Genomic characteristics of invasive mucinous adenocarcinoma of the lung with multiple pulmonary sites of involvement

Invasive mucinous adenocarcinoma (IMA) of the lung frequently presents with diffuse pneumonic-type features or multifocal lesions, which are regarded as a pattern of intrapulmonary metastases. However, the genomics of multifocal IMAs have not been well studied. We performed whole exome sequencing on samples taken from 2 to 5 regions in seven patients with synchronous multifocal IMAs of the lung (24 regions total). Early initiating driver events, such as KRAS, NKX2-1, TP53, or ARID1A mutations, are clonal mutations and were present in all multifocal IMAs in each patient. The tumor mutational burden of multifocal IMAs was low (mean: 1.13/mega base), but further analyses suggested intra-tumor heterogeneity. The mutational signature analysis found that IMAs were predominantly associated with endogenous mutational process (signature 1), APOBEC activity (signatures 2 and 13), and defective DNA mismatch repair (signature 6), but not related to smoking signature. IMAs synchronously located in the bilateral lower lobes of two patients with background usual interstitial pneumonia had different mutation types, suggesting that they were double primaries. In conclusion, genomic evidence found in this study indicated the clonal intrapulmonary spread of diffuse pneumonic-type or multifocal IMAs, although they can occur in multicentric origins in the background of usual interstitial pneumonia. IMAs exhibited a heterogeneous genomic landscape despite the low somatic mutation burden. Further studies are warranted to determine the clinical significance of the genomic characteristics of IMAs in expanded cohorts.

Modelling and Simulation of Mechanical Loads and Residual Stresses in Deep Rolling at Elevated Temperature

Based on the concept of Process Signatures, the deep rolling process is analyzed, aiming at functional relationships between material modifications and internal material loads during the process. The focus of this work is to investigate the influence of the workpiece temperature on the generated residual stress components. For this purpose, extensive finite element simulations of deep rolling were conducted, taking into account the effect of neighboring tool paths on the internal material loads and residual stress. A kinematic strain hardening model was parameterized and utilized and the simulations were validated experimentally. Simulated residual stresses agree qualitatively well with measurements and show a strong influence of the workpiece temperature as expected. Process Signature Components were generated, taking into account the maximal and minimal residual stress as well as their respective positions beneath the workpiece surface.

Dependence of LPBF Surface Roughness on Laser Incidence Angle and Component Build Orientation

Laser Powder Bed Fusion (LPBF) of metallic components is unlocking new design options for high efficiency gas turbine component designs not possible by conventional manufacturing technologies. Surface roughness is a key characteristic of LPBF components that impacts heat transfer correlations and crack initiation from co-located surface defects — both are critical for gas turbine component durability and performance. However, even for a single material, there is an increasing diversity in laser machines (single vs multi-laser), layer thicknesses (∼20–80 microns) and orientations to the build plate (upskin, vertical and downskin) that result in significant variability in surface roughness. This study systematically compares the surface roughness across the above-mentioned variables to further develop a repeatable correlation of surface roughness to the angle between the substrate normal and laser incidence direction. This presented data will be discussed in detail, to show potential applicability of this process signature curve across materials, machines, and substrate orientations. Future steps to a rapid process qualification standard for surface roughness, across Siemens Energy’s global manufacturing footprint will also be discussed.

An Investigation on Internal Material Loads and Modifications in Precision Turning of Steel 42CrMo4

The functional properties of a workpiece are determined by a modification of the surface and subsurface materials. In this work, the correlation between thermo-mechanical material loads and the modification of the residual stresses is presented. While the resulting residual stresses were measured by X-ray diffraction after machining experiments, the material loads were determined using a process simulation. The experimental data (measured process forces and results from previous experiments) are used to validate the simulation, which is then applied to calculate the internal thermo-mechanical loads of the maximal temperature and the equivalent von-Mises-stresses per volume element during the machining experiments. In conclusion, a higher depth impact of mechanical loads compared to a lower depth impact of thermal loads in precision machining is observed. For the sake of novelty, the thermo-mechanical loads were plotted and interpreted in a three-dimensional fashion. Finally, cross sections of this mutual representation at certain constant material loads—thermal and mechanical—result in a process signature, which can prospectively improve the prediction of functional workpiece properties.

Process Signature for Laser Hardening

During many manufacturing processes for surface treatment of steel components heat will be exchanged between the environment and the workpiece. The heat exchange commonly leads to temperature gradients within the surface near area of the workpiece, which involve mechanical strains inside the material. If the corresponding stresses exceed locally the yield strength of the material residual stresses can remain after the process. If the temperature increase is high enough additionally phase transformation to austenite occurs and may lead further on due to a fast cooling to the very hard phase martensite. This investigation focuses on the correlation between concrete thermal loads such as temperature and temperature gradients and resulting modifications such as changes of the residual stress, the microstructure, and the hardness respectively. Within this consideration the thermal loads are the causes of the modifications and will be called internal material loads. The correlations between the generated internal material loads and the material modifications will be called Process Signature. The idea is that Process Signatures provide the possibility to engineer the workpiece surface layer and its functional properties in a knowledge-based way. This contribution presents some Process Signature components for a thermally dominated process with phase transformation: laser hardening. The target quantities of the modifications are the change of the residual stress state at the surface and the position of the 1st zero-crossing of the residual stress curve. Based on Finite Element simulations the internal thermal loadings during laser hardening are considered. The investigations identify for the considered target quantities the maximal temperature, the maximal temperature gradient, and the heating time as important parameters of the thermal loads.

Multi-Cycle Process Signature of Laser-Induced Thermochemical Polishing

Laser-induced thermochemical polishing (LCP) is a non-conventional processing technique that uses laser radiation to smooth the surface of self-passivated metallic parts by initiating a localized anodic material dissolution. This technology can be used to selectively micro-polish without the need for masking or thermal and mechanical stress. However, there is still a lack in understanding the surface quality depending on the applied laser machining parameters. This paper takes up the concept of Process Signatures and interprets the surface smoothing as result of multiple, recurring internal material loads of a constant energy amount. The laser-induced thermal impact is identified as the relevant internal material load and is correlated with the surface roughness. This derives an empirical-based functional relation as multi-cycle Process Signature. The experiment results show an exponential decay in surface roughness with increasing cycle loads for titanium, Ti6Al4V, Nitinol, Stellite 21, and metallic glass. The Process Signature of LCP is a solution to a differential equation with respect to the cycle loads. The paper demonstrates how the multi-cycle Process Signature helps determine suitable machining parameters to predict the surface roughness, as well as to scale the polishing rate.