Geomorphological map of the Lipari volcanic island (Aeolian Archipelago – Italy)

A 1:10,000-scale geomorphological map of the Lipari volcanic island (Aeolian Archipelago – Italy) is presented in this paper. The associated map, which includes volcanic and epivolcanic landforms, is obtained combining the available geological information with data derived from the analysis of a digital terrain model, integrated with aerial photographic observations and field surveys. The map shows that the location of the main volcanic morphologies is strongly controlled by local tectonic structures striking NNW-SSE, while the epivolcanic morphologies are mainly related to the continuous uplift induced by the prevalence of regional tectonic processes. The aim of this work is to provide an improved geomorphological map, with a reasonably comprehensive overview of the landforms present in the most densely populated island of the Aeolian Archipelago. This map can be also used as a support for future studies of land management on the island

Targeted sequencing of BRAF by MinION in archival Formalin-Fixed Paraffin-Embedded specimens allows to discriminate between Hairy Cell Leukemia and Hair Cell Leukemia Variant

Targeted sequencing of BRAF by MinION in archival Formalin-Fixed Paraffin-Embedded specimens allows to discriminate between Hairy Cell Leukemia and Hair Cell Leukemia Varian

Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities

JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino acid sequences of JMJD6 necessary for the interaction with Coll-I are part of the conformational epitope recognized by P4E11. In mice injected with mouse 4T1 breast carcinoma cells, treatment with P4E11 reduced fibrosis at the primary tumor and prevented lung metastases. Reduction of fibrosis has also been documented in human breast and ovarian tumors (MDA-MB-231 and IGROV1, respectively) xenotransplanted into immunodeficient mice treated with P4E11. In summary, this study uncovers a new localization and function for JMJD6 that is most likely independent from its canonical enzymatic activities, and demonstrates that JMJD6 can functionally interact with Coll-I. P4E11 mAb, inhibiting JMJD6/Coll-I interaction, represents a new opportunity to target fibrotic and tumor diseases

Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment

The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases in C57BL/6 mice. Aerosolization of CpG-ODN with Poly(I:C) into the bronchoalveolar space reduced the presence of M2-associated arginase- and IL-10-secreting macrophages in tumor-bearing lungs and increased the antitumor activity of aerosolized CpG-ODN alone against B16 lung metastases without apparent signs of toxicity or injury of the bronchial-bronchiolar structures and alveolar walls. Moreover, CpG-ODN/Poly(I:C) aerosol combined with dacarbazine, a therapeutic agent used in patients with inoperable metastatic melanoma able to exert immunostimulatory effects, led to a significant increase in antitumor activity as compared to treatments with aerosolized CpG-ODN/Poly(I:C) or dacarbazine alone. This effect was related to an enhanced recruitment and cytotoxic activity of tumor-infiltrating NK cells in the lung. Our results point to aerosol delivery as a convenient approach for repeated applications of immunostimulants in patients with lung metastases to maintain a continuous local activation of innate immune cells while suppressing polarization of tumor-infiltrating macrophages to an M2 phenotype

Prime stime mediante simulazioni numeriche delle velocita' di lancio di ejecta allo stromboli e valutazioni sul rischio vulcanico indotto

The typical strombolian activity of Stromboli volcano ranges from a nearly continuous venting of ash and gases (normal strombolian activity) to moderate, up to violent explosive pulses (violent strombolian activity). Moreover, both regimes are sometimes punctuated without warning by phases of scaled up, distinct and more energetic huge bursts separated by time intervals ranging from minutes to hours (paroxysmal activity). As this eruptive style causes the blasting from the summit vents of hot fragments of new lava and blocks with different velocities, densities and impact sites, the main volcanic risk at Stromboli is related to the hazard due to ballistic showers of these ejecta on the built-up areas of the island (Stromboli and Ginostra villages). For that reason i) a land use map of the island has been produced and ii) a number of numerical simulations of ballistic trajectories for to constrain the velocity ranges of the three different explosive regimes has been performed with the "Eject!" software (L.G. Mastin, 2001) by using the average density of dense blocks (2800 kg/m3) and juvenile bombs (1970 kg/m3) from a set of 44 ejecta that we collected on the flanks of the volcano. The reliable ranges of initial velocity at the takeoff point (summit vents) that we obtained are: 40 m/s ÷ 60 m/s for normal strombolian activity, 70 m/s ÷ 100 m/s for violent strombolian activity and 120 m/s ÷ 200 m/s for paroxysmal strombolian activity. Without wind, the cross-correlation of the land use - velocity data indicates that both for the villages of Stromboli and Ginostra an ejecta impact probability is realistic only in paroxysmal activity periods, while it’s definitively absent during normal and violent strombolian regimes. Following tail-winds = 25 m/s simulations (wind velocity sometimes observed at the Stromboli island), the resulting hazard increases with respect to the tail-winds = 0 m/s simulations for both Stromboli and Ginostra during the paroxysmal regime, and become appreciable for the Ginostra village even during violent strombolian activity

Verifying the reliability of historical sources through an archaeometric study

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Conceptual Design of the Steam Generators for the EU DEMO WCLL Reactor

In the framework of the EUROfusion Horizon Europe Programme, ENEA and its linked third parties are in charge of the conceptual design of the steam generators belonging to EU DEMO WCLL Breeding Blanket Primary Heat Transfer Systems (BB PHTSs). In particular, in 2021, design activities and supporting numerical simulations were carried out in order to achieve a feasible and robust preliminary concept design of the Once Through Steam Generators (OTSGs), selected as reference technology for the DEMO Balance of Plant at the end of the Horizon 2020 Programme. The design of these components is very challenging. In fact, the steam generators have to deliver the thermal power removed from the two principal blanket subsystems, i.e., the First Wall (FW) and the Breeding Zone (BZ), to the Power Conversion System (PCS) for its conversion into electricity, operating under plasma pulsed regime and staying in dwell period at a very low power level (decay power). Consequently, the OTSG stability and control represent a key point for these systems' operability and the success of a DEMO BoP configuration with direct coupling between the BB PHTS and the PCS. In this paper, the authors reported and critically discussed the FW and BZ steam generators' thermal-hydraulic and mechanical design, the developed 3D CAD models, as well as the main results of the stability analyses and the control strategy to be adopted

Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling

Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation. NET fostered the progression of the indolent NPM1-driven myeloproliferation toward an exacerbated and proliferative dysplastic phenotype. Enrichment in NET structures was found in the bone marrow of patients with autoimmune disorders and in NPM1-mutated acute myelogenous leukemia (AML) patients. Genes involved in NET formation in the animal model were used to design a NET-related inflammatory gene signature for human myeloid malignancies. This signature identified two AML subsets with different genetic complexity and different enrichment in NPM1 mutation and predicted the response to immunomodulatory drugs. Our results indicate that stromal/ECM changes and priming of bone marrow NETosis by systemic inflammatory conditions can complement genetic and epigenetic events towards the development and progression of myeloid malignancy

Controversies in ACL revision surgery: Italian expert group consensus and state of the art

Background Revision ACL reconstruction is a complex topic with many controversies and not-easy-to-make decisions. The authors' aim is to provide some feasible advice that can be applied in daily clinical practice with the goal of facilitating the decision-making process and improving the outcomes of patients subjected to revision ACL reconstruction. Methods A national survey with seven questions about the most controversial topics in revision ACL reconstruction was emailed to members of two societies: SIOT and SIAGASCOT. The participants' answers were collected, the most recent literature was analyzed, and a consensus was created by the authors, according to their long-term surgical experience. Conclusions The decision-making process in revision ACL reconstruction starts with a standardized imaging protocol (weight-bearing radiographs, CT scan, and MRI). One-stage surgery is indicated in almost all cases (exceptions are severe tunnel enlargement and infection), while the choice of graft depends on the previously used graft and the dimensions of the tunnels, with better clinical outcomes obtained for autografts. Additional procedures such as lateral extra-articular tenodesis in high-grade pivot-shift knees, biplanar HTO in the case of severe coronal malalignment, and meniscal suture improve the clinical outcome and should be considered case by case