount of LTR transcript expressed by the source, whereas Cdx1/2 were undetectable, and no sample lacking HNF1\u3b1/\u3b2 expressed the LTR transcript. On transfection in proper host cells, both HNF1\u3b1 and HNF1\u3b2 provided detectable LTR transcript, whereas shRNA-mediated silencing of HNF1\u3b2 impaired transcription. Treating cells with 5\u2032-aza-2\u2032-deoxycytidine (5AZA) strongly reduced expression, without affecting HNF1\u3b1/\u3b2, despite the lack of CpG islands in the LTR and proximal sequences. By electrophoresis mobility shift and luciferase reporter assays, the LTR promoter binding and activity did not correlate with the amounts of LTR transcript expressed in the cells and depended on the levels of the transcription factors. We conclude that HNF1\u3b1/\u3b2 are necessary but insufficient to activate and regulate B3GALT5 LTR transcription, which depends on unknown regulatory elements that are active when methylated and located outside of and far from the LTR promoter

    Methanol masers reveal the magnetic field of the high-mass protostar IRAS 18089-1732

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    Context. The importance of the magnetic field in high-mass-star formation is not yet fully clear and there are still many open questions concerning its role in the accretion processes and generation of jets and outflows. In the past few years, masers have been successfully used to probe the magnetic field morphology and strength at scales of a few au around massive protostars, by measuring linear polarisation angles and Zeeman splitting. The massive protostar IRAS 18089-1732 is a well studied high-mass-star forming region, showing a hot core chemistry and a disc-outflow system. Previous SMA observations of polarised dust revealed an ordered magnetic field oriented around the disc of IRAS 18089-1732. Aims. We want to determine the magnetic field in the dense region probed by 6.7 GHz methanol maser observations and compare it with observations in dust continuum polarisation, to investigate how the magnetic field in the compact maser region relates to the large-scale field around massive protostars. Methods. We reduced MERLIN observations at 6.7 GHz of IRAS 18089-1732 and we analysed the polarised emission by methanol masers. Results. Our MERLIN observations show that the magnetic field in the 6.7 GHz methanol maser region is consistent with the magnetic field constrained by the SMA dust polarisation observations. A tentative detection of circularly polarised line emission is also presented. Conclusions. We found that the magnetic field in the maser region has the same orientation as in the disk. Thus the large-scale field component, even at the au scale of the masers, dominates over any small-scale field fluctuations. We obtained, from the circular polarisation tentative detection, a field strength along the line of sight of 5.5 mG which appeared to be consistent with the previous estimates.Comment: 12 pages, 7 figures, accepted for publication in A&

    The expanding roles of the Sda/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2

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    Background The histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sda antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups. Scope of review We describe the multiple and unsuspected aspects of the biology of the Sda antigen and its biosynthetic enzyme \u3b21,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings. Major conclusions The immunodominant sugar of the Sda antigen is a \u3b21,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sda antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model. General significance The expression of the Sda antigen has a wide impact on the physiology and the pathology of different biological systems

    Ocorrência de helmintos e protozoários em cães capturados da cidade de São João da Boa Vista-SP

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    Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

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    LPCC/Pfizer 2011. Tagus TANK award 2018 (grant no. 1/2018). SFRH/BD/100970/2014 SFRH/BPD/108686/2015The formation of distant metastasis resulting from vascular dissemination is one of the leading causes of mortality in non-small cell lung cancer (NSCLC). This metastatic dissemination initiates with the adhesion of circulating cancer cells to the endothelium. The minimal requirement for the binding of leukocytes to endothelial E-selectins and subsequent transmigration is the epitope of the fucosylated glycan, sialyl Lewis x (sLex), attached to specific cell surface glycoproteins. sLex and its isomer sialyl Lewis a (sLea) have been described in NSCLC, but their functional role in cancer cell adhesion to endothelium is still poorly understood. In this study, it was hypothesised that, similarly to leukocytes, sLe glycans play a role in NSCLC cell adhesion to E-selectins. To assess this, paired tumour and normal lung tissue samples from 18 NSCLC patients were analyzed. Immunoblotting and immunohistochemistry assays demonstrated that tumour tissues exhibited significantly stronger reactivity with anti‑sLex/sLea antibody and E-selectin chimera than normal tissues (2.2- and 1.8-fold higher, respectively), as well as a higher immunoreactive score. High sLex/sLea expression was associated with bone metastasis. The overall α1,3-fucosyltransferase (FUT) activity was increased in tumour tissues, along with the mRNA levels of FUT3, FUT6 and FUT7, whereas FUT4 mRNA expression was decreased. The expression of E-selectin ligands exhibited a weak but significant correlation with the FUT3/FUT4 and FUT7/FUT4 ratios. Additionally, carcinoembryonic antigen (CEA) was identified in only 8 of the 18 tumour tissues; CEA-positive tissues exhibited significantly increased sLex/sLea expression. Tumour tissue areas expressing CEA also expressed sLex/sLea and showed reactivity to E-selectin. Blot rolling assays further demonstrated that CEA immunoprecipitates exhibited sustained adhesive interactions with E-selectin-expressing cells, suggesting CEA acts as a functional protein scaffold for E-selectin ligands in NSCLC. In conclusion, this work provides the first demonstration that sLex/sLea are increased in primary NSCLC due to increased α1,3-FUT activity. sLex/sLea is carried by CEA and confers the ability for NSCLC cells to bind E-selectins, and is potentially associated with bone metastasis. This study contributes to identifying potential future diagnostic/prognostic biomarkers and therapeutic targets for lung cancer.preprintpublishe

    CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors

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    Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit. Materials and methods: This is a retrospective cohort study including patients with stage IIIB–IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well. Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 >8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24–2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04–0.33; p < 0.001), and for CYFRA 21-1 (HR 0.19; 95% CI 0.07–0.55; p 0.002) Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit

    Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

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    Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases
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