Search

Supplementary Figure S1: Analysis of the mutational burden in sarcoma patients.Supplementary Figure S2: Characterization of 2c-induced cell death in LMS cells. Supplementary Figure S3: Dose dependent studies. Supplementary Figure S4: Sub-mitochondrial localization of the ATP-synthase-β subunit, Cytochrome c and DIABLO/SMAC. Supplementary Figure S5: STED super-resolution microscopy of mitochondria under 2c-induced proteotoxic stress. Supplementary Figure S6: Sub-mitochondrial localization of the ATP-synthase-β subunit, Cytochrome c and DIABLO/SMAC in LMS cells. Supplementary Figure S7: HSF1 expression in LMS cells. Supplementary Table S1: List of genes constituting the two 2c-signatures used in this study. Supplementary Table S2:The 2c proteotoxic stress signature

Mitochondrial dynamics in untreated SK-UT-1 cells

Leiomyosarcomas are rare and aggressive tumors characterized by a complex karyotype. Surgical resection with or without radiotherapy and chemotherapy is the standard curative treatment. Unfortunately, a high percentage of leiomyosarcomas recurs and metastasizes. In these cases, doxorubicin and ifosfamide represent the standard treatment but with low response rates. Here, we evaluated the induction of proteotoxic stress as a possible strategy to kill leiomyosarcoma cells in a therapeutic perspective. We show that aggressive leiomyosarcomas coexist with high levels of proteotoxic stress. As a consequence, we hypothesized that leiomyosarcoma cells are vulnerable to further increases of proteotoxic stress. The small compound 2c is a strong inducer of proteotoxic stress. In leiomyosarcoma cells, it triggers cell death coupled to a profound reorganization of the mitochondrial network. By using stimulated emission depletion microscopy, we have unveiled the existence of DIABLO/SMAC clusters that are modulated by 2c. Finally, we have engineered a new version of 2c linked to polyethylene glycol though a short peptide, named 2cPP. This new prodrug is specifically activated by proteases present in the tumor microenvironment. 2cPP shows a strong antitumor activity in vivo against leiomyosarcomas and no toxicity against normal cells.

Additive Manufacturing (AM) technologies are recognized as the future of the manufacturing industry thanks to their possibilities in terms of shape design, part functionality, and material efficiency. The use of AM technologies in many industrial sectors is growing, also due to the increasing knowledge regarding the AM processes and the characteristics of the final part. One of the most promising AM techniques is the Directed Energy Deposition (DED) that uses a thermal source to generate a melt pool on a substrate into which metal powder is injected. The potentialities of DED technology are the ability to process large build volumes (> 1000 mm in size), the ability to deliver the material directly into the melt pool, the possibility to repair existing parts, and the opportunity to change the material during the building process, thus creating functionally graded material. In this paper, a review of the industrial applications of Laser Powder Directed Energy Deposition (LP-DED) is presented. Three main applications are identified in repairing, designed material, and production. Despite the enormous advantages of LP-DED, from the literature, it emerges that the most relevant application refers to the repairing process of high-value components.

A low-profile single-ridge waveguide magic-T is proposed as a combination of two T-junctions at an X band. A slot coupling technique is used to reduce the component dimensions in the E-plane, thus leading to a low profile. The device can assume two configurations by arranging the sum and difference ports in the same or opposite direction, an attractive feature in the design of beamforming networks with complex routing. A magic-T prototype is fabricated using laser powder bed fusion additive manufacturing techniques. Good agreement between simulations and measurements is found.

(1) Background: To assess the clinical safety and efficacy of a new piezoelectric instrument for orthodontic clean-up; (2) Methods: An in-vitro comparative study on 75 teeth extracted for orthodontic reasons compared the tested method (Treatment 1) with two other procedures: One step finisher and polisher (Inverted cone One gloss Shofu Dental, Kyoto, Japan) (Treatment 2) and twelve-fluted tungsten carbide bur (123-603-00, Dentaurum, Pforzheim, Germany) and Sof-Lex discs Pop-On XT Kit (3M ESPE) (Treatment 3), with n:25 samples in each group. Clinical safety (enamel volume loss) and effectiveness (residual adhesive volume) were assessed using the structured light 3D scanner Atos Compact Scan (GOM GmbH) together with the support of Atos Professional software. The surfaces were scanned three times to assess: (i) the volume of the residual adhesive (RAV) after bracket removal; (ii) the volume of the relative residual adhesive (dAV) after the clean-up procedure; (iii) volume of the enamel loss (EVL); (3) Results: The mean RAV (mm3) was 0.239 ± 0.337; 0.069 ± 0.124, 0.120 ± 0.193 and the mean EVL (mm3) was 0.1870 ± 0.177, 0.187 ± 0.299 and 0.290 ± 0.205, for treatment 1, 2 and 3, respectively. The distribution was asymmetrical between groups in both cases; (4) Conclusions: The tested instrument proved to be effective and safe for post-orthodontic clean-up. With the increasing use of invisible aligners, the possibility of using an ergonomic and fast instrument is of benefit to both patient and practitioner.

Over the last decade, the enormous potential of metal additive manufacturing (AM) processes has led these technologies to establish their position in many industries. Much effort is being made toward their widespread application; however, much remains to be done to achieve full industrialization of these processes. Therefore, many companies, research centers and universities are investing in comprehensive research and development activities in order to further promote the industrialization of metal AM. This review traces the progress of metal AM technologies through an investigation of patents. In the present study, beam-based metal AM patents were searched through the Orbit Intelligence database. First, the number of patents per year was studied, indicating that, as expected, there is strong growth in AM patenting activities. The patents were afterward examined in order to highlight the key players in the field, and it was found that the main players investing in this market are: multidisciplinary companies, AM machine producers, end users working, especially in the aerospace sector, universities and research centers. The patents were then analyzed to understand the technology domains covered by each key player and their trend of investments. Finally, the patents in the field of Materials and Metallurgy were studied individually to identify the main topics faced by the most used alloy classes: Al-, Ni- and Ti-based alloys and steels. The extensive study of these patents clearly indicated that the main gaps to fill in metal AM are strongly material dependent and that it is possible to find correlations between the alloy classes, their main industrial applications and their specific AM processability issues. The current study provides insights into global trends that can help industrial markets to identify the right investment direction and research to identify topics for future investigation.

Fast progress in near-net-shape production of parts has attracted vast interest in internal surface finishing. Interest in designing a modern finishing machine to cover the different shapes of workpieces with different materials has risen recently, and the current state of technology cannot satisfy the high requirements for finishing internal channels in metal-additive-manufactured parts. Therefore, in this work, an effort has been made to close the current gaps. This literature review aims to trace the development of different non-traditional internal surface finishing methods. For this reason, attention is focused on the working principles, capabilities, and limitations of the most applicable processes, such as internal magnetic abrasive finishing, abrasive flow machining, fluidized bed machining, cavitation abrasive finishing, and electrochemical machining. Thereafter, a comparison is presented based on which models were surveyed in detail, with particular attention to their specifications and methods. The assessment is measured by seven key features, with two selected methods deciding their value for a proper hybrid machine.

Laser Powder-based Directed Energy Deposition (LP-DED) process is a cutting-edge Additive Manufacturing (AM) technology for metal part repair and production. The disruptive potentialities of LP-DED are nowadays limited by the difficulty in the identification of the optimized set of process parameters, typically obtained from long and expensive experimental trials. In this work, a thermal simulation tool able to predict material deposition behaviour is developed using a finite element code. An original method is defined to model the material addition and energy flow. The forecasting capabilities of the model in terms of penetration depth and track dimensions are evaluated by comparing the numerical outcomes with experimental data.

Additive manufacturing (AM) technology has great potential in manufacturing complex internal channels for several applications such as satellite communication systems, electronics and gas turbine airfoils. These applications can have complex shape and make traditional finishing processes a challenge for additive parts. Therefore, it is desirable that the internal surfaces be as close as possible to the tolerance of the field of application. In this study, a complex component was designed and manufactured in AlSi10Mg alloy through laser powder bed fusion (L-PBF) process. Using the data from the 3D scans, internal surface roughness and deviations from the CAD model were calculated.

Stereolithography is known as one of the best Additive Manufacturing technologies in terms of geometrical and dimensional precision for polymeric materials. In recent years, a lot of studies have shown that the creation of ceramic resins, through a particular combination of monomeric components and ceramic powders, allows to obtain complex shape geometries thanks to the photopolymerization process. This review highlights the characteristics and properties of ceramic resins, peculiarities of the ceramic stereolithography processes, up to the relationship between the composition of the ceramic resin and the complexity of the post-processing phases. The comparison of different studies allows outlining the most common steps for the production of ceramic resins, as well as the physical and chemical compatibility of the different compounds that must be studied for the good feasibility of the process.

Tin-bronze alloys with a tin content of at least 10 wt% have excellent mechanical properties, wear resistance, and corrosion resistance. Among these alloys, Cu-10Sn was investigated in this study for production with the laser powder bed fusion process with a 500W Yb:YAG laser. In particular, a design of experiment (DoE) was developed in order to identify the optimal process parameters to obtain full density, low surface roughness, and high dimensional accuracy. Samples were characterized with Archimedes’ method and optical microscopy to determine their final density. It was shown that the first method is fast but not as reliable as the second one. A first mechanical characterization was performed through microhardness tests. Finally, a set of process parameters was identified to produce fully dense samples with low surface roughness and high accuracy. The results showed that the volumetric energy density could represent an approach that is too simplified, therefore limiting the direct correlation with the physical aspects of the process.

Traditional sintering processes are carried out to achieve complete material densification. In an electron beam powder bed fusion (EB-PBF) process, the same sintering mechanisms occur but only with the aim to form small connections between the particles (necks). A proper neck formation is central for the EB-PBF process because, among other effects, ensures the thermal stability of the process and helps to avoid smoke phenomena. This work presents a numerical study of neck formation under the EB-PBF processing conditions. A new type of modelling is introduced for the temperature sintering load and included in a phase-field model, which simulates the neck growth during the EB-PBF process of Ti6Al4V powders. The model was validated with an ad-hoc experiment, which provided a deviation with respect to the estimated neck diameter of about 9%. The deviation was investigated by reasonably varying the processing conditions. The results showed that the thermal history, the process time scale (including also the cooling phase), and the geometrical characteristics of the particles significantly affected the sintering rate and neck radius.

3D printing has been widely adopted not only by individuals or people printing in the community, such as the Markers’ movement but also by industries from different sectors. Unlike traditional manufacturing technologies, layer-wise manufacturing enables live monitoring of the process and part quality layer after layer through proper sensors installed in the working volume of the 3d printing system. Therefore, from the sustainability perspective, unnecessary waste of material and energy can be avoided by aborting the fabrication when a serious defect is detected in one or more layers. In this paper, a low-cost camera and computer vision algorithms are used for the implementation of an in-situ monitoring system for open 3D printing. After printing each layer, the step of image capture is introduced by modification of the open ISO G-code file. The image of the single part layer is then compared to the information extracted from the G-code for automatic detection of manufacturing defects. The area of missing or exceeding material is computed and shown to the user, which can decide to cancel the job in case of important flaws to avoid any unnecessary waste in terms of material, time and costs.

Lattice structures are 3D open topologically ordered geometries that repeat an elementary cell in a predefined 3D space. Struts connected in specific nodes define the cell. Lattice structures are typical geometries that represent the design freedom unlocked by additive manufacturing (AM) and are unachievable with traditional processes. By tuning the morphometric parameters of the cell, its mechanical response can be significantly altered. Because of that, an accurate understanding of the process capabilities is crucial for achieving the nominally designed properties. Considering an electron beam powder bed fusion process, in this work, the same nominal lattice structure is produced under different processing conditions to determine the relationship between the process parameters, the actual cell morphometric parameters, and its mechanical response. Strut dimension, relative density and cross-section are measured using advanced X-ray computed tomography scanning analyses. Uniaxial compressive tests describe the mechanical performance. Inferential and descriptive statistical analyses are applied to investigate the effect of process parameters on the actual strut dimension and infer regression models. The results show that even slight variations of the process parameters significantly affect the morphometric structure parameters that result deviated from the nominal ones. The work demonstrates a strong correlation between all morphometric structure parameters and corresponding mechanical properties. The obtained regression model can predict the strut dimension from the process parameters, which can be then used to estimate the actual relative density and strut size. With this control and without any complex design procedure, a fine-tuning of process parameters allows a precise 3D spatial and localised control of structure properties to produce functionalised structures directly.

Additive manufacturing (AM) is a disruptive technology as it pushes the frontier of manufacturing towards a new design perspective, such as the ability to shape geometries that cannot be formed with any other traditional technique. AM has today shown successful applications in several fields such as the biomedical sector in which it provides a relatively fast and effective way to solve even complex medical cases. From this point of view, the purpose of this paper is to illustrate AM technologies currently used in the medical field and their benefits along with contemporary. The review highlights differences in processes, materials, and design of additive manufacturing techniques used in biomedical applications. Successful case studies are presented to emphasise the potentiality of AM processes. The presented review supports improvements in materials and design for future researches in biomedical surgeries using instruments and implants made by AM.