Technological Feasibility of Lattice Materials by Laser-Based Powder Bed Fusion of A357.0

Lattice materials represent one of the utmost applications of additive manufacturing. The promising synergy between additive processes and topology optimization finds full development in achieving components that comprise bulky and hollow areas, as well as intermediate zones. Yet, the potential to design innovative shapes can be hindered by technological limits. The article tackles the manufacturability by laser-based powder bed fusion (L-PBF) of aluminum-based lattice materials by varying the beam diameter and thus the relative density. The printing accuracy is evaluated against the distinctive building phenomena in L-PBF of metals. The main finding consists in identification of a feasibility window that can be used for development of lightweight industrial components. A relative density of 20% compared with fully solid material (aluminum alloy A357.0) is found as the lowest boundary for a 3-mm cell dimension for a body-centered cubic structure with struts along the cube edges (BCCXYZ) and built with the vertical edges parallel to the growth direction to account for the worst-case scenario. Lighter structures of this kind, even if theoretically compliant with technical specifications of the machine, result in unstable frameworks

Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer

Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH. Release of miR-424 in small EVs was enhanced in cell lines (LNCaPabl), transgenic mice (Pb-Cre4;Ptenflox/flox;Rosa26ERG/ERG) and patient-derived xenograft (PDX) models of aggressive disease. EVs containing miR-424 promoted stem-like traits and tumor-initiating properties in normal prostate epithelial cells while enhanced tumorigenesis in transformed prostate epithelial cells. Intravenous administration of miR-424 positive EVs to mice, mimicking blood circulation, promoted miR-424 transfer and tumor growth in xenograft models. Circulating miR-424 positive EVs from patients with aggressive primary and metastatic tumors induced stem-like features when supplemented to prostate epithelial cells. This study establishes that EVs-mediated transfer of miR-424 across heterogeneous cell populations is an important mechanism of tumor self-sustenance, disease recurrence and progression. These findings might indicate novel approaches for the management and therapy of prostate cancer

Advanced high performance vehicle frame design by means of topology optimization

Automotive chassis design, often based on the company know-how and the designer experience, usually leads to consolidated solutions that are poorly innovative and not necessarily altogether efficient. Optimization techniques are powerful means for systematic design that can make it possible to avoid this drawback. The present study proposes a methodology for automotive chassis design based on topology, topometry and size optimizations coupled with fem analyses. In particular, the methodology is applied to the design of a chassis suitable for a rear-central engine high performance car. A massive 3d fem model is conceived, in order to respect the geometrical requirements yet leaving maximum freedom to the topology optimization algorithm. Shell mod- els are employed for the subsequent topometry and size optimizations. The objective is the minimization of the chassis mass in fulfillment of a given set of structural performance constraints. The results demonstrate the general applicability of the method proposed

Advanced high performance vehicle frame design by means of topology optimization

Automotive chassis design, often based on the company know-how and the designer experience, usually leads to consolidated solutions that are poorly innovative and not necessarily altogether efficient. Optimization techniques are powerful means for systematic design that can make it possible to avoid this drawback. The present study proposes a methodology for automotive chassis design based on topology, topometry and size optimizations coupled with fem analyses. In particular, the methodology is applied to the design of a chassis suitable for a rear-central engine high performance car. A massive 3d fem model is conceived, in order to respect the geometrical requirements yet leaving maximum freedom to the topology optimization algorithm. Shell mod- els are employed for the subsequent topometry and size optimizations. The objective is the minimization of the chassis mass in fulfillment of a given set of structural performance constraints. The results demonstrate the general applicability of the method proposed

Mechanistic Modeling of Genetic Circuits for ArsR Arsenic Regulation.

Bioreporters are living cells that generate an easily measurable signal in the presence of a chemical compound. They acquire their functionality from synthetic gene circuits, the configuration of which defines the response signal and signal-to-noise ratio. Bioreporters based on the Escherichia coli ArsR system have raised significant interest for quantifying arsenic pollution, but they need to be carefully optimized to accurately work in the required low concentration range (1-10 μg arsenite L-1). To better understand the general functioning of ArsR-based genetic circuits, we developed a comprehensive mechanistic model that was empirically tested and validated in E. coli carrying different circuit configurations. The model accounts for the different elements in the circuits (proteins, DNA, chemical species), and their detailed affinities and interactions, and predicts the (fluorescent) output from the bioreporter cell as a function of arsenite concentration. The model was parametrized using existing ArsR biochemical data, and then complemented by parameter estimations from the accompanying experimental data using a scatter search algorithm. Model predictions and experimental data were largely coherent for feedback and uncoupled circuit configurations, different ArsR alleles, promoter strengths, and presence or absence of arsenic efflux in the bioreporters. Interestingly, the model predicted a particular useful circuit variant having steeper response at low arsenite concentrations, which was experimentally confirmed and may be useful as arsenic bioreporter in the field. From the extensive validation we expect the mechanistic model to further be a useful framework for detailed modeling of other synthetic circuits

Weight reduction by topology optimization of an engine subframe mount, designed for additive manufacturing production

Additive Manufacturing (AM) technologies are getting more and more strategic for different purposes in many industrial fields. Among the most outstanding are part prototyping, single part to small batch production, relatively reduced manufacturing times and investments costs, reduced material consumption, and innovative and efficient shapes. The considerable advantages these technologies offer, compared to subtractive ones, make additive manufacturing a potentially industry-leading process in almost all domains - from aeronautics to the medical industry. Under these circumstances, the inspiration given by topology optimization tools can lead to feasible industrial parts, with fewer constraints in comparison to traditional manufacturing processes. The paper presents the development and the results obtained using topology optimization and design for AM technology on an automotive part: an engine mount sub-frame component for a rear middle engine sports car. The final design enables a significant weight reduction