Core Binding Factor Leukemia : Chromatin Remodeling Moves Towards Oncogenic Transcription

Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBF\u3b2-SMMHC) translocation product respectively, disrupt the essential hematopoietic function of the CBF. In the past decade, remarkable progress has been achieved in understanding the structure, three-dimensional (3D) chromosomal topology, and disease-inducing genetic and epigenetic abnormalities of the fusion proteins that arise from disruption of the CBF subunit alpha and beta genes. Although CBFLs have a relatively good prognosis compared to other leukemia subtypes, 40-50% of patients still relapse, requiring intensive chemotherapy and allogenic hematopoietic cell transplantation (alloHCT). To provide a rationale for the CBFL-associated altered hematopoietic development, in this review, we summarize the current understanding on the various molecular mechanisms, including dysregulation of Wnt/\u3b2-catenin signaling as an early event that triggers the translocations, playing a pivotal role in the pathophysiology of CBFL. Translation of these findings into the clinical setting is just beginning by improvement in risk stratification, MRD assessment, and development of targeted therapies

Saggio di commento all'Assioco pseudoplatonico

Nell'introduzione sono presentate le testimonianze antiche e bizantine sul dialogo; successivamente sono discusse le posizioni assunte dalla critica negli ultimi due secoli in merito alle questioni di attribuzione e datazione; infine è tracciato un breve profilo della letteratura consolatoria al fine di mostrare le peculiarità con cui il dialogo si inserisce nel genere. Segue un commento lemmatico continuo sulla prima parte del dialogo, scandita in quattro sezioni (364a1-65a2; 365a2-65c9; 365c10-66b2; 366b3-67a2); sono presi in esame problemi di natura linguistica, di critica testuale, storico-filosofici, letterari e più generalmente esegetici

A reproducible approach with R markdown to automatic classification of medical certificates in French

In this paper, we report the ongoing developments of our first participation to the Cross-Language Evaluation Forum (CLEF) eHealth Task 1: “Multilingual Information Extraction - ICD10 coding” (Névéol et al., 2017). The task consists in labelling death certificates, in French with international standard codes. In particular, we wanted to accomplish the goal of the ‘Replication track’ of this Task which promotes the sharing of tools and the dissemination of solid, reproducible results.In questo articolo presentiamo gli sviluppi del lavoro iniziato con la partecipazione al Laboratorio CrossLanguage Evaluation Forum (CLEF) eHealth denominato: “Multilingual Information Extraction - ICD10 coding” (Névéol et al., 2017) che ha come obiettivo quello di classificare certificati di morte in lingua francese con dei codici standard internazionali. In particolare, abbiamo come obiettivo quello proposto dalla ‘Replication track’ di questo Task, che promuove la condivisione di strumenti e la diffusione di risultati riproducibili

Volcanological implications inferred from chemical analyses of olivines collected at São Jorge Island (Azorean Archipelago, Portugal)

openThe Azorean Archipelago, situated in the North Atlantic Ocean, is composed of nine active volcanic islands, put in place during the Quaternary. They are a result of the interaction between the Azores hotspot and the Mid-Atlantic Ridge (MAR). The archipelago intersects the MAR, with the Western Islands situated on the ridge's western flanks, and the Central and Eastern Islands located at the east of it. This intricate setting is situated at the triple junction of the North American, Eurasian, and Nubian plates. In addition, the Terceira Rift, an exceptionally slow-spreading plate boundary, influence the archipelago's tectonics and seismicity. The Azorean plateau experiences active faults contributing to high-magnitude earthquakes, along with secondary manifestations of volcanism like fumaroles and thermal springs. Together with Madeira, the Canary Islands, and Cape Verde, the Azores constitute the Macaronesian island group. These islands are volcanic systems that result from mantle plume activity, featuring the characteristic composition of Ocean Island Basalt (OIB) magma. This study focuses on olivine phenocrysts from the Holocene Manadas Volcanic Complex basalts on São Jorge Island, Central Azores. These crystals provide insights into magma evolution and diffusion processes. Olivine, that is commonly found in effusive alkaline mafic volcanic rocks, reacts when the magma composition changes, developing chemical zoning. Examining this zoning, both with optical mineralogy techniques and with electron microprobe analyses, made it possible to reveal the evolution of magmatic reservoirs and conduits of this volcanic complex. In addition, chemical profiles of olivine crystals and chemical diffusion modelling were used to calculate an approximate time scale of the magma evolution and eruption. We found distinct cases of both close and open-system differentiation, like magma mixing, which occurred either well before or immediately preceding eruptions. Overall, the study improves the understanding of the complex geological processes shaping the Azores and contributes to the wider field of volcanic and magmatic studies.The Azorean Archipelago, situated in the North Atlantic Ocean, is composed of nine active volcanic islands, put in place during the Quaternary. They are a result of the interaction between the Azores hotspot and the Mid-Atlantic Ridge (MAR). The archipelago intersects the MAR, with the Western Islands situated on the ridge's western flanks, and the Central and Eastern Islands located at the east of it. This intricate setting is situated at the triple junction of the North American, Eurasian, and Nubian plates. In addition, the Terceira Rift, an exceptionally slow-spreading plate boundary, influence the archipelago's tectonics and seismicity. The Azorean plateau experiences active faults contributing to high-magnitude earthquakes, along with secondary manifestations of volcanism like fumaroles and thermal springs. Together with Madeira, the Canary Islands, and Cape Verde, the Azores constitute the Macaronesian island group. These islands are volcanic systems that result from mantle plume activity, featuring the characteristic composition of Ocean Island Basalt (OIB) magma. This study focuses on olivine phenocrysts from the Holocene Manadas Volcanic Complex basalts on São Jorge Island, Central Azores. These crystals provide insights into magma evolution and diffusion processes. Olivine, that is commonly found in effusive alkaline mafic volcanic rocks, reacts when the magma composition changes, developing chemical zoning. Examining this zoning, both with optical mineralogy techniques and with electron microprobe analyses, made it possible to reveal the evolution of magmatic reservoirs and conduits of this volcanic complex. In addition, chemical profiles of olivine crystals and chemical diffusion modelling were used to calculate an approximate time scale of the magma evolution and eruption. We found distinct cases of both close and open-system differentiation, like magma mixing, which occurred either well before or immediately preceding eruptions. Overall, the study improves the understanding of the complex geological processes shaping the Azores and contributes to the wider field of volcanic and magmatic studies

A lexicon based approach to classification of ICD10 codes. IMS unipd at CLEF eHealth task 1

International audienc

An interactive two-dimensional approach to query aspects rewriting in systematic reviews. IMS unipd at CLEF eHealth task 2

International audienc

'Res corporales' and 'res incorporales'. Roman Foundation and Current Development of a Bipartition

The article aims to critically reconstruct the dichotomy 'res corporales'-'res incorporales' from Gai 2.12-14. In particular, attention is focused on the historical origin of the distinction and the discretional criterion underlying it, on the comparison between this distinction and the further distinction relative to 'res mancipi'-'res nec mancipi', and, finally, on the developments that the conceptual pair finds in the main modern codifications

Evaluation of the stress–strain curve of metallic materials by spherical indentation

AbstractA method for deducing the stress–strain uniaxial properties of metallic materials from instrumented spherical indentation is presented along with an experimental verification.An extensive finite element parametric analysis of the spherical indentation was performed in order to generate a database of load vs. depth of penetration curves for classes of materials selected in order to represent the metals commonly employed in structural applications. The stress–strain curves of the materials were represented with three parameters: the Young modulus for the elastic regime, the stress of proportionality limit and the strain-hardening coefficient for the elastic–plastic regime.The indentation curves simulated by the finite element analyses were fitted in order to obtain a continuous function which can produce accurate load vs. depth curves for any combination of the constitutive elastic–plastic parameters. On the basis of this continuous function, an optimization algorithm was then employed to deduce the material elastic–plastic parameters and the related stress–strain curve when the measured load vs. depth curve is available by an instrumented spherical indentation test.The proposed method was verified by comparing the predicted stress–strain curves with those directly measured for several metallic alloys having different mechanical properties.This result confirms the possibility to deduce the complete stress–strain curve of a metal alloy with good accuracy by a properly conducted instrumented spherical indentation test and a suitable interpretation technique of the measured quantities

Surface and subsurface rolling contact fatigue characteristic depths and proposal of stress indexes

The rolling contact fatigue is distinguished into subsurface initiated (spalling and case crushing) and surface initiated (pitting and micropitting). A characteristic depth was identified for each of these mechanism. The characteristic depth of the case crushing is the hardening depth, while for the spalling it is the maximum cyclic shear stress depth. The pitting depth is the size of the crack for which the mode I stress intensity factor range, due to the fluid pressurization, is higher than the threshold. This depth can be similar to the micropitting depth, in the order of 10 µm, for heavily loaded small radius contacts. Rolling contact fatigue cyclic shear stress indexes are then defined on the basis of the characteristic depths, and they identify the load intensity of each rolling contact fatigue mechanism. The characteristic depths and the stress index approach can be used to relate specific tests to component design, without any size effect misinterpretation