Effect of Process Parameters on Laser Powder Bed Fusion of Al-Sn Miscibility Gap Alloy

Al-Sn binary system is a miscibility gap alloy consisting of an Al-rich phase and a Sn-rich phase. This system is traditionally applied in bearings and more recently found application as form-stable phase change material (PCM) exploiting solid-liquid phase transition of Sn. A careful choice of production process is required to avoid macro-segregation of the two phases, which have different densities and melting temperatures. In the present study, the additive manufacturing process known as laser powder bed fusion (LPBF) was applied to an Al-Sn alloy with 20% volume of Sn, as a rapid solidification process. The effect of process parameters on microstructure and hardness was evaluated. Moreover, feasibility and stability with thermal cycles of a lattice structure of the same alloy were experimentally investigated. An Al-Sn lattice structure could be used as container for a lower melting organic PCM (e.g., a paraffin or a fatty acid), providing high thermal diffusivity thanks to the metallic network and a "safety system" reducing thermal diffusivity if the system temperature overcomes Sn melting temperature. Even if focused on Al-Sn to be applied in thermal management systems, the study offers a contribution in view of the optimization of manufacturing processes locally involving high solidification rates and reheat cycles in other miscibility gap alloys (e.g., Fe-Cu) with similar thermal or structural applications

Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells

Essential oils from various aromatic plants have been reported to exert chemopreventive and/or antitumor effects. In addition, a number of studies have shown the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to conventional anticancer drugs. The success of chemotherapeutic agents is often hindered by the development of drug resistance, with multidrug resistant (MDR) phenotypes reported in a number of tumors, generally involving reduced intracellular drug accumulation due to increased drug efflux by membrane transporters. In the present study, the effects of linalool (LIN), a monoterpene alcohol found in the essential oils from many aromatic plants, on the growth of two human breast adenocarcinoma cell lines, MCF7 WT and multidrug resistant MCF7 AdrR, were investigated, both as a single agent and in combination with doxorubicin (DOX). The results reported here show that LIN only moderately inhibits cell proliferation; interestingly, however, subtoxic concentrations of LIN potentiate DOX-induced cytotoxicity and pro-apoptotic effects in both cell lines. A significant synergism can be observed in MCF7 AdrR cells, which may be due, at least in part, to the ability of LIN to increase DOX accumulation and to induce a decrease in Bcl-xL levels. In summary, the results of the present study suggest that LIN may improve the therapeutic index of anthracyclines in the management of breast cancer, especially in MDR tumors

Characterisation of the Thermal Damage in a Martensitic Steel Substrate Consequent to Laser Cladding Process

n/

Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple-negative) breast cancer cells

BACKGROUND: Metastatic triple-negative breast cancer is mostly incurable, due to lack of suitable drug targets. The insulin-like growth factor (IGF) system could provide such a target, and IGF-1 receptor (IGF-1R)-directed agents are already available, but seem unable to control all the complexities of the system, including crosstalk with hypoxia-inducible pathways. METHODS: Migration of triple-negative MDA-231 breast cancer cells and its modulation by IGFs, the IGF-1R inhibitor NVP-AEW541 and the IGF-2-sequestering monoclonal antibody MAB292 were assessed by the scratch wound healing and Boyden chamber assays; the effect of topotecan (inhibiting hypoxia-inducible factor-1 (HIF-1)) under hypoxia was also evaluated. Constitutive as well as drug-modulated levels of components of the IGF and HIF-1 pathways were evaluated by western blotting and qPCR. RESULTS: IGF-induced migration of MDA-231 cells was not abrogated by the IGF-1R inhibitor NVP-AEW541, whereas IGF-2 sequestration by MAB292 significantly reduced cell migration. Under hypoxia, topotecan was also effective, likely by reducing HIF-1-induced IGF-2 release. Simultaneous targeting of IGF-1R and IGF-2 or HIF-1 completely abolished cell migration. CONCLUSIONS: IR activation may account for the failure of NVP-AEW541 to suppress MDA-231 cell migration. Ligand-targeting compounds, or co-inhibition of the IGF and HIF-1 systems, may prevent activation of compensatory signalling, thereby providing a valuable addition to IGF-1R inhibitor-based therapies

PROPOSAL OF A CLASSIFICATION OF DEFECTS OF HIGH-PRESSURE DIECAST PRODUCTS

The paper gives an introduction to the one of the current actions of the WG “Quality of High Pressure DieCast (HPDC) products” within the TC “High pressure diecasting” of the Italian Association of Metallurgy, The preparation and dissemination of common tools to allow foundries to define a proper, comparable, quality standard is in fact one of the current targets of this WG. The basic tool, to which this paper refers, is a common terminology and classification of defects of HPDC products. An initial survey of literature and industrially adopted classifications of defect in components cast in metallic dies, revealed that the geometry and origin-based approaches are often mixed giving rise to a wide range of hybrid classifications. The proposed classification of defects of HPDC products, discussed within the WG with the contribution of several foundries, is a multi-level, hybrid-type classification. In the first level defects are grouped on the basis of their position (surface/internal and geometry defects) according to the typical control operations during which they can be detected and to the effects of defects on the functionality of the parts. The second level of the classification groups defect in classes according to their general metallurgical origin. The proposed classification doss not specify defect/cause correlations, but gives starting points to the identification of their specific causes. In order to better specify these features the analogies between the origin of internal/surface defects are highlighted by corresponding names for Level II classes: gas-related, shrinkagerelated, filling-related, thermal contraction defects and undesired phases. In addition the class of metal/die interaction defects is proposed for surface defects. The specific defects identified are those included in the third level of the classification. In the present paper an introduction to the general classes of defects defined in Level II is proposed. The action of the WG concerning defect classification of HPDC parts will be completed with the compilation of the official document including the proposed classification and multi-language terminology equivalences

Proteomic analysis of dopamine and \u3b1-synuclein interplay in a cellular model of Parkinson's disease pathogenesis

Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson\u2019s disease. a-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased a-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing a-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate a-synuclein expression. However, the effect is not observed in cells that already overexpress a-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with a-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, a-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment.Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson's disease. \u3b1-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased \u3b1-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing \u3b1-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate \u3b1-synuclein expression. However, the effect is not observed in cells that already overexpress \u3b1-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with \u3b1-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, \u3b1-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment. \ua9 2010 The Authors Journal compilation \ua9 2010 FEBS

Critical assessment of thermal conductivity models for Miscibility Gap Alloy-based composite Phase Change Materials for high temperature Thermal Energy Storage

Miscibility Gap Alloys (MGAs), such as Al-Sn-based systems, provide a viable solution for the development of composite Phase Change Materials (PCMs) for Thermal Energy Storage (TES) purposes. Their successful production depends on the cooling rate imposed to the melt. Finite Element Analyses (FEA), which relies also on thermal conductivity values, represent a powerful tool for the design of the production process. Thermal conductivity, which depends on the arrangement of the phases in the system, also affects the thermal response of the alloy. In the view of evaluating the impact of the phase morphology, the authors adapted some of the models developed for composites and solutions to Al-Sn and Al-Sn-Si-Mg alloys, characterized by broad solidification ranges in terms of composition and temperature and by significantly different phases thermal conductivity. In the fully-liquid range, Filippov and Novoselova model was selected for the description of both alloys. Models that consider sphere-like dispersions give values quite close to the theoretical upper Wiener bound when the high-melting phase is solid. The phase morphology impact is relevant when the solidification range is considered. The resulting arrangement-related thermal conductivity curves are compared to those supplied by CALPHAD-based software and to available literature data