Numerical Analysis for Reduced-scale Road Tunnel Model Equipped with Axial Jet Fan Ventilation System☆

Abstract In this paper a preliminary tridimensional CFD analysis is carried out for a future realization of a reduced-scale road tunnel experimental apparatus of 1/50 equipped with different impulsive fans, traditional and alternative. The alternative jet fan is provided of inlet/outlet sections inclined at a fixed pitch angle (α=6°) toward the tunnel floor. Typically, in the experimental scale tunnel model the air flow induced by ventilation system is provided by an external fan and fully developed flow field is considered. In this paper, the authors have simulated a realistic full and reduced-scale tunnel in order to evaluate the influence of ceiling and floor roughness height on the velocity field to identify an appropriate material for a future experimental apparatus. The jet fans are simulated as a simple momentum source. The fan is considered to be infinitely thin and the discontinuous pressure rise (pressure drop) across it is defined as a function of the air velocity through the fan. In order to create a reduced-scale model from a full scale, Froude method is applied to preserve geometrical, kinematical and dynamical similitude. The results, provided in terms of axial velocity profiles in different tunnel sections, show the overlapping between velocity profiles of full scale numerical model with those of the reduced-scale model, for the both ventilation systems

Employment of Oligodeoxynucleotide plus Interleukin-2 Improves Cytogenetic Analysis in Splenic Marginal Zone Lymphoma

To compare the efficiency of novel mitogenic agents and traditional mitosis inductors, 18 patients with splenic marginal zone lymphoma (SMZL) were studied. Three cultures using oligodeoxynucleotide (ODN) plus interleukin-2 (IL-2), or TPA, or LPS were setup in each patient. Seventeen/18 cases with ODN + IL2 had moderate/good proliferation (94, 4%) as compared with 10/18 cases with TPA and LPS (55%) (P = .015); 14/18 (77, 7%) cases with ODN + IL2 had sufficient good quality of banding as compared with 8/18 cases (44, 4%) with TPA and LPS. The karyotype could be defined from ODN + IL2-stimulated cultures in all 18 patients, 14 of whom (77, 7%) had a cytogenetic aberration, whereas clonal aberrations could be documented in 9 and in 3 cases by stimulation with LPS and TPA, respectively. Recurrent chromosome aberrations in our series were represented by aberrations of chromosome 14q in 5 patients, by trisomy 12 and 7q deletion in 4 cases each, and by abnormalities involving 11q and 13q in two cases each. These findings show that stimulation with ODN + IL2 offers more mitotic figures of better quality and results in an increased rate of clonal aberrations in SMZL, making this method ideal for prospective studies aiming at the definition of the prognostic impact of cytogenetic aberrations in this disorder

Epha3 acts as proangiogenic factor in multiple myeloma

This study investigates the role of ephrin receptor A3 (EphA3) in the angiogenesis of Multiple Myeloma (MM) and the effects of a selective target of EphA3 by a specific monoclonal antibody on primary bone marrow endothelial cells (ECs) of MM patients.EphA3 mRNA and protein were evaluated in ECs of MM patients (MMECs), in ECs of patients with monoclonal gammopathies of undetermined significance (MGECs) and in ECs of healthy subjects (control ECs). The effects of EphA3 targeting by mRNA silencing (siRNA) or by the anti EphA3 antibody on the angiogenesis were evaluated. We found that EphA3 is highly expressed in MMECs compared to the other EC types. Loss of function of EphA3 by siRNA significantly inhibited the ability of MMECs to adhere to fibronectin, to migrate and to form tube like structures in vitro, without affecting cell proliferation or viability. In addition, gene expression profiling showed that knockdown of EphA3 down modulated some molecules that regulate adhesion, migration and invasion processes. Interestingly, EphA3 targeting by an anti EphA3 antibody reduced all the MMEC angiogenesis-related functions in vitro. In conclusion, our findings suggest that EphA3 plays an important role in MM angiogenesis

A Pyrazolo[3,4-d]pyrimidine compound inhibits Fyn phosphorylation and induces apoptosis in natural killer cell leukemia

Natural killer (NK) cell neoplasms are characterized by clonal proliferation of cytotoxic NK cells. Since there is no standard treatment to date, new therapeutic options are needed, especially for NK aggressive tumors. Fyn tyrosine kinase has a key role in different biological processes, such as cell growth and differentiation, being also involved in the pathogenesis of hematologic malignancies. Our previous studies led us to identify 4c pyrazolo[3,4-d]pyrimidine compound capable of inhibiting Fyn activation and inducing apoptosis in different cancer cell lines. Here we investigated the presence of Fyn and the effect of its inhibitor in NK malignant cells. Firstly, we showed Fyn over-expression in NK leukemic cells compared to peripheral blood mononuclear cells from healthy donors. Subsequently, we demonstrated that 4c treatment reduced cell viability, induced caspase 3-mediate apoptosis and cell cycle arrest in NK cells. Moreover, by inhibiting Fyn phosphorylation, 4c compound reduced Akt and P70 S6 kinase activation and changed the expression of genes involved in cell death and survival in NK cells. Our study demonstrated that Fyn is involved in the pathogenesis of NK leukemia and that it could represent a potential target for this neoplasm. Moreover, we proved that Fyn inhibitor pyrazolo[3,4-d]pyrimidine compound, could be a started point to develop new therapeutic agents

SARS-CoV-2 Infection Incidence and Outcome Before and After Full Vaccination in Patients With Monoclonal Gammopathy of Undetermined Significance

N

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies

none20: Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).noneMina, Roberto; Bonello, Francesca; Petrucci, Maria Teresa; Liberati, Anna Marina; Conticello, Concetta; Ballanti, Stelvio; Musto, Pellegrino; Olivieri, Attilio; Benevolo, Giulia; Capra, Andrea; Gilestro, Milena; Galieni, Piero; Cavo, Michele; Siniscalchi, Agostina; Palumbo, Antonio; Montefusco, Vittorio; Gaidano, Gianluca; Omedé, Paola; Boccadoro, Mario; Bringhen, SaraMina, Roberto; Bonello, Francesca; Petrucci, Maria Teresa; Liberati, Anna Marina; Conticello, Concetta; Ballanti, Stelvio; Musto, Pellegrino; Olivieri, Attilio; Benevolo, Giulia; Capra, Andrea; Gilestro, Milena; Galieni, Piero; Cavo, Michele; Siniscalchi, Agostina; Palumbo, Antonio; Montefusco, Vittorio; Gaidano, Gianluca; Omedé, Paola; Boccadoro, Mario; Bringhen, Sar