Pyrazolonderivate. III. [2] Ein Beitrag zur Stereochemie von N,N-disubstituierten 4-Aminomethylen-3-methyl-1-phenyl-Δ2-pyrazolinonen-(5)

Pyrazolone Derivatives. III. A Contribution to Stereochemistry of N, N-Disubstituted 4-Aminomethylene-3-methyl-1-phenyl-Δ²-pyrazolinones-(5) The N,N-disubstituted 4-aminomethylene-Δ²-pyrazolinones-(5) 1 and 2 show a hindered internal rotation around the bond indicating a considerable polarisation of the system. This assumption is supported by i.r.-spectroscopic measurements which show that the CO-bond order decreases with increasing solvent polarity. Compounds 1 and 2 exist in the Z-configuration relative to the exocyclic CC-double bond. That can be attributed to a steric hindrance in the E-configuration of the aminomethylene-substituents with the methyl-group at the pyrazolone-ring.     

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

Enabling Coarse X-ray Fluorescence Imaging Scans with Enlarged Synchrotron Beam by Means of Mosaic Crystal Defocusing Optics

Trace elements, functionalized nanoparticles and labeled entities can be localized with sub-mm spatial resolution by X-ray fluorescence imaging (XFI). Here, small animals are raster scanned with a pencil-like synchrotron beam of high energy and low divergence and the X-ray fluorescence is recorded with an energy-dispersive detector. The ability to first perform coarse scans to identify regions of interest, followed by a close-up with a sub-mm X-ray beam is desirable, because overall measurement time and X-ray dose absorbed by the (biological) specimen can thus be minimized. However, the size of X-ray beams at synchrotron beamlines is usually strongly dependent on the actual beamline setup and can only be adapted within specific pre-defined limits. Especially, large synchrotron beams are non-trivial to generate. Here, we present the concept of graphite-based, convex reflection optics for the one-dimensional enlargement of a 1 mm wide synchrotron beam by a factor of 5 to 10 within a 1 m distance. Four different optics are tested and characterized and their reflection properties compared to ray tracing simulations. The general shape and size of the measured reflection profiles agree with expectations. Enhancements with respect to homogeneity and efficiency can be expected with improved optics manufacturing. A mouse phantom is used for a proof-of-principle XFI experiment demonstrating the applicability of coarse and fine scans with the suggested optics design.     

The hawk/goose story: The classical ethological experiments of Lorenz and Tinbergen, revisited.

We present a historical account of the story behind the famous hawk/goose experiments of Lorenz and Tinbergen in a wider context of cognitive ethology. We discuss their significance, for ethological experimentation in general, and specifically for understanding innate constraints on cognition. As examples of the continuing significance of the hawk/goose paradigm of selective habituation, we discuss its relation to “exposure therapy” of human phobias and the use of hawk silhouettes as deterrents for songbirds. Finally we rephrase Uexküll's thesis of taxon-specific worlds (“Umwelten”) as a “Theory of World.” (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A fast Monte Carlo algorithm for studying bottle-brush polymers

Obtaining reliable estimates of the statistical properties of complex macromolecules by computer simulation is a task that requires high computational effort as well as the development of highly efficient simulation algorithms. We present here an algorithm combining local moves, the pivot algorithm, and an adjustable simulation lattice box for simulating dilute systems of bottle-brush polymers with a flexible backbone and flexible side chains under good solvent conditions. Applying this algorithm to the bond fluctuation model, very precise estimates of the mean square end-to-end distances and gyration radii of the backbone and side chains are obtained, and the conformational properties of such a complex macromolecule are studied. Varying the backbone length (from Nb=67 to Nb=1027), side chain length (from N=0 to N=24 or 48), the scaling predictions for the backbone behavior as well as the side chain behavior are checked. We are also able to give a direct comparison of the structure factor between experimental data and the simulation results.     

A fully automated calibration method for an optical see-through head-mounted operating microscope with variable zoom and focus

Ever since the development of the first applications in image-guided therapy (IGT), the use of head-mounted displays (HMDs) was considered an important extension of existing IGT technologies. Several approaches to utilizing HMDs and modified medical devices for augmented reality (AR) visualization were implemented. These approaches include video-see through systems, semitransparent mirrors, modified endoscopes, and modified operating microscopes. Common to all these devices is the fact that a precise calibration between the display and three-dimensional coordinates in the patient's frame of reference is compulsory. In optical see-through devices based on complex optical systems such as operating microscopes or operating binoculars-as in the case of the system presented in this paper-this procedure can become increasingly difficult since precise camera calibration for every focus and zoom position is required. We present a method for fully automatic calibration of the operating binocular Varioscope M5 AR for the full range of zoom and focus settings available. Our method uses a special calibration pattern, a linear guide driven by a stepping motor, and special calibration software. The overlay error in the calibration plane was found to be 0.14-0.91 mm, which is less than 1% of the field of view. Using the motorized calibration rig as presented in the paper, we were also able to assess the dynamic latency when viewing augmentation graphics on a mobile target; spatial displacement due to latency was found to be in the range of 1.1-2.8 mm maximum, the disparity between the true object and its computed overlay represented latency of 0.1 s. We conclude that the automatic calibration method presented in this paper is sufficient in terms of accuracy and time requirements for standard uses of optical see-through systems in a clinical environment.     

Reduced-Complexity Near-Maximum-Likelihood Detection for Decision Feedback Assisted Space-Time Equalization

A novel decision-feedback (DF) aided reduced complexity maximum likelihood (ML) space-time equalizer (STE) designed for a single-carrier system is introduced. Two different methods of incorporating DF into the recursive tree search based receiver structure are proposed for allowing detection at a moderate computational cost. Additionally, a further complexity reduction scheme is proposed, which exploits the specific characteristics of both the wide-band channel and the proposed DF-STE. In comparison to the DF-STE not benefiting from this complexity reduction, the proposed detector is capable of reducing the complexity by several orders of magnitude. More quantitatively, for the specific rank-deficient system considered, which detected the signal transmitted from four transmit antennas with the aid of two receive antennas, the complexity might be reduced by a factor of 100 at low Signal-to-noise ratios (SNRs) without noticeable performance degradation. By contrast, at higher SNRs a complexity reduction of a factor of 10 might be achieved, depending on the tolerable performance degradation.     

Insights into the In Vitro Formation of Apatite from Mg-Stabilized Amorphous Calcium Carbonate

A protein-free formation of bone-like apatite from amorphous precursors through ball-milling is reported. Mg²⁺ ions are crucial to achieve full amorphization of CaCO₃. Mg²⁺ incorporation generates defects which strongly retard a recrystallization of ball-milled Mg-doped amorphous calcium carbonate (BM-aMCC), which promotes the growth of osteoblastic and endothelial cells in simulated body fluid and has no effect on endothelial cell gene expression. Ex situ snapshots of the processes revealed the reaction mechanisms. For low Mg contents (<30%) a two phase system consisting of Mg-doped amorphous calcium carbonate (ACC) and calcite “impurities” was formed. For high (>40%) Mg²⁺ contents, BM-aMCC follows a different crystallization path via magnesian calcite and monohydrocalcite to aragonite. While pure ACC crystallizes rapidly to calcite in aqueous media, Mg-doped ACC forms in the presence of phosphate ions bone-like hydroxycarbonate apatite (dahllite), a carbonate apatite with carbonate substitution in both type A (OH⁻) and type B (PO₄³⁻) sites, which grows on calcite “impurities” via heterogeneous nucleation. This process produces an endotoxin-free material and makes BM-aMCC an excellent “ion storage buffer” that promotes cell growth by stimulating cell viability and metabolism with promising applications in the treatment of bone defects and bone degenerative diseases.