Phenomenological aspects of quasi-perfect pivots in metallic pantographic structures

This article discusses the results of the first attempts to print metal pantographic structures with perfect pivots, i.e. with rotational hinges connecting the two families of fibers composing the network without any stiffness. On the one hand, it is observed that perfect pivots do not behave as expected theoretically. On the other hand, the force measured during a bias extension test is a few orders of magnitude lower than that measured for pantographic structures with standard pivots (where a certain stiffness is associated to the interconnecting hinges). This leads to considering the pivots as quasi-perfect (non-zero stiffness, but neither the theoretical one which can be computed by means of the geometrical features of the pivot). Numerical simulations complete the analysis by showing how, by modulating the torsional stiffness of the pivots, it is possible to reproduce the force-displacement plot both in the case of standard pivots and with quasi-perfect ones

Thermal analysis of parts produced by L-PBF and correlation with dimensional accuracy

Laser-Power Bed Fusion (L-PBF) is continuing to grow in use among the industrial field. This process allows the manufacturing of parts with complex geometry, good dimensional accuracy, and few post-processing steps. However, deviations can still be observed on the final parts. It is known in the literature that all of these deviations can be imputed to some extent to thermal phenomena such as overheating or thermal gradient through residual stress relaxation. The objective of this study is to reach a better understanding of the influence of the thermal properties on the dimensional accuracy of parts produced by L-PBF. To do so, an infrared camera has been instrumented inside the machine, allowing the determination of the temperature of parts during the process. Thin walls with different process parameters (laser power, scanning speed…) and nominal dimensions were manufactured and measured afterwards with a coordinate measuring machine (CMM). Thermal acquisitions were performed at different moments during the fabrication and give access to the cooling rate of the observed parts. Least square fitting has been used to approximate the cooling rate function and returns characteristic times that are used to compare the different manufacturing configurations. In the end, a correlation has been established between the process parameters, the thermal parameters, and the dimensional accuracy of the parts. Form deviations, possibly due to residual stress, have only been observed on the thinnest wall, which is also the part with the highest measured thermal gradients. Other form deviations were due to roughness

Optimization and comparison of porosity rate measurement methods of Selective Laser Melted metallic parts

The systematic occurrence of porosities inside selective laser melted (SLM) parts is a well-known phenomenon. In order to improve the density of SLM parts, it is important not only to assess the physical origin of the different types of porosities, but also to be able to measure as precisely as possible the porosity rate so that one may select the optimum manufacturing parameters. Considering 316 L steel parts built with different input energies, the current paper aims to (1) present the different types of porosities generated by SLM and their origins, (2) compare different methods for measuring parts density and (3) propose optimal procedures. After a preliminary optimization step, three methods were used for quantifying porosity rate: the Archimedes method, the helium pycnometry and micrographic observations. The Archimedes method shows that results depend on the nature and temperature of the fluid, but also on the sample volume and its surface roughness. During the micrographic observations, it has been shown that the results depend on the magnification used and the number of micrographs considered. A comparison of the three methods showed that the optimized Archimedes method and the helium pycnometry technique gave similar results, whereas optimized micrographic observations systematically underestimated the porosity rate. In a second step, samples were analyzed to illustrate the physical phenomena involved in the generation of porosities. It was confirmed that: (1) low Volume Energy Density (VED) causes non-spherical porosities due to insufficient fusion, (2) in intermediary VED the small amount of remaining blowhole porosities come from gas occlusion in the melt-pool and (3) in excessive VED, cavities are formed due to the key-hole welding mode

When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2 with Its Partner DUOXA2

Aims: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown. The contribution of some cysteine residues located in the N-terminal ectodomain of DUOX2 in a surface protein?protein interaction is suggested. We have investigated the involvement of different cysteine residues in the formation of covalent bonds that could be of critical importance for the function of the complex. Results: We report the identification and the characterization of an intramolecular disulfide bond between cys-124 of the N-terminal ectodomain and cys-1162 of an extracellular loop of DUOX2, which has important functional implications in both export and activity of DUOX2. This intramolecular bridge provides structural support for the formation of interdisulfide bridges between the N-terminal domain of DUOX2 and the two extracellular loops of its partner, DUOXA2. Innovation: Both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like function with respect to its partner. Conclusions: The oxidative folding of DUOX2 that takes place in the endoplasmic reticulum (ER) appears to be a key event in the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate conformation of the N-terminal region, which is propitious to subsequent covalent interactions with the maturation factor, DUOXA2. Antioxid. Redox Signal. 23, 724?733.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140308/1/ars.2015.6265.pd

Redox modifications of cysteine-containing proteins, cell cycle arrest and translation inhibition: Involvement in vitamin C-induced breast cancer cell death

International audienceVitamin C (VitC) possesses pro-oxidant properties at high pharmacologic concentrations which favor re-purposing VitC as an anti-cancer therapeutic agent. However, redox-based anticancer properties of VitC are yet partially understood. We examined the difference between the reduced and oxidized forms of VitC, ascorbic acid (AA) and dehydroascorbic acid (DHA), in terms of cytotoxicity and redox mechanisms toward breast cancer cells. Our data showed that AA displayed higher cytotoxicity towards triple-negative breast cancer (TNBC) cell lines in vitro than DHA. AA exhibited a similar cytotoxicity on non-TNBC cells, while only a minor detrimental effect on noncancerous cells. Using MDA-MB-231, a representative TNBC cell line, we observed that AA-and DHA-induced cytotoxicity were linked to cellular redox-state alterations. Hydrogen peroxide (H 2 O 2) accumulation in the extracellular medium and in different intracellular compartments, and to a lesser degree, intracellular glu-tathione oxidation, played a key role in AA-induced cytotoxicity. In contrast, DHA affected glutathione oxidation and had less cytotoxicity. A "redoxome" approach revealed that AA treatment altered the redox state of key antioxidants and a number of cysteine-containing proteins including many nucleic acid binding proteins and proteins involved in RNA and DNA metabolisms and in energetic processes. We showed that cell cycle arrest and translation inhibition were associated with AA-induced cytotoxicity. Finally, bioinformatics analysis and biological experiments identified that peroxiredoxin 1 (PRDX1) expression levels correlated with AA differential cytotoxicity in breast cancer cells, suggesting a potential predictive value of PRDX1. This study provides insight into the redox-based mechanisms of VitC anticancer activity, indicating that pharmacologic doses of VitC and VitC-based rational drug combinations could be novel therapeutic opportunities for triple-negative breast cancer

Pantographic metamaterials: A view towards applications

The purpose of this article is to show the basic characteristics of the so-called pantographic metamaterial. Here we underline how the microstructure provides some exotic properties and, in principle, implies the second gradient nature of this type of metamaterial. Thanks to the development of additive manufacturing technology (especially in the field of metallurgy) we are now able to produce real samples and carry out experimental measurements to validate the proposed models. In this article we show some new experimental tests, obtained by considering pantographic structures printed in stainless steel. Numerical simulations are briefly shown to show the validity of the theoretical model developed to describe the pantographic metamaterial

The macroscopic behavior of pantographic sheets depends mainly on their microstructure: experimental evidence and qualitative analysis of damage in metallic specimens

Recently the exotic properties of pantographic metamaterials have been investigated, and various mathematical models (both discrete and continuous) have been introduced. However, the experimental evidence available up to now concerns only polyamide specimens. In this paper, we use specimens printed using metallic powder. We prove experimentally that the main qualitative and quantitative features of pantographic sheets in planar deformation are independent of the constituting materials, at least when they can be regarded as homogeneous and isotropic at micro-level. Of course, the absolute value of Young’s modulus of constituent material affects the overall reaction force needed to the hard device to impose a given displacement: A first investigation on this effect is also attempted

BRAFV600E hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality. Objective: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries regarding the prevalence of BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E oncogene in Moroccan thyroid carcinomas. Methods: In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Military Hospital of Instruction Mohammed V \u2018HMIMV\u2019 in Rabat, we report, using direct genomic sequencing, the assessment of BRAFV600E in 37 thyroid tumors. Results: We detected BRAFV600E mutation exclusively in Papillary Thyroid Carcinomas \u2018PTC\u2019 with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas \u2019PTC\u2019 is more frequent than Follicular Thyroid Carcinomas \u2018FTC\u2019 and Anaplastic Thyroid Carcinomas \u2018ATC\u2019 (29 PTC, 7 FTC and 1 ATC). Conclusion: Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide geographic regions

Tumor-Associated Macrophages (TAMs) Form an Interconnected Cellular Supportive Network in Anaplastic Thyroid Carcinoma

BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined