Lattice and trabecular structures are excellent candidates for energy absorbing applications such as personal protective equipment or any sort of bumper. Additive manufacturing technologies allow ...more freedom in the design of new topologies such as trabecular and lattice structures overcoming the limitation of the traditional manufacturing processes. In the present research, an investigation on the ductile behaviour of additive structures is presented. In a first phase, a series of 18-Ni300 steel specimens with different geometries has been printed using the SLM (Selective Laser Melting) technology. Experimental quasi-static tests on those samples were numerically reproduced, in order to retrieve the actual stress state, quantify the plastic strain at failure and calibrate a ductile damage model. In a second phase, trabecular structures, made of the same material and processed with the same technology as the samples, were produced and experimentally tested in a compression test. Simulations including the calibrated model were used to reproduce the response of the elementary trabecular cell subjected to different loading conditions (micro-scale simulations). This kind of simulations is very time-consuming and not suitable for the design/optimisation of large structures made by thousands of elementary cells. To overcome this limitation, in a third phase of the project, an effective and efficient design methodology has been implemented. Each elementary cell is modelled as an equivalent non-linear three-dimensional spring. The force-displacement (torque-rotation) relations in different directions were obtained with the previously described micro-scale FE simulations. In this manner, the computational costs can be reduced by many orders of magnitude allowing the study of complex real systems.
Low-velocity impacts represent a major concern for aeronautical structures, sometimes producing barely detectable damage that could severely hamper the aircraft safety, even with regards to metallic ...structures. For this reason, the development of an automated impact monitoring system is desired. From a passive monitoring perspective, any impact generates a strain wave that can be acquired using sensor networks; signal processing techniques allow for extracting features useful for impact identification, possibly in an automatic way. However, impact wave characteristics are related to the impactor stiffness; this presents a problem for the evaluation of an impact-related feature and for the development of an automatic approach to impact identification. This work discusses the problem of reducing the influence of the impactor stiffness on one of the features typically characterizing the impact event, i.e., the time of arrival (TOA). Two passive sensor networks composed of accelerometers and piezoelectric sensors are installed on two metallic specimens, consisting of an aluminum skin and a sandwich panel, with aluminum skins and NOMEX
honeycomb core. The effect of different impactor stiffnesses is investigated by resorting to an impact hammer, equipped with different tips. Subsequently, a method for data processing is defined to obtain a feature insensitive to the impactor stiffness, and this method is applied to multiple impact signals for feature uncertainty evaluation.
Nucleophosmin (
) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented
mutations in ...around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with
-mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing
-mutated MNs with blast count <20%, since
-mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to
-mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether
mutations may become sufficient to diagnose AML, irrespective of blast percentage.
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired ...driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.
Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and ...smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.
Both human immunodeficiency virus (HIV) infection and acute myeloid leukemia (AML) may be considered relatively uncommon disorders in the general population, but the precise incidence of AML in ...people living with HIV infection (PLWH) is uncertain. However, life expectancy of newly infected HIV-positive patients receiving anti-retroviral therapy (ART) is gradually increasing, rivaling that of age-matched HIV-negative individuals, so that the occurrence of AML is also expected to progressively increase. Even if HIV is not reported to be directly mutagenic, several indirect leukemogenic mechanisms, mainly based on bone marrow microenvironment disruption, have been proposed. Despite a well-controlled HIV infection under ART should no longer be considered per se a contraindication to intensive chemotherapeutic approaches, including allogeneic hematopoietic stem cell transplantation, in selected fit patients with AML, survival outcomes are still generally unsatisfactory. We discussed several controversial issues about pathogenesis and clinical management of AML in PLWH, but few evidence-based answers may currently be provided, due to the limited number of cases reported in the literature, mainly as case reports or small retrospective case series. Prospective multicenter clinical trials are warranted to more precisely investigate epidemiology and cytogenetic/molecular features of AML in PLWH, but also to standardize and further improve its therapeutic management.
The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute ...myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.
Nowadays the design of large-scale structures can be effectively improved by the adoption of numerical models. Even if experimental tests still play a fundamental role, a methodological approach that ...combines experimental testing and modelling technique can significantly improve the understanding of the matter. This, in fact, would result in a more reliable optimization process, drastically reducing efforts and uncertainties towards the implementation of the final product. The present work deals with the development of a finite element model for the analysis of a full-scale prototype of an innovative parabolic trough collector. The collector is analysed under several load conditions in order to evaluate its structural behaviour. Each load configuration is also numerically reproduced. Moreover, it is demonstrated that the model is capable of reproducing both the global (stiffness) and local (strain state) behaviour of the structure. Specifically, the comparison between experimental data and numerical results show a good agreement for the global parameter torsional stiffness. Local strain values are also well reproduced in high-stressed zone. Thus, the model can be used as a reliable “virtual tool” for designers to evaluate the suitability of layout modifications, thereby replacing and reducing the amount of commonly needed experimental tests and, consequently, reducing time and costs. Finally, an example of the potentiality of the finite element model adopted for a computer-aided engineering approach is shown to determine the most promising solution for increasing the torsional stiffness of the trough, while simultaneously limiting the required experimental tests.
A novel fiber optic sensing technology for high frequency dynamics detection is proposed in this paper, specifically tailored for structural health monitoring applications based on strain wave ...analysis, for both passive impact identification and active Lamb wave monitoring. The sensing solution relies on a fiber optic-based interferometric architecture associated to an innovative coherent detection scheme, which retrieves in a completely passive way the high-frequency phase information of the received optical signal. The sensing fiber can be arranged into different layouts, depending on the requirement of the specific application, in order to enhance the sensor sensitivity while still ensuring a limited gauge length if punctual measures are required. For active Lamb wave monitoring, this results in a sensing fiber arranged in multiple loops glued on an aluminum thin panel in order to increase the phase signal only in correspondence to the sensing points of interest. Instead, for passive impact identification, the required sensitivity is guaranteed by simply exploiting a longer gauge length glued to the structure. The fiber optic coherent (FOC) sensor is exploited to detect the strain waves emitted by a piezoelectric transducer placed on the aluminum panel or generated by an impulse hammer, respectively. The FOC sensor measurements have been compared with both a numerical model based on Finite Elements and traditional piezoelectric sensors, confirming a good agreement between experimental and simulated results for both active and passive impact monitoring scenarios.
In the present work an experimental program aimed at assessing the mechanical behavior of an innovative parabolic solar trough is presented. More specifically, a lightweight and low-cost collector ...making large use of adhesive joints, which can be easily assembled on-site, still performing at a high efficiency, was designed. Static and fatigue tests were performed on a full-scale prototype of the collector in the pre-production stage. The tests included differential torsion, concentrated and distributed bending, and distributed load (wind effect). During the tests, a network of strain gauges was placed in the most critical locations to measure the strain field, while laser sensors and cable transducers were placed in strategic positions to measure the displacements. The results demonstrate the strengths of the innovative parabolic trough collector and support the assessment of its structural integrity.
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