Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53.

Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production. Recruitment of MDM2 to mitochondria increases during oxidative stress and hypoxia. Accordingly, mice lacking MDM2 in skeletal muscles exhibit higher MT-ND6 levels, enhanced complex I activity, and increased muscular endurance in mild hypoxic conditions. Furthermore, increased mitochondrial MDM2 levels enhance the migratory and invasive properties of cancer cells. Collectively, these data uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria that play critical roles in skeletal muscle physiology and may contribute to tumor progression.

Pose Estimation and Damage Characterization of Turbine Blades during Inspection Cycles and Component-Protective Disassembly Processes.

Inspection in confined spaces and difficult-to-access machines is a challenging quality assurance task and particularly difficult to quantify and automate. Using the example of aero engine inspection, an approach for the high-precision inspection of movable turbine blades in confined spaces will be demonstrated. To assess the condition and damages of turbine blades, a borescopic inspection approach in which the pose of the turbine blades is estimated on the basis of measured point clouds is presented. By means of a feature extraction approach, film-cooling holes are identified and used to pre-align the measured point clouds to a reference geometry. Based on the segmented features of the measurement and reference geometry a RANSAC-based feature matching is applied, and a multi-stage registration process is performed. Subsequently, an initial damage assessment of the turbine blades is derived, and engine disassembly decisions can be assisted by metric geometry deviations. During engine disassembly, the blade root is exposed to high disassembly forces, which can damage the blade root and is crucial for possible repair. To check for dismantling damage, a fast inspection of the blade root is executed using the borescopic sensor.

Adapted Fringe Projection Sequences for Changing Illumination Conditions on the Example of Measuring a Wrought-Hot Object Influenced by Forced Cooling.

Optical 3D geometry reconstruction, or more specific, fringe projection profilometry, is a state-of-the-art technique for the measurement of the shape of objects in confined spaces or under rough environmental conditions, e.g., while inspecting a wrought-hot specimen after a forging operation. While the contact-less method enables the measurement of such an object, the results are influenced by the light deflection effect occurring due to the inhomogeneous refractive index field induced by the hot air around the measurand. However, the developed active compensation methods to fight this issue exhibits a major drawback, namely an additional cooling of the object and a subsequent transient illumination component. In this paper, we investigate the cooling and its effect on temporal phase reconstruction algorithms and take a theoretical approach to its compensation. The simulated compensation measures are transferred to a fringe projection profilometry setup and are evaluated using established and newly developed methods. The results show a significant improvement when measuring specimens under a transient illumination and are easily transferable to any kind of multi-frequency phase-shift measurement.

Fringe Projection Profilometry in Production Metrology: A Multi-Scale Comparison in Sheet-Bulk Metal Forming.

Fringe projection profilometry in combination with other optical measuring technologies has established itself over the last decades as an essential complement to conventional, tactile measuring devices. The non-contact, holistic reconstruction of complex geometries within fractions of a second in conjunction with the lightweight and transportable sensor design open up many fields of application in production metrology. Furthermore, triangulation-based measuring principles feature good scalability, which has led to 3D scanners for various scale ranges. Innovative and modern production processes, such as sheet-bulk metal forming, thus, utilize fringe projection profilometry in many respects to monitor the process, quantify possible wear and improve production technology. Therefore, it is essential to identify the appropriate 3D scanner for each application and to properly evaluate the acquired data. Through precise knowledge of the measurement volume and the relative uncertainty with respect to the specimen and scanner position, adapted measurement strategies and integrated production concepts can be realized. Although there are extensive industrial standards and guidelines for the quantification of sensor performance, evaluation and tolerancing is mainly global and can, therefore, neither provide assistance in the correct, application-specific positioning and alignment of the sensor nor reflect the local characteristics within the measuring volume. Therefore, this article compares fringe projection systems across various scale ranges by positioning and scanning a calibrated sphere in a high resolution grid.

Detection of material zones on the surface of a steel-aluminum hybrid component using reflection models and a monochromatic fringe projection profilometry system.

The limits of traditional lightweight engineering are being extended by the development of hybrid components. Lightweight potential is especially high when using dissimilar materials, e.g., a friction-welded steel-aluminum combination. An important factor for the mechanical properties of such a combination is the geometry and location of the joining zone between the materials. The geometry of these objects can be reconstructed by optical triangulation techniques such as fringe projection profilometry. In this paper, we present a method to robustly detect the different material zones on the surface of a hybrid steel-aluminum component. We use reflection models and data from a fringe projection profilometry system. The intensity values and 3D geometry data from the fringe projection system are used to estimate material-specific reflection parameters for each 3D point and detect different material areas based on a global threshold.

Metal Forming Tool Monitoring Based on a 3D Measuring Endoscope Using CAD Assisted Registration.

In order to provide timely, reliable, and comprehensive data for the maintenance of highly stressed geometries in sheet-bulk metal forming tools, this article features a possible setup by combining a 3D measuring endoscope with a two-stage kinematic. The measurement principle is based on the projection of structured light, allowing time-effective measurements of larger areas. To obtain data of proper quality, several hundred measurements are performed which then have to be registered and finally merged into one single point cloud. Factors such as heavy, unwieldy specimens affecting precise alignment. The rotational axes are therefore possibly misaligned and the kinematics and the hand-eye transformation remain uncalibrated. By the use of computer-aided design (CAD) data, registration can be improved, allowing a detailed examination of local features like gear geometries while reducing the sensitivity to detect shape deviations.

Reversible magnetomechanical collapse: virtual touching and detachment of rigid inclusions in a soft elastic matrix.

Soft elastic composite materials containing particulate rigid inclusions in a soft elastic matrix are candidates for developing soft actuators or tunable damping devices. The possibility to reversibly drive the rigid inclusions within such a composite together to a close-to-touching state by an external stimulus would offer important benefits. Then, a significant tuning of the mechanical properties could be achieved due to the resulting mechanical hardening. For a long time, it has been argued whether a virtual touching of the embedded magnetic particles with subsequent detachment can actually be observed in real materials, and if so, whether the process is reversible. Here, we present experimental results that demonstrate this phenomenon in reality. Our system consists of two paramagnetic nickel particles embedded at finite initial distance in a soft elastic polymeric gel matrix. Magnetization in an external magnetic field tunes the magnetic attraction between the particles and drives the process. We quantify our experimental results by different theoretical tools, i.e., explicit analytical calculations in the framework of linear elasticity theory, a projection onto simplified dipole-spring models, as well as detailed finite-element simulations. From these different approaches, we conclude that in our case the cycle of virtual touching and detachment shows hysteretic behavior due to the mutual magnetization between the paramagnetic particles. Our results are important for the design and construction of reversibly tunable mechanical damping devices. Moreover, our projection on dipole-spring models allows the formal connection of our description to various related systems, e.g., magnetosome filaments in magnetotactic bacteria.

Fringe projection system for high-temperature workpieces-design, calibration, and measurement.

In the Collaborative Research Centre 1153, Tailored Forming, the geometry of hot measurement objects needs to be captured quickly, areally, and with high precision. The documentation of the hybrid components' shrinkage behavior directly after the forming process can yield insight into the development of residual stresses. In this paper, we present a fringe projection measurement setup designed for the topography measurement of high-temperature steel shafts, comprising two cameras with different lenses and a projector. In order to separate the measurement signal from light by self-radiation, a green bandpass filter is installed in front of the measurement camera's sensor. The optical sensors are protected from the measurement object's temperature and possible scale by a glass panel and a working distance of at least 250 mm. High-resolution measurements are guaranteed due to a telecentric measurement camera and a triangulation angle of about 30°. The triangulation angle requires an additional entocentric calibration camera to provide a highly accurate projector model estimation. Special attention is therefore devoted to the developed calibration routine, the glass panel effect, and the applied distortion models. The quality of the calibration routine is validated by a reference sphere measurement. Furthermore, the geometry data of a red-glowing heating rod (approximately 1020°C) is acquired to demonstrate the performance of the presented system. In future applications, the presented setup will be used with a force-controlled clamping unit to enable secure and position stable topography acquisition of hot measurement objects.

Background oriented schlieren measurement of the refractive index field of air induced by a hot, cylindrical measurement object.

To optically capture the topography of a hot measurement object with high precision, the light deflection by the inhomogeneous refractive index field-induced by the heat transfer from the measurement object to the ambient medium-has to be considered. We used the 2D background oriented schlieren method with illuminated wavelet background, an optical flow algorithm, and Ciddor's equation to quantify the refractive index field located directly above a red-glowing, hot measurement object. A heat transfer simulation has been implemented to verify the magnitude and the shape of the measured refractive index field. Provided that no forced external flow is disturbing the shape of the convective flow originating from the hot object, a laminar flow can be observed directly above the object, resulting in a sharply bounded, inhomogeneous refractive index field.

High-precision surface measurement with an automated multiangle low coherence interferometer.

We propose a novel measurement system based on a low coherence Michelson interferometer and six-axis hexapod platform to accurately measure structures with high aspect ratio using different tilt angles of the measured surface. In order to realize automatic measurement, the system is designed to automatically perform autofocusing, adjust the tilt angle of the test surface, make surface measurements, and merge the measurement data sets. Due to certain topography, e.g., structures with high aspect ratio, the interferometer cannot obtain enough reflected light to evaluate the height information in some areas of the test surface. For this reason, we developed a measurement system that uses measurements from different tilt angles of the test surface and stitching algorithms to realize a complete surface measurement data set. The performance of the proposed measurement system is evaluated experimentally and compared to the results of measurements using a perthometer.

RGB-D microtopography: A comprehensive dataset for surface analysis and characterization techniques.

The dataset presented contains microtopographies of various materials and processing methods. These microtopographies were measured using a Confocal Laser Scanning Microscope, which provides RGB-D data. This means the dataset comprises accurate height maps for each measurement and microscopic RGB images. The height maps can be used to quantify and characterize small-scale surface features such as pits and grooves, surface roughness, texture direction, and surface anisotropy. These features can significantly impact a material's properties and behavior, making them essential in many fields, such as biomaterials and tribology. Additionally, the dataset contains metadata about the specimens and the measurement conditions, such as material, surface processing method, roughness, and optical magnification. Therefore, this dataset provides an opportunity to develop and test surface classification and characterization algorithms.

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses.

Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA's receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus-cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells. Unexpectedly, we found that HA's receptor binding preference does not necessarily reflect virus-cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAVs, thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.

Estimation of measurement uncertainties using virtual fringe projection technique.

One of the main tasks of the quality test is the inspection of all relevant geometric parts related to the predefined tolerance range, whereas the uncertainty of measurement has to be less than the tolerance range. The reachable uncertainty of measurement can be determined using method A of the ISO Guide to the Expression of Uncertainty in Measurement (GUM), which is expensive and time consuming and has to be carried out for each individual metrologic case. Furthermore, it is possible to check the suitability of the measurement system for the planned inspection using virtual measurement techniques and therewith to reduce the time and money spent. This means that the uncertainty of measurement is estimated using method B of the GUM. In this paper, a virtual fringe projection system is used for the estimation of the uncertainty of measurement, which is compared with the uncertainty of measurement determined with a real measurement system using method A of the GUM. With the presented method, it is possible to calculate an optimal measurement position within the measurement volume, based on a minimum uncertainty of measurement. Thereby, the influence of the operator related to the uncertainty can be significantly reduced.

Benchmark for the Coupled Magneto-Mechanical Boundary Value Problem in Magneto-Active Elastomers.

Within this contribution, a novel benchmark problem for the coupled magneto-mechanical boundary value problem in magneto-active elastomers is presented. Being derived from an experimental analysis of magnetically induced interactions in these materials, the problem under investigation allows us to validate different modeling strategies by means of a simple setup with only a few influencing factors. Here, results of a sharp-interface Lagrangian finite element framework and a diffuse-interface Eulerian approach based on the application of a spectral solver on a fixed grid are compared for the simplified two-dimensional as well as the general three-dimensional case. After influences of different boundary conditions and the sample size are analyzed, the results of both strategies are examined: for the material models under consideration, a good agreement of them is found, while all discrepancies can be ascribed to well-known effects described in the literature. Thus, the benchmark problem can be seen as a basis for future comparisons with both other modeling strategies and more elaborate material models.

Magneto-Mechanical Coupling in Magneto-Active Elastomers.

In the present work, the magneto-mechanical coupling in magneto-active elastomers is investigated from two different modeling perspectives: a micro-continuum and a particle-interaction approach. Since both strategies differ significantly in their basic assumptions and the resolution of the problem under investigation, they are introduced in a concise manner and their capabilities are illustrated by means of representative examples. To motivate the application of these strategies within a hybrid multiscale framework for magneto-active elastomers, their interchangeability is then examined in a systematic comparison of the model predictions with regard to the magneto-deformation of chain-like helical structures in an elastomer surrounding. The presented results show a remarkable agreement of both modeling approaches and help to provide an improved understanding of the interactions in magneto-active elastomers with chain-like microstructures.

Determination of the Entire Stent Surface Area by a New Analytical Method.

Stenting is a widely used treatment procedure for coronary artery disease around the world. Stents have a complex geometry, which makes the characterization of their corrosion difficult due to the absence of a mathematical model to calculate the entire stent surface area (ESSA). Therefore, corrosion experiments with stents are mostly based on qualitative analysis. Additionally, the quantitative analysis of corrosion is conducted with simpler samples made of stent material instead of stents, in most cases. At present, several methods are available to calculate the stent outer surface area (SOSA), whereas no model exists for the calculation of the ESSA. This paper presents a novel mathematical model for the calculation of the ESSA using the SOSA as one of the main parameters. The ESSA of seven magnesium alloy stents (MeKo Laser Material Processing GmbH, Sarstedt, Germany) were calculated using the developed model. The calculated SOSA and ESSA for all stents are 33.34%(±0.26%) and 111.86 mm (±0.85 mm), respectively. The model is validated by micro-computed tomography (micro-CT), with a difference of 12.34% (±0.46%). The value of corrosion rates calculated using the ESSA computed with the developed model will be 12.34% (±0.46%) less than that of using ESSA obtained by micro-CT.

Receptor arrays for the selective and efficient capturing of viral particles.

We describe microarrays of receptors on gold/glass substrates for the selective capturing of viral particles at high density. Microscale gold squares were surface-modified with alkanethiol derivatives which enabled the immobilization of the His(6)-tagged virus-binding domain from the very-low density lipoprotein (VLDL) receptor. The free glass areas surrounding the gold squares were passivated with a dense film of poly(ethylene glycol) (PEG). As assessed by atomic force microscopy, human rhinovirus particles were captured onto the VLDL-receptor patches with a high surface coverage but were effectively repelled by the PEG layer, resulting in a 330 000-fold higher density of the particles on the gold as compared to the glass surfaces. The metal chelate-based coupling strategy was found to be superior to two alternative routes, which used the covalent coupling of viral particles or viral receptors to the substrate surface. The high-density receptor arrays were employed for sensing and characterizing viral particles with so far unprecedented selectivity.

Topography and recognition imaging of protein-patterned surfaces generated by AFM nanolithography.

Native-protein nanolithography is combined with topography and recognition imaging to synergistically use AFM tips to write and image nanoscale protein patterns on a surface (see picture). The approach is validated with different feedback modes, using surface-bound biotinylated bovine serum albumin (BSA) protein and AFM tips carrying streptavidin.

Examination of native and carbamide peroxide-bleached human tooth enamel by atomic force microscopy.

Atomic force microscopy (AFM) was used to study the effects of bleaching on the morphology of the enamel surface with nanoscale resolution. Samples of human tooth enamel with native (pumiced) or fine-polished surfaces were examined before and after bleaching with 30% carbamide peroxide. The obtained profilometric AFM data revealed significant morphological surface alterations. After 1 h of bleaching, the surface roughness increased significantly from 19 +/- 4nm to 33 +/- 5 nm. Six-hour bleaching did not produce any significant further increase in enamel surface roughness. The interrod junction depth raised more than twice after 1 h of bleaching. After 6 h of bleaching, a further and significant increase in interrod junction depth was recorded. This alteration might be a consequence of oxidation and a subsequent partial lysis of the tooth enamel matrix proteins.

Atomic force microscopy-derived nanoscale chip for the detection of human pathogenic viruses.

Native-protein nanolithography (NPNL) was used to fabricate stable bioactive arrays of viral receptor spots. The arrays were specific for the cognate virus and devoid of nonspecific protein and virus adsorption under physiologic conditions. The spot size ranged from 200 nm x 200 nm to 2 microm x 2 microm and up to 3 x 3 spots were arranged per array. With proper force adjustment in the patterning experiments, His(6)-tagged bovine serum albumin (BSA) molecules were selectively removed from the underlying self-assembled monolayer (SAM) while leaving the latter intact. Injection of His(6)-tagged very low density lipoprotein receptor (VLDLR-His(6)) constructs resulted in specific, oriented binding to the Ni(2+)-loaded bis-(nitrolotriacetic acid) (bis-NTA) groups to the re-exposed SAM areas. The arrays of viral receptors were used for the detection of human rhinovirus particles (serotype 2; HRV2) under native conditions by topographical imaging at high signal-to-noise ratio. The kinetic on-rate of the HRV2-VLDLR interaction was derived from the time-dependent binding of the virions to the VLDL receptor spots. No significant binding was observed for the major group virus HRV14 that uses the unrelated receptor ICAM-1.