Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1β, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.     

Efficient Geodesic Attribute Thinnings Based on the Barycentric Diameter

An attribute opening is an idempotent, anti-extensive and increasing operator, which removes from an image connected components which do not fulfil a given criterion. When the increasingness property is dropped, we obtain a—more general—attribute thinning. In this paper, we propose efficient grey scale thinnings based on geodesic attributes. Given that the geodesic diameter is time consuming, we propose a new geodesic attribute, the barycentric diameter to speed up the computation time. Then, we give the theoretical error bound between these two attributes, and we note that in practice, the barycentric diameter gives very similar results in comparison with the geodesic diameter. Finally, we present the algorithm with further optimisations, to obtain a 60× speed up. We illustrate the use of these thinnings in automated non-destructive material inspection: the detection of cracks. We discuss the advantages of these operators over other methods such as path openings or the supremum of openings with segments.     

Fretting wear behavior of bulk amorphous steel

Fretting wear of Fe₄₁Co₇Cr₁₅Mo₁₄C₁₅B₆Y₂ bulk metallic glass (BMG) was investigated using the ball-on-disc measurement. The wear behaviors of the samples roughly follow the classical Archard wear law at room temperature. The influence of temperature on wear resistance (R_w) and microhardness (H_v) was evaluated. A good linear correlation was found between R_w and H for the Fe-based BMG. The results indicate that the hardness softening is responsible for the decrease of R_w at high temperature. The wear mechanism at high temperature was elucidated through the analysis of oxidation and debris morphology on the wear scar. Compared with traditional crystalline steels and other non-ferrous metal-based glassy alloys, the bulk amorphous steel shows higher wear resistance and hardness, which promotes its application as an advanced engineering material.     

Micro-scale energy dissipation mechanisms during dynamic fracture in natural polyphase ceramic blocks

The dynamic fracture of natural polyphase ceramic (granite) blocks by high-speed impact at 207 m/s, 420 m/s and 537 m/s has been investigated. An electromagnetic railgun was used as the launch system. Results reveal that the number of fragments increases substantially, and the dominant length scale in their probability distributions decreases, as the impact energy is increased. Micro-scale studies of the fracture surfaces reveals evidence of localized temperatures in excess of 2000 K brought on by frictional melting via fracturing and slip along grain boundaries in orthoclase and plagioclase, and via transgranular fracture (micro-cracking) in quartz. The formation of SiO₂- and TiO₂-rich spheroids on fracture surfaces indicates that temperatures in excess of 3500 K are reached during fracture.     

Blood flow in the rabbit aortic arch and descending thoracic aorta

The distribution of atherosclerotic lesions within the rabbit vasculature, particularly within the descending thoracic aorta, has been mapped in numerous studies. The patchy nature of such lesions has been attributed to local variation in the pattern of blood flow. However, there have been few attempts to model and characterize the flow. In this study, a high-order continuous Galerkin finite-element method was used to simulate blood flow within a realistic representation of the rabbit aortic arch and descending thoracic aorta. The geometry, which was obtained from computed tomography of a resin corrosion cast, included all vessels originating from the aortic arch (followed to at least their second generation) and five pairs of intercostal arteries originating from the proximal descending thoracic aorta. The simulations showed that small geometrical undulations associated with the ductus arteriosus scar cause significant deviations in wall shear stress (WSS). This finding highlights the importance of geometrical accuracy when analysing WSS or related metrics. It was also observed that two Dean-type vortices form in the aortic arch and propagate down the descending thoracic aorta (along with an associated skewed axial velocity profile). This leads to the occurrence of axial streaks in WSS, similar in nature to the axial streaks of lipid deposition found in the descending aorta of cholesterol-fed rabbits. Finally, it was observed that WSS patterns within the vicinity of intercostal branch ostia depend not only on local flow features caused by the branches themselves, but also on larger-scale flow features within the descending aorta, which vary between branches at different locations. This result implies that disease and WSS patterns in the vicinity of intercostal ostia are best compared on a branch-by-branch basis.     

On Homogeneous Nucleation of Dislocation Loops in Nanocrystalline Materials

In this article, we readdress the question of homogeneous nucleation of dislocation loops in the context of nanocrystalline materials. In this case, the commonly adopted assumption of an infinite medium is no longer valid, and image forces on dislocations must be accounted for in the analysis. An additional energy term associated with the presence of finite boundaries may act to promote homogeneous nucleation and growth of dislocation loops. Based on a simplified consideration of a circular dislocation loop in a spherical nanoparticle or nanosized grain in a polycrystal, energy calculations are carried out to estimate the activation energy for homogeneous nucleation of a dislocation loop in such a system. Two different cases are considered: (1) a single nanoparticle and (2) a grain in a polycrystalline nanomaterial. Based on simulations for aluminum, it is shown that this mechanism may be plausible in both cases, albeit only for small particles and grains in the nanometer range.     

Forming Nanocrystalline Structures in Metal Particle Impact

Grain refinement by plastic deformation is becoming increasingly popular as a way of producing metals with improved properties, such as higher mechanical strength. Surface treatment techniques in which a metallic substrate is bombarded with metallic particles can generate nanocrystalline layers in the impact zone. Understanding the physical mechanisms underlying this grain refinement is crucial for achieving an improvement of existing experimental processes. In this article, we propose a numerical framework combining finite element (FE) simulations with a dislocation-based material model to predict the evolution of the microstructure under particle impact. A single particle normally impacting on a metallic substrate was simulated at different initial velocities. The simulations were compared with previously reported numerical and experimental data. The results indicate that our model accurately captures the grain refinement in the impact zone for a broad range of velocities. This approach provides valuable information on the formation of nanocrystalline layers in both the substrate and the impacting particle. Its potential applications include processes involving surface treatment by high velocity particles, such as shot peening, surface mechanical attrition treatment, kinetic metallization, cold spray, etc.     

Cell design in bacteria as a convex optimization problem

In this paper, we investigate the prediction of the cell composition of bacteria with respect to their medium. By modeling the bacterium as an interconnection of subsystems, the problem is written as a non-smooth convex optimization problem equivalent to a Linear Programming feasibility problem. We then obtain a new method, called Resource Balance Analysis (RBA), predicting the distribution of the available resources in the medium among the various cellular subsystems. Beyond its predictive capability, the proposed approach grasps some fundamental aspects of the bacterium physiology by including a refined model. This method reveals the existence of an intrinsic bottleneck in the system resource distribution of the bacterium, leading to the existence of a structural limitation of its growth rate which can be predicted. RBA is also able to predict the configuration of the metabolic network for a given medium at steady-state regimen which nicely fits the available experimental results for the gram-positive model bacterium Bacillus subtilis.     

Exact solution of a plastic hollow sphere with a Mises–Schleicher matrix

In this paper we establish the exact solution for a hollow sphere with a rigid-plastic pressure-sensitive matrix and subjected to hydrostatic tension or compression. The matrix is assumed to obey to a parabolic Mises–Schleicher criterion. The closed-form expressions of the velocity field and of the stress field are provided. These exact solutions, expressed by means of the Lambert W function, allow to assess and discuss existing results.     

Assessing the effect of nutrient mitigation measures in the watersheds of the Southern Bight of the North Sea

The Seine, Somme, and Scheldt Rivers (France, Belgium, and Netherlands) are the major delivering rivers flowing into the continental coastal zone of the Southern Bight of the North Sea, an area regularly affected by eutrophication problems. In the present work, the Seneque-Riverstrahler model was implemented in a multi-regional case study in order to test several planned mitigation measures aimed at limiting stream nutrient contamination and restoring balanced nutrient ratios at the coastal zone.This modeling approach, which is spatially distributed at the basin scale, allows assessing the impact of any change in human activities, which widely differ over the three basins. Here, we define realistic scenarios based on currently proposed measures to reduce point and non-point sources, such as the upgrading of wastewater treatment, the introduction of catch crops, and the development of extensive farming. An analysis of the current situation showed that a 47-72% reduction in P point-source emissions within the three basins could be reached if the intended P treatment was generalized to the largest treatment plants. However, only an overall 14-23% reduction in N could be achieved at the outlet of the three basins, by combining improved wastewater treatment and land use with management measures aimed at regulating agricultural practices. Nonetheless, in spite of these efforts, N will still be exported in large excess with respect to the equilibrium defined by the Redfield ratios, even in the most optimistic hypothesis describing the long-term response of groundwater nitrate concentrations.A comprehensive assessment of these mitigation measures supports the need for additional reductions of nutrient losses from agriculture to control harmful algae development. It also stresses the relevance of this mechanistic approach, in which nutrient transfers from land to sea can be calculated, as an integrated strategy to test policy recommendations.