Search results for: Annamaria Aloisio

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

Abstract:

ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

Procedia PDF Downloads 109

Authors: Angelo Aloisio Dag, Pasquale Pasca, Massimo Fragiacomo, Ferdinando Totani, Gianfranco Totani

Abstract:

The estimate of the velocity of shear waves (Vs) is essential in seismic engineering to characterize the dynamic response of soils. There are various direct methods to estimate the Vs. The authors report the results of site characterization in Macerata, where they measured the Vs using the seismic dilatometer in a 100m deep borehole. The standard Vs estimation originates from the cross-correlation between the signals acquired by two geophones at increasing depths. This paper focuses on the estimate of the dependence of Vs on the wavenumber. The dispersion curves reveal an unexpected hyperbolic dispersion curve typical of Lamb waves. Interestingly, the contribution of Lamb waves may be notable up to 100m depth. The amplitude of surface waves decrease rapidly with depth: still, their influence may be essential up to depths considered unusual for standard geotechnical investigations, where their effect is generally neglected. Accordingly, these waves may bias the outcomes of the standard Vs estimations, which ignore frequency-dependent phenomena. The paper proposes an enhancement of the accepted procedure to estimate Vs and addresses the importance of Lamb waves in soil characterization.

Keywords: dispersion curve, seismic dilatometer, shear wave, soil mechanics

Procedia PDF Downloads 172

Authors: Rafael Santos Fischer, Aloísio Leoni Schmid, Amanda Dalla-Bonna

Abstract:

The life cycle analysis and the energy life cycle analysis are useful design support tools when sustainability becomes imperative. The final phase of buildings life cycle is probably the least known, on which less knowledge is available. In the Brazilian building industry, the lifespan of a building design rarely is treated as a definite design parameter. There is rather a common sense attitude to take any building demands as permanent, and to take for granted that buildings solutions are durable and solid. Housing, being a permanent issue in any society, presents a real challenge to the choice of a design lifespan. In Brazilian history, there was a contrast of the native solutions of collective, non-durable houses built by several nomadic tribes, and the stone and masonry buildings introduced by the sedentary Portuguese conquerors. Durable buildings are commonly associated with welfare. However, social dynamics makes traditional families of both parents and children be just one of several possible arrangements. In addition, a more liberal attitude towards family leads to an increase in the number of people living in alternative arrangements. Japan is an example of country where houses have been made intentionally ephemeral since the half of 20th century. The present article presents the development of a flexible housing design solution on the basis of the Design Science Research approach. A comparison in terms of energy life cycle shows how flexibility and dematerialization may point at a feasible future for housing policies in Brazil.

Keywords: adaptability, adaptable building, embodied energy, life cyclce analysis, social housing

Procedia PDF Downloads 589

Authors: Annamária Käferné Rácz, Bence Jáger, Balázs Kövesdi, László Dunai

Abstract:

Due to the numerous advantages of steel corrugated web girders, its application field is growing for bridges as well as for buildings. The global stability behavior of such girders is significantly larger than those of conventional I-girders with flat web, thus the application of the structural steel material can be significantly reduced. Design codes and specifications do not provide clear and complete rules or recommendations for the determination of the lateral torsional buckling (LTB) resistance of corrugated web girders. Therefore, the authors made a thorough investigation regarding the LTB resistance of the corrugated web girders. Finite element (FE) simulations have been performed to develop new design formulas for the determination of the LTB resistance of trapezoidally corrugated web girders. FE model is developed considering geometrical and material nonlinear analysis using equivalent geometric imperfections (GMNI analysis). The equivalent geometric imperfections involve the initial geometric imperfections and residual stresses coming from rolling, welding and flame cutting. Imperfection sensitivity analysis was performed to determine the necessary magnitudes regarding only the first eigenmodes shape imperfections. By the help of the validated FE model, an extended parametric study is carried out to investigate the LTB resistance for different trapezoidal corrugation profiles. First, the critical moment of a specific girder was calculated by FE model. The critical moments from the FE calculations are compared to the previous analytical calculation proposals. Then, nonlinear analysis was carried out to determine the ultimate resistance. Due to the numerical investigations, new proposals are developed for the determination of the LTB resistance of trapezoidally corrugated web girders through a modification factor on the design method related to the conventional flat web girders.

Keywords: corrugated web, lateral torsional buckling, critical moment, FE modeling

Procedia PDF Downloads 282