ORCID Profile
0000-0001-5637-8983
Current Organisations
Institute of Oncology Research
,
University of Portsmouth
,
Istituto Oncologico della Svizzera Italiana
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Publisher: Rockefeller University Press
Date: 13-06-2011
DOI: 10.1084/JEM.20110921
Abstract: The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown. The full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains & clonally represented gene alterations/case, including predominantly nonsilent mutations, and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. Although most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%), as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.
Publisher: Elsevier BV
Date: 2022
Publisher: MDPI AG
Date: 11-07-2021
DOI: 10.3390/MET11071103
Abstract: The integrity of machined holes depends on many parameters, some of which are related to the cutting tool (geometry, coating, material). Other influential parameters are related to the machining process variables (spindle speed, feed rate, workpiece material), all of which can affect the quality of the hole and drilling induced damage on its surface. This study investigates the effect of uncoated tools and four types of tool coatings (TiN-, TiCN-, TiAlN-, and TiSiN) on the hole quality and its microstructure. The study analyzed several hole geometrical metrics, namely hole size, circularity, cylindricity, and perpendicularity of an Al2024 aluminum alloy using a multi-spindle drilling process that utilizes three drills capable of creating multiple holes simultaneously. The results showed that the uncoated carbide drill gave a high-hole quality at low spindle speed. Regarding the coated drills, TiCN coated drills produced holes with the least deviation, circularity, cylindricity and perpendicularity at high spindle speeds. TiSiN–carbide coated drills produced the most oversized holes and noticeable damage and deformations on their surface following TiAlN and TiN. The common surface damage found on the inner hole surface was smearing, feed marks, and metal debris adhesion. The ANOVA results revealed that the tool type had the highest percentage contribution that mainly affected the hole quality.
Publisher: Springer Science and Business Media LLC
Date: 15-06-2010
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: MDPI AG
Date: 09-07-2023
Abstract: This paper deals with an experimental investigation of hole quality in Al2024-T3, which is one of the aerospace alloys used in aircraft fuselage skin due to its high level of resistance to fatigue crack propagation. The experiments are conducted with 6 mm uncoated carbide and HSS drill bits using a CNC machine under dry conditions and different drilling parameters. The characteristics of the hole quality are investigated in terms of its perpendicularity, cylindricity, circularity and hole size. An ANOVA (analysis of variance) and Pareto charts are used to analyze the effects of the drilling parameters on the hole quality. The hole quality is also assessed using a digital microscope to observe the formation of hole burrs. Moreover, scanning electron microscopy is also used to investigate the inside-hole surface defects. Further investigations are carried out using optical microscopy to inspect the post-drilling tool condition at high drilling parameters. The results show that hole quality reduces as the feed rate and spindle speed increase. However, from the ANOVA results and Pareto charts, the influence of the feed rate on the hole quality is found to be insignificant. At the same time, the type of drill bit material shows the highest percentage of contribution affecting the hole quality, following the spindle speed. The HSS drill bit shows more adhesion and built-up edges than the uncoated carbide drill bit. There were more burrs formed at the hole edges when the holes were drilled with uncoated HSS drill bits. In the same way, the SEM analysis reveals more surface deformation and damage defects inside the hole walls of holes drilled using the uncoated HSS drill bit.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2009
Publisher: The American Association of Immunologists
Date: 15-12-2005
DOI: 10.4049/JIMMUNOL.175.12.7837
Abstract: We used a comprehensive collection of Affymetrix microarray datasets to ascertain which genes or molecules distinguish the known major subsets of human T cells. Our strategy allowed us to identify the genes expressed in most T cell subsets: TCR αβ+ and γδ+, three effector subsets (Th1, Th2, and T follicular helper cells), T central memory, T effector memory, activated T cells, and others. Our genechip dataset also allowed for identification of genes preferentially or exclusively expressed by T cells, compared with numerous non-T cell leukocyte subsets profiled. Cross-comparisons between microarray datasets revealed important features of certain subsets. For instance, blood γδ T cells expressed no unique gene transcripts, but did differ from αβ T cells in numerous genes that were down-regulated. Hierarchical clustering of all the genes differentially expressed between T cell subsets enabled the identification of precise signatures. Moreover, the different T cell subsets could be distinguished at the level of gene expression by a smaller subset of predictor genes, most of which have not previously been associated directly with any of the in idual subsets. T cell activation had the greatest influence on gene regulation, whereas central and effector memory T cells displayed surprisingly similar gene expression profiles. Knowledge of the patterns of gene expression that underlie fundamental T cell activities, such as activation, various effector functions, and immunological memory, provide the basis for a better understanding of T cells and their role in immune defense.
Publisher: Elsevier BV
Date: 05-2008
Abstract: Non-Hodgkin's lymphomas constitute one half of malignancies arising in the orbit and the ocular adnexae. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histological category in this anatomic region. The incidence of ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) is increasing and recent studies offered new relevant insights in molecular, pathogenetic and therapeutic issues on these neoplasms. A pathogenetic model of antigen-driven lymphoproliferation similar to that reported for Helicobacter pylori-related gastric MALT lymphomas has been hypothesized for OAML. This notion is supported by the association between OAML and Chlamydophila psittaci infection, an association that is of likely pathogenetic relevance and may influence both the biological behavior and the therapeutic management of these neoplasms. However, this association displays evident geographical variability indicating that other etiopathogenic agents could be involved. These recent acquisitions coupled with the occurrence of chromosomal translocations and other genetic alterations, as well as additional risk factors like autoimmune disorders have contributed to render OAML an exciting challenge for a broad group of physicians and scientists. OAML is an indolent and rarely lethal malignancy that, in selected patients, can be managed with observation alone. Lymphomatous lesions are frequently responsible for symptoms affecting patient's quality of life, requiring, therefore, immediate treatment. Several therapeutic strategies are available, often associated with relevant side-effects. However, the therapeutic choice in OAML is not supported by consolidated evidence due to the lack of prospective trials. In this review, we analyze the most relevant biological, molecular, pathological and clinical features of OAML and propose some therapeutic guidelines for patients affected by this malignancy.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-08-2012
Abstract: The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL. Forty-seven patients were registered. Tumor tissue, conjunctival swabs, and peripheral blood from 44 patients were assessed for seven Chlamydiaceae infections by three polymerase chain reaction protocols. Thirty-four patients with measurable or parametrable disease were treated with doxycycline and assessed for chlamydial eradication and lymphoma response (primary end point). Cp DNA was detected in biopsies of 39 patients (89%) no other Chlamydiaceae were detected. Twenty-nine patients had Cp DNA in baseline swabs and/or blood s les and were evaluable for chlamydial eradication, which was achieved in 14 patients (48%). Lymphoma regression was complete in six patients and partial in 16 (overall response rate, 65% 95% CI, 49% to 81%) 11 had stable disease, and one had progressive disease. At a median follow-up of 37 months (range, 15 to 62 months), 20 patients remained relapse free (5-year progression-free survival [PFS] ± standard deviation, 55% ± 9%). Cp eradication was associated with improved response rate (86% v 47% P = .02) and 5-year PFS (68% v 47% P = .11). Upfront doxycycline is a rational and active treatment for patients with stage I Cp-positive OAMZL. Lymphoma regression is consequent to Cp eradication, which can easily be monitored on conjunctival and blood s les. Prospective trials aimed at identifying more effective administration schedules for doxycycline are warranted.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Francesco Bertoni.