Hardening of Additive Manufactured 316L Stainless Steel by Using Bimodal Powder Containing Nanoscale Fraction

The particle size distribution significantly affects the material properties of the additively manufactured parts. In this work, the influence of bimodal powder containing nano- and micro-scale particles on microstructure and materials properties is studied. Moreover, to study the effect of the protective atmosphere, the test samples were additively manufactured from 316L stainless steel powder in argon and nitrogen. The samples fabricated from the bimodal powder demonstrate a finer subgrain structure, regardless of protective atmospheres and an increase in the Vickers microhardness, which is in accordance with the Hall-Petch relation. The porosity analysis revealed the deterioration in the quality of as-built parts due to the poor powder flowability. The surface roughness of fabricated samples was the same regardless of the powder feedstock materials used and protective atmospheres. The results suggest that the improvement of mechanical properties is achieved by adding a nano-dispersed fraction, which dramatically increases the total surface area, thereby contributing to the nitrogen absorption by the material.     

Selective Laser Melting of Al-Based Matrix Composites with Al2O3 Reinforcement: Features and Advantages

Aluminum matrix composites (AMC) are of great interest and importance as high-performance materials with enhanced mechanical properties. Al₂O₃ is a commonly used reinforcement in AMCs fabricated by means of various technological methods, including casting and sintering. Selective laser melting (SLM) is a suitable modern method of the fabrication of net-shape fully dense parts from AMC with alumina. The main results, achievements, and difficulties of SLM applied to AMCs with alumina are discussed in this review and compared with conventional methods. It was shown that the initial powder preparation, namely the particle size distribution, sphericity, and thorough mixing, affected the final microstructure and properties of SLMed materials drastically. The distribution of reinforcing particles tends to consolidate the near-melting pool-edges process because of pushing by the liquid–solid interface during the solidification process that is a common problem of various fabrication methods. The achievement of an homogeneous distribution was shown to be possible through both the thorough mixing of the initial powders and the precise optimization of SLM parameters. The strength of the AMCs fabricated by the SLM method was relatively low compared with materials produced by conventional methods, while for superior relative densities of more than 99%, hardness and tribological properties were obtained, making SLM a promising method for the Al-based matrix composites with Al₂O₃.     

Numerical Investigation of Analytical Models of Drug Flux Through Microporated Skin

In this study, drug flux through microporated skin was modeled using detailed numerical solution of the diffusion equation. The results of the modeling were compared to previously published simplified and easy to use analytical equations. Limitations and accuracy of these equations were investigated. Appropriate modifications of the equations were identified to expand them to wider practical applications when pore shape is not circular. Numerical simulations have shown a good accuracy of the new simple equations when these are used within their limits of application.     

Predicting changes in protein stability caused by mutation using sequence‐and structure‐based methods in a CAGI5 blind challenge

Predicting the impact of mutations on proteins remains an important problem. As part of the CAGI5 frataxin challenge, we evaluate the accuracy with which Provean, FoldX, and ELASPIC can predict changes in the Gibbs free energy of a protein using a limited data set of eight mutations. We find that different methods have distinct strengths and limitations, with no method being strictly superior to other methods on all metrics. ELASPIC achieves the highest accuracy while also providing a web interface which simplifies the evaluation and analysis of mutations. FoldX is slightly less accurate than ELASPIC but is easier to run locally, as it does not depend on external tools or datasets. Provean achieves reasonable results while being computational less expensive than the other methods and not requiring a structure of the protein. In addition to methods submitted to the CAGI5 community experiment, and with the aim to inform about other methods with high accuracy, we also evaluate predictions made by Rosetta's ddg_monomer protocol, Rosetta's cartesian_ddg protocol, and thermodynamic integration calculations using Amber package. ELASPIC still achieves the highest accuracy, while Rosetta's catesian_ddg protocol appears to perform best in capturing the overall trend in the data.     

Noncompaction cardiomyopathy is caused by a novel in‐frame desmin (DES) deletion mutation within the 1A coiled‐coil rod segment leading to a severe filament assembly defect

Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVHT with conduction disease and skeletal myopathy. The genetic analysis revealed a novel small in‐frame deletion within the DES gene, p.Q113_L115del, affecting the α‐helical rod domain. Immunohistochemistry analysis of explanted myocardial tissue from the index patient revealed an abnormal cytoplasmic accumulation of desmin and a degraded sarcomeric structure. Cell transfection experiments with wild‐type and mutant desmin verified the cytoplasmic aggregation and accumulation of mutant desmin. Cotransfection experiments were performed to model the heterozygous state of the patients and revealed a dominant negative effect of the mutant desmin on filament assembly. DES:p.Q113_L115del is classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT.     

Structure-Based Neuron Retrieval Across Drosophila Brains

Comparing local neural structures across large sets of examples is crucial when studying gene functions, and their effect in the Drosophila brain. The current practice of aligning brain volume data to a joint reference frame is based on the neuropil. However, even after alignment neurons exhibit residual location and shape variability that, together with image noise, hamper direct quantitative comparison and retrieval of similar structures on an intensity basis. In this paper, we propose and evaluate an image-based retrieval method for neurons, relying on local appearance, which can cope with spatial variability across the population. For an object of interest marked in a query case, the method ranks cases drawn from a large data set based on local neuron appearance in confocal microscopy data. The approach is based on capturing the orientation of neurons based on structure tensors and expanding this field via Gradient Vector Flow. During retrieval, the algorithm compares fields across cases, and calculates a corresponding ranking of most similar cases with regard to the local structure of interest. Experimental results demonstrate that the similarity measure and ranking mechanisms yield high precision and recall in realistic search scenarios.     

In vivo X-ray cine-tomography for tracking morphological dynamics

Scientific cinematography using ultrafast optical imaging is a common tool to study motion. In opaque organisms or structures, X-ray radiography captures sequences of 2D projections to visualize morphological dynamics, but for many applications full four-dimensional (4D) spatiotemporal information is highly desirable. We introduce in vivo X-ray cine-tomography as a 4D imaging technique developed to study real-time dynamics in small living organisms with micrometer spatial resolution and subsecond time resolution. The method enables insights into the physiology of small animals by tracking the 4D morphological dynamics of minute anatomical features as demonstrated in this work by the analysis of fast-moving screw-and-nut–type weevil hip joints. The presented method can be applied to a broad range of biological specimens and biotechnological processes.The best method to study morphological changes of anatomic features and physiological processes is to observe their dynamics in 4D, that is, in real time and in 3D space. To achieve this we have developed in vivo X-ray cine-tomography to gain access to morphological dynamics with unrivaled 4D spatiotemporal resolution. This opens the way to a wide range of hitherto inaccessible, systematic investigations of small animals and biological internal processes such as breathing, circulation, digestion (1), reproduction, and locomotion (2).At the micrometer resolution range, state-of-the-art optical imaging techniques can achieve high magnifications to visualize tissues and even individual cells for 4D studies. These methods however are confined to transparent or fluorescent objects, or are limited either by low penetration depth <1 mm or poor time resolution (3). For optically opaque living organisms X-ray imaging methods are highly appropriate due to the penetrating ability of the radiation. Modern synchrotron radiation facilities provide brilliant and partially coherent radiation suitable for high-resolution volume imaging methods such as X-ray computed microtomography (SR-µCT). For static specimens SR-µCT has proven to be a powerful tool to study small animal morphology in 3D (4–6). The benefits of various physical contrast mechanisms, high spatial resolution, and short measuring times, as well as enormous sample throughput compared with laboratory X-ray setups, have led to its widespread use in life sciences.Real-time in vivo X-ray imaging with micrometer spatial resolution was realized so far by recording time sequences of 2D projection radiographs of different organisms (1, 6, 7), providing time information about functional dynamics but losing any information about the third spatial dimension.Recently, 4D in vivo X-ray experiments have been performed to study cell migration in frog embryos (8, 9) using tomographic sequences of a few seconds exposure time per tomogram interrupted by longer nonexposure time slots. In this way the authors followed relatively slow dynamics and morphological changes during embryonic development with 2-µm resolution over total time intervals of several hours. The fastest 4D time series yet reported were realized with a temporal resolution of 0.5 s and spatial resolution of 25 µm (10), applied to a living caterpillar used as test specimen for imaging, but without any analysis of dynamics.In this paper, we demonstrate the quantitative 4D investigation of morphological dynamics by in vivo X-ray 4D cine-tomography, introduced here as the combination of ultrafast SR-µCT and motion analysis procedures. Using this approach allows us to investigate previously inaccessible 3D morphological dynamics in small animals, presently with feature sizes in the micrometer range and with temporal resolution down to a few tens of milliseconds. In the past, ultrafast in vivo imaging was hardly possible for such applications, due to the strongly competing requirements for simultaneous high contrast, high signal-to-noise ratio (SNR), and concurrent low radiation dose, as well as the need for simultaneous high spatial resolution and maximum temporal resolution.In the following we describe how in vivo X-ray 4D cine-tomography meets the above challenges by optimizing image contrast, SNR, and spatial and temporal resolution in the ultrafast SR-µCT system and by establishing a dedicated data analysis pipeline, all within a unified framework (Fig. S1). We demonstrate the potential of the technique by investigating morphological dynamics in fast-moving weevils, focusing here on the exoskeletal joints.