1,721,102 research outputs found
Burkitt Lymphoma: from B-Cell Receptor activation to Tumor Microenvironment
Full text linkBackground: In Burkitt lymphoma (BL) macrophages represent the main component of TME giving rise to the characteristic histological aspect of the “starry sky” pattern. However, in some instances, BL may show a granulomatous reaction and such cases are associated with a favorable prognosis and occasionally spontaneous regression.
Objectives.The aim of the present work was to thoroughly characterize the immune landscape of BL subtypes: 7 EBV-positive BL with granulomatous reaction, 8 EBV-positive BL with the typical starry sky pattern, 8 EBV- negative BL with the typical starry sky pattern.
Design\Methods: Genes expression profiling (GEP) of 23 Formalin-Fixed Paraffin- Embedded (FFPE) samples were performed on the NanoString nCounter using the PanCancer Immune ProfilingPanel consisting of 730 immune-related genes and 40 housekeeping genes.
Results: Based on unsupervised clustering of differentially expressed genes (DEGs) BL samples formed separated clusters, distinguishing EBV-positive BL with granulomatous reaction (cluster 1) from BL with typical starry sky, both EBV-positive and EBV-negative (cluster 2 and 3, respectively). We confirmed previous findings of differently enriched genes in NF-kB, JAK-STAT, BCR signaling pathways between EBV positive BL and EBV-negative BL. In addition, differences in immune response signature were identified between BL with granulomatous reaction and BL with typical starry sky. The TME signature in BL with starry sky pattern, both EBV- positive and EBV-negative,
showed an up-regulation of M2 secreted chemokines (CCL22, CCL17, CCL2, CCR4), IL4/ IL13 pathway, M2-immune response genes (ARG1, ICOS, IDO1, LAG3, CD163, GATA3), immune checkpoint genes (CD274, PDCD1, PDCD1LG2, CTLA4) suggesting a M2- polarization in these cases. Conversely, these signatures were downregulated in BL with granulomatous reaction, resulting in a M1 polarization and a proinflammatory response.
Conclusion: Due to their pivotal role, TAMs are promising targets for additional therapies in BL lymphoma and combining TAM-targeted therapy with conventional treatment may open up novel therapeutic avenues for therapy-refractory patients.Background: BCR activation is an important step in lymphomagenesis. In different subtype of BL there is a combined mechanism of tonic and extrinsic BCR signaling activation. In eBL BCR activation can be related to the chronic Plasmodium falciparum stimulation which can reactivate latently EBV-infected memory B cells. Yet, whether coincidental infections with additional pathogens may occur in eBL remains to be addressed. On the other hand, in sBL the progressive acquisition of mutations in the TCF3/ID3 genes results in intrinsic tonic activation of BCR signaling. Therefore, neoplastic cells may grow in an EBV (and/or other antigen) independent way. Usually in Burkitt lymphomas surface IgM represents functional BCR. However high number of IgA transcript have recently reported.1 This extend previous studies showing recurrent MYC translocation breakpoints in IGHA in BL suggesting that the cell of origin of BL is a germinal center experienced B-cell primed to switch to and to express IgA. Furthermore, IgM/D/G/A-negative cases have also been reported [1]. Interestingly, heterozygous NRAS and KRAS gain of function mutations have been identified in one sample of such cases, suggesting that BL cells acquiring RAS mutations may lose the selective pressure to express a functional BCR. The aim of the present study is: a) to determines the expression of BCR by immunohistochemistry in a large series of BL b) to investigate the possible constitutive activation of the MAPK pathway through RAS mutations and c) to better understand the genetic landscape of these cases.
Materials and Methods: We performed an immunohistochemistry analysis to detect IgA/IgM/IgD/IgG expression in 72 Formalin-Fixed Paraffin-Embedded (FFPE) BL samples. We performed qPCR for RAS hotspot mutations and an NGS analysis (Illumina platform) with a capture-base custom panel covering 83 genes known to be involved in lymphomagenesis.
Results: 56/72 cases expressed surface IgM but we also found 9/72 expressing IgA. Interestingly, 7/72 lacked BCR expression, being negative for all surface immunoglobulins. BL expressing surface IgA were localized in the oral and gastrointestinal mucosa, in line with the observation that BL frequently presents in sites of the human body particularly important for IgA production.
We founded KRAS somatic mutations in the classic hotspots of the gene by qPCR in 2/5 cases lacking expression of BCR. No NRAS single nucleotide variants were identified in our cohort. NGS analysis, in addition to the typical BL’s mutations (ID3,GNA13,CCND3,MYC) showed recurrent mutations in genes not usually affected in classic BL like TET2, EZH2, HIST1H1C, HIST1H1B, PRDM1 and PIM1. Interestingly, the cases with KRAS gain of function were those with a high mutational burden,
carrying more than 5 mutation and, moreover, the only two cases of our cohort showing MYC gene mutation. EBV infection as detected in 1/2 KRAS mutated samples.
Conclusion: In this study, we confirmed the presence of RAS mutations in IgM/D/G/A-negative Burkitt lymphoma supporting the previous hypothesis2 that the constitutive RAS/MAPK activation can bypass the requirement for a functional BCR/PI3Kδ axis to sustain lymphoma fitness. Furthermore, we had demonstrated that mutation in genes related to epigenetic mechanism and histone remodeling seems to be more frequently involved in such cases
Low emittance ion beams by laser interaction
No full textLaser ion sources offer the possibility to get ion beam utilizable to improve particle accelerators. Today many laboratories, as well as the LEAS, are employed to develop accelerators of the dimensions very contained to be installed in little laboratories and hospitals. Pulsed lasers at intensities of the order of 108 W/cm2 and of ns pulse duration interacting with solid matter in vacuum, plasma of high temperature and density is produced. The charge state distribution of the plasma generates high electric fields which accelerate ions along the normal to the target surface. The energy of emitted ions has a Maxwell Boltzmann distribution which depends on the ion charge state. To increase the ion energy, a post-acceleration system can be employed by means of high voltage power supplies of about 100 kV. The post acceleration system results a good method to obtain high ion currents by a not expensive system and the final ion beams find interesting applications in the field of the ion implantations, adrotherapy, scientific applications and industrial use. In this work we compare the electromagnetic and geometric properties, like the emittanza, of the beams delivered by a Cu and Y target. The characterization of the plasma was performed by a Faraday cup for the electromagnetic characteristics, whereas a pepper pot system for the geometrical ones. At 60 kV accelerating voltage and 5.5 mA output current the normalized beam emittance resulted of 0.22 π mm mrad for the Cu target, while under the same accelerating voltage but with 7.4 mA output current a lower normalized beam emittance value was reached for the Y target. It resulted of 0.14 π mm mrad. The brightness of the beams was of 114 and 378 mA( mm mrad)-2 for the Cu and Y target, respectively. When Ag targets were utilised, we implanted an AISI 420 stainless steel by a dose of 10x1015 inos/cm2. Besides, the laser ion sources have got very good properties to feed large machines
Probe per impulsi veloci
No full textIl trovato è utile per la diagnastica di impulsi veloci. Può essere applicato per misurare fasci di corrente di ioni o elettroni, ed altro
FCD Fast Capacitive Divisor
No full textIl trovato è un divisore capacitivo di dimensioni tali da registrare impulsi molto brevi inferiori a 100 ps.
Le applicazioni sono da trovare nel campo delle macchine acceleratrici e di diagnostica digitale
Fast Capacitve Probe for Electromagnetic pulses diagnostic
No full textGeneration of electromagnetic pulses of fast and high intensity is constantly in progress. The real time diagnostic of short current or voltage pulses is essential for good application with sophisticate and modern devices. Streak camera systems are able to detect sub ps pulses of particle or X-ray beams, but losing the possibility to use the beams during the detection. Besides, real time measurements of electromagnetic pulses offer a better control of the device functioning. Nowadays fast current or voltage pulses of sub ten picoseconds can be recorded in real time by means of modern fast digitizing oscilloscopes, but to get good results it is necessary to realize fast probes. Fast capacitive probes, which we will present in this work, are simple capacitors conceived like a transmission line. For this reason it is indispensable to construct them with electrodes of suitable dimensions and forms, e.g., i: the probe has to got a folded central electrode in order to present the internal skin dimensions close to external ones, ii: it has to got a particular configuration able to contain and to shield the integrating resistor avoiding electromagnetic irradiations. Such a probe is suitable for measuring fast voltage and current pulses propagating in coaxial structures of known characteristic impedance. Analysing the behaviour of the probe in a 50 Ω coaxial structure, the voltage amplification resulted to be of (3.6±0.1)x10-4 and as a consequence the current attenuation factor of 56±1 A/V. The rise time response was very interesting. It was less than 320 ps, which was limited by oscilloscope bandwave. In vacuum electrical devices the capacitor probe can measure potential values of the order of 100 kV
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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