Die Erhöhung des Nutzerkomforts von Fußgängerbrücken mit Massendämpfern am Beispiel des August‐Wilhelm‐Stegs in Oranienburg

Aufgrund ihrer schlanken Bauweise gelten viele Fußgängerbrücken bei personeninduzierten Belastungen als schwingungsanfällig. Die eventuelle Ausstattung einer Brücke mit zusätzlichen Dämpfungsmaßnahmen sollte bereits in der Planungsphase berücksichtigt werden, damit bei Gewissheit, dass Maßnahmen notwendig sind, die Fertigstellung und Eröffnung der Brücke nicht verzögert wird. Im vorliegenden Beitrag wird am Beispiel des August‐Wilhelm‐Stegs in Oranienburg das Vorgehen zwischen Erkennen einer möglichen Schwingungsanfälligkeit, Prüfung der Erforderlichkeit schwingungsdämpfender Maßnahmen, Auslegung und Einbau sowie Überprüfung der Wirksamkeit erläutert. Dabei werden insbesondere die praktischen Aspekte bei der Auslegung der Massendämpfer erläutert. The increasing comfort of footbridges with mass dampers is exemplary shown with the August‐Wilhelm‐Steg in Oranienburg, Germany. Many footbridges are susceptible to pedestrian induced vibrations due to their slender design. Hence, an equipment with additional damping devices on demand should be considered already in the preliminary design phase to avoid unnecessary delays of the erection and opening, if the damping devices are required. In this article the procedure of identifying a potential vibration susceptibility, checking the necessity of damping devices, design and installation as well as checking the working efficiency of them are explained using the example of the August‐Wilhelm‐Steg in Oranienburg. Particular emphasis is laid on the practical aspects when designing tuned mass dampers.     

Doping efficiency and energy-level scheme in C60F48-doped zinc–tetraphenylporphyrin films

High resolution synchrotron-based core level spectroscopy was used to examine the energy level alignment at the interface of zinc–tetraphenylporphyrin films doped by the surface acceptor C₆₀F₄₈. Two distinct fluorofullerene charge states were identified, corresponding to ionized and neutral molecules, and their relative concentration as a function of coverage was used to evaluate the probability of occupation of the acceptor lowest unoccupied molecular orbital (LUMO). From an initial acceptor energy of ?0.25 eV, the C₆₀F₄₈ LUMO shifts upwards with coverage due to a doping-induced interfacial dipole potential, and stabilization of the LUMO at an energy 0.45 eV above the Fermi energy was obtained. While the energy difference upon saturation is consistent with the results obtained for other donor–acceptor systems that have been interpreted as Fermi level pinning, the present work shows that the energy offset is a direct consequence of the interplay between Fermi–Dirac statistics in combination with the interfacial dipole potential.     

Impact of ethanol content on the scavenging activities of oak wood C‐glycosidic ellagitannins. Application to the evaluation of the nutritional status of spirits

As a consequence of their structure, ellagitannins have a high level of activity in terms of their oxidative properties. In particular, their scavenging activity is often presented as a noteworthy parameter, since polyphenols have a beneficial impact on human health. A large variety of spirits, brandies and whiskeys are aged in barrels or receive a wood extract rich in polyphenols. Although spirits (alcoholic beverages) represent a very dynamic market with significant growth, very few scientific papers have been published on this topic, or have justified specific research in this field. Firstly, the scavenging properties of ellagitannins when measured in a solution are presented. An oak wood extract was fractionated by gel chromatography to obtain different fractions with different polymeric levels. It is particularly clear that the oligomer forms are the most efficient by comparison with low‐weight and high‐weight fractions. A mixture of ellagitannins has a higher scavenging intensity than the pure molecule; this illustrates the synergic effect of polyphenols. The scavenging activity of different commercial spirits depends on the presence and quantities of ellagitannins. As an example, the percentage of scavenged superoxide anion radicals represents 70 and 18%, respectively, for spirits aged in a barrel (12 years) and white spirits. In a second step, details of the influence of ethanol on the antioxidant properties of ellagitannins are provided. In particular, alcohol increases the scavenging activity of ellagitannins from 0 to 25% vol., and higher concentrations present a certain degree of pro‐oxidant activity. The chemical study of ellagitannin scavenging properties in solution is confirmed by means of a specific in vitro investigation on the DNA extracted from cells, and directly on the cells. Copyright © 2013 The Institute of Brewing & Distilling     

Surface Binding of TOTAPOL Assists Structural Investigations of Amyloid Fibrils by Dynamic Nuclear Polarization NMR Spectroscopy

Dynamic nuclear polarization (DNP) NMR can enhance sensitivity but often comes at the price of a substantial loss of resolution. Two major factors affect spectral quality: low‐temperature heterogeneous line broadening and paramagnetic relaxation enhancement (PRE) effects. Investigations by NMR spectroscopy, isothermal titration calorimetry (ITC), and EPR revealed a new substantial affinity of TOTAPOL to amyloid surfaces, very similar to that shown by the fluorescent dye thioflavin‐T (ThT). As a consequence, DNP spectra with remarkably good resolution and still reasonable enhancement could be obtained at very low TOTAPOL concentrations, typically 400 times lower than commonly employed. These spectra yielded several long‐range constraints that were difficult to obtain without DNP. Our findings open up new strategies for structural studies with DNP NMR spectroscopy on amyloids that can bind the biradical with affinity similar to that shown towards ThT.     

An Experimental Comparison of the Maintainability of Object-Oriented and Structured Design Documents

Several important questions still need to be answered regarding the maintainability of object-oriented design documents. This paper focuses on the following issues: are object-oriented design documents easier to understand and modify than structured design documents? Do they need to comply with quality guidelines such as the ones provided by Coad and Yourdon? What is the impact of such quality standards on the understandability and modifiability of design documents? Answers can be based on informed opinion or empirical evidence. Since software technology investments are substantial and contradictory opinions exist regarding design strategies, performing empirical studies on these topics is a relevant research activity. This paper presents a controlled experiment performed with computer science students as subjects. Results strongly suggest that quality guidelines based on Coad and Yourdon principles have a beneficial effect on the maintainability of object-oriented design documents. However, there is no strong evidence regarding the alleged higher maintainability of object-oriented design documents over structured design documents. Furthermore, results suggest that object-oriented design documents are more sensitive to poor design practices, in part because their cognitive complexity becomes increasingly unmanageable. However, because our ability to generalise these results is limited, they should be considered as preliminary, i.e., it is very likely that they can only be generalised to programmers with little object-oriented training and programming experience. Such programmers can, however, be commonly found on maintenance projects. As well as additional research, external replications of this study are required to confirm the results and achieve confidence in these findings.     

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.     

Getting a Grip on the Undrugged: Targeting β-Catenin with Fragment-Based Methods

Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential therapeutic strategy. Here, we report the fragment-based discovery of a small molecule binder to β-catenin, including the structural elucidation of the binding mode by X-ray crystallography. The difficulty in drugging β-catenin was confirmed as the primary screening campaigns identified only few and very weak hits. Iterative virtual and NMR screening techniques were required to discover a compound with sufficient potency to be able to obtain an X-ray co-crystal structure. The binding site is located between armadillo repeats two and three, adjacent to the BCL9 and TCF4 binding sites. Genetic studies show that it is unlikely to be useful for the development of protein–protein interaction inhibitors but structural information and established assays provide a solid basis for a prospective optimization towards β-catenin proteolysis targeting chimeras (PROTACs) as alternative modality.     

Modulation of Transaminase Activity by Encapsulation in Temperature-Sensitive Poly(N-acryloyl glycinamide) Hydrogels

Smart hydrogels hold much potential for biocatalysis, not only for the immobilization of enzymes, but also for the control of enzyme activity. We investigated upper critical solution temperature-type poly N-acryloyl glycinamide (pNAGA) hydrogels as a smart matrix for the amine transaminase from Bacillus megaterium (BmTA). Physical entrapment of BmTA in pNAGA hydrogels results in high immobilization efficiency (>89 %) and high activity (97 %). The temperature-sensitiveness of pNAGA is preserved upon immobilization of BmTA and shows a gradual deswelling upon temperature reduction. While enzyme activity is mainly controlled by temperature, deactivation tended to be higher for immobilized BmTA (≈62–68 %) than for free BmTA (≈44 %), suggesting a deactivating effect due to deswelling of the pNAGA gel. Although the deactivation in response to hydrogel deswelling is not yet suitable for controlling enzyme activity sufficiently, it is nevertheless a good starting point for further optimization.