Fast Signal-Averaging Unit for Ultrasonic Testing: Characterization of Materials Properties and SNR-Improvement for Coarse Grained Materials

The scattering of ultrasonic waves depends on the relation scatterer diameter to wavelength. Coarse grained materials and high frequency ultrasonic waves therefore ere exciting high scattering amplitudes. During pulse-echo testing a backscattering signal is the result of superimposing all the single scattering processes in the sound beam for a given time of flight. Rectifying, digitizing and adding up several A-scans from several different probe positions, angles of incidence or frequencies equalizes interference maxima and minima. The resulting backscattering curve can be evaluated qualitatively and quantitatively for the materials structure characterization. Additionally, an improvement of the signal-to-noise ratio (SNR) is achieved for a defect surrounded by a coarse grained structure. The application in practice depends among other things on the time in which a sufficient number of digitized A-scans is averaged and on the dimensions and operating conditions of the equipment. With these limits a prototype instrument was developed. Up to 1024 digitized A-scans (each 400 ps long, digitizing rate 20 MHz) are averaged in 0.4 sec. The result is recorded on a CRT-display and the whole unit is microcomputer-controlled. The equipment consists of an ultrasonic instrument (USIP 11) and the averager unit (averager, ADC,display, μP). Examples are given of applications to the characterization of materials structure (detection of heterogeneities in steel, grain size determination) and to the ultrasonic testing of coarse grained materials( austenitic welds, castings, fibre reinforced plastics)

FACADE RECONSTRUCTION FOR TEXTURED LOD2 CITYGML MODELS BASED ON DEEP LEARNING AND MIXED INTEGER LINEAR PROGRAMMING

The paper describes a workflow for generating LoD3 CityGML models (i.e. semantic building models with structured facades) based on textured LoD2 CityGML models by adding window and door objects. For each wall texture, bounding boxes of windows and doors are detected using “Faster R-CNN”, a deep neural network. We evaluate results for textures with different resolutions on the ICG Graz50 facade dataset. In general, detected bounding boxes match very well with the rectangular shape of most wall openings. Thus, no further classification of shapes is required. Windows are typically aligned to rows and columns, and only a few different types of windows exist for each facade. However, the neural network proposes rectangles of varying sizes, which are not always aligned perfectly. Thus, we use post-processing to obtain a more realistic appearance of facades. Window and door rectangles get aligned by solving a mixed integer linear optimization problem, which automatically leads to a clustering of these openings into few different classes of window and door types. Furthermore, an a-priori knowledge about the number of clusters is not required

Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs

A progressive neurological disorder was identified in purebred Dalmatian dogs. The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Two affected littermates were euthanized at approximately 7 years, 5 months and 8 years, 2 months of age due to the severity of neurological impairment. The mother of the affected dogs and four other relatives exhibited milder, later-onset neurological signs. Pronounced accumulations of autofluorescent intracellular inclusions were found in cerebral cortex, cerebellum, optic nerve, and cardiac muscle of the affected dogs. These inclusions co-localized with immunolabeling of the lysosomal marker protein LAMP2 and bound antibodies to mitochondrial ATPase subunit c, indicating that the dogs suffered from a lysosomal storage disease with similarities to the neuronal ceroid lipofuscinoses. Ultrastructural analysis indicated that the storage bodies were surrounded by a single-layer membrane, but the storage granules were distinct from those reported for other lysosomal storage diseases. Whole genome sequences, generated with DNA from the two euthanized Dalmatians, both contained a rare, homozygous single-base deletion and reading-frame shift in CNP which encodes the enzyme CNPase (EC 3.1.4.37). The late-onset disease was exhibited by five of seven related Dalmatians that were heterozygous for the deletion allele and over 8 years of age, whereas none of 16 age-matched reference-allele homozygotes developed neurologic signs. No CNPase antigen could be detected with immunohistochemical labeling in tissues from the dogs with the earlier-onset disorder. Similar to the later-onset Dalmatians, autofluorescent storage granules were apparent in brain and cardiac tissue from transgenic mice that were nullizygous for Cnp. Based on the clinical signs, the histopathological, immunohistochemical, ultrastructural, and molecular-genetic findings, and the finding that nullizygous Cnp mice accumulate autofluorescent storage granules, we propose that the earlier-onset Dalmatian disorder is a novel lysosomal storage disease that results from a loss-of-function mutation in CNP and that shares features characteristic of the neuronal ceroid lipofuscinoses. That the later-onset disorder occurred only in dogs heterozygous for the CNP deletion variant suggests that this disorder is a result of the variant allele’s presence

ITERATIVE CLOSEST POINT ALGORITHM FOR ACCURATE REGISTRATION OF COARSELY REGISTERED POINT CLOUDS WITH CITYGML MODELS

The Iterative Closest Point algorithm (ICP) is a standard tool for registration of a source to a target point cloud. In this paper, ICP in point-to-plane mode is adopted to city models that are defined in CityGML. With this new point-to-model version of the algorithm, a coarsely registered photogrammetric point cloud can be matched with buildings’ polygons to provide, e.g., a basis for automated 3D facade modeling. In each iteration step, source points are projected to these polygons to find correspondences. Then an optimization problem is solved to find an affine transformation that maps source points to their correspondences as close as possible. Whereas standard ICP variants do not perform scaling, our algorithm is capable of isotropic scaling. This is necessary because photogrammetric point clouds obtained by the structure from motion algorithm typically are scaled randomly. Two test scenarios indicate that the presented algorithm is faster than ICP in point-to-plane mode on sampled city models

Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction

Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity

Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3. A searchable web interface is accessible via www.mpinat.mpg.de/myelin. Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans

Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation

The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differ- entiation. The hypomethylated regions strongly overlapped with mapped binding sites of the key neuronal transcription factor NEUROD2. The 5-methylcytosine oxidase ten-eleven translocation 2 (TET2) interacted with NEUROD2, and its reaction product 5-hydroxymethylcytosine accumulated at the demethylated regions. NEUROD2-targeted differentially methylated regions retained higher methylation levels in Neurod2 knockout mice, and inducible expression of NEUROD2 caused TET2-associated demethylation at its in vivo binding sites. The data suggest that the reorganization of DNA methylation in developing neurons involves NEUROD2 and TET2-mediated DNA demethylation

Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities