“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans     

Metrological solutions for an adapted inspection of parts and tools of a sheet-bulk metal forming process

Processes of the new production technology sheet-bulk metal forming allow a fast and efficient near-net-shape forming of highly complex parts. Thus the need of energy and raw material as well as the production cycle time can be reduced. In order to guarantee these advantages by avoiding scrap and moreover to ensure the parts’ geometrical requirements, production-related metrological solutions for an adapted inspection of parts and tools of sheet-bulk forming processes have to be developed. To fulfill the demands of the differing measuring tasks two prototypical measurement solutions are under development: a multi-scale multi-sensor fringe projection system allows for holistic inspections in feature adapted resolutions, whereas a fiberscopic fringe projection system captures the forming tool partly between forming steps. For the purpose of evaluating the metrological solutions’ capabilities of capturing the geometry of filigree structures a comparison of both systems is presented in this work. To guarantee realistic results, the performed measuring tasks have to be comparable to the areas of applications both systems were designed for. During the development of the measuring systems the emphasis was put on the inspection of small complex geometries. These are most challenging for fast and reliable optical inspection under production-related conditions. By considering measurements of calibrated standards on the one side as well as of measuring tasks resulting out of real sheet-bulk metal forming processes on the other side a realistic comparison is assured. Next to the measuring systems’ performances also an approach for combining the measurement data of both metrological solutions is shown. By combining the advantages of both measuring systems, highly detailed information for further interpretations of the forming processes can be provided.     

Robust H∞ control with multiple constraints forthe track-following system of an optical disk drive

In this paper, the authors design a tracking controller which satisfies transient response specifications and maintains tracking error within a tolerable limit for the uncertain track-following system of an optical disk drive. To this end, a robust H_∞ control problem, with regional stability constraints and sinusoidal disturbance rejection is considered. The internal model principle is used for rejecting the sinusoidal disturbance caused by eccentric rotation of the disk. The authors show that a condition satisfying the regional stability constraints can be expressed in terms of a linear matrix inequality (LMI) using the Lyapunov theory and S-procedure. Finally, a tracking controller is obtained by solving an LMI optimization problem involving two LMIs. The proposed controller design method is evaluated through an experiment     

Construction of a prototype two-component system from the phosphorelay system TodS/TodT

Two-component systems (TCSs) play key roles in the adaptation of bacteria to environmental changes. In prototype TCSs a single phosphoryl transfer between the sensor kinase and response regulator occurs, whereas phosphorelay TCSs are characterised by a His1-Asp1-His2-Asp2 phosphorylation cascade. The TodS/TodT TCS controls the expression of a toluene degradation pathway and the TodS sensor kinase operates by a three-step internal phosphorelay. Based on TodS we report the construction of a minimal form of TodS, termed as Min-TodS, that contains only three of the seven TodS domains. Min-TodS is composed of the N-terminal PAS sensor domain as well as the C-terminal dimerisation/phosphotransfer domain and catalytic domain of TodS. We have conducted a comparative analysis of the phosphorelay TCS with its prototypal derivative. We demonstrate that Min-TodS binds effector molecules with affinities comparable with those observed for TodS. Min-TodS forms a TCS with TodT and toluene increases the amount of TodT-P. In contrast to TodS, toluene does not stimulate Min-TodS autophosphorylation. The half-life of Min-TodS-P was significantly increased as compared with TodS. Analysis of TodSD500A revealed that the hydrolysis of the acylphosphate of the receiver domain is responsible for the reduced half-life of TodS. The regulation of P(todX) expression by Min-TodS/TodT and TodS/TodT in response to different effectors are compared. The Min-TodS/TodT system was characterized by a higher basal activity but a lower magnitude of response. Data will be discussed in the context that the phosphorelay system appears to be better suited for the control of a degradation pathway for toxic compounds.     

Cores of swirling particle motion in unsteady flows

In nature and in flow experiments particles form patterns of swirling motion in certain locations. Existing approaches identify these structures by considering the behavior of stream lines. However, in unsteady flows particle motion is described by path lines which generally gives different swirling patterns than stream lines. We introduce a novel mathematical characterization of swirling motion cores in unsteady flows by generalizing the approach of Sujudi/Haimes to path lines. The cores of swirling particle motion are lines sweeping over time, i.e., surfaces in the space-time domain. They occur at locations where three derived 4D vectors become coplanar. To extract them, we show how to re-formulate the problem using the Parallel Vectors operator. We apply our method to a number of unsteady flow fields.     

Source mass and positioning system for an accurate measurement of G

We report on a system of well-characterized source masses and their precision positioning system for a measurement of the Newtonian gravitational constant G using atoms as probes. The masses are 24 cylinders of 50 mm nominal radius, 150.2 mm nominal height, and mass of about 21.5 kg, sintered starting from a mixture of 95.3% W, 3.2% Ni, and 1.5% Cu. Density homogeneity and cylindrical geometry have been carefully investigated. The positioning system independently moves two groups of 12 cylinders along the vertical direction by tens of centimeters with a reproducibility of a few microns. The whole system is compatible with a resolution DeltaG/G<10(-4).     

Site‐Specific Surface Functionalization via Microchannel Cantilever Spotting (µCS): Comparison between Azide–Alkyne and Thiol–Alkyne Click Chemistry Reactions

Different types of click chemistry reactions are proposed and used for the functionalization of surfaces and materials, and covalent attachment of organic molecules. In the present work, two different catalyst‐free click approaches, namely azide–alkyne and thiol–alkyne click chemistry are studied and compared for the immobilization of microarrays of azide or thiol inks on functionalized glass surfaces. For this purpose, the surface of glass is first functionalized with dibenzocyclooctyne‐acid (DBCO‐acid), a cyclooctyne with a carboxyl group. Then, the DBCO‐terminated surfaces are functionalized via microchannel cantilever spotting with different fluorescent and nonfluorescent azide and thiol inks. Although both routes work reliably for surface functionalization, the protein binding experiments reveal that using a thiol–alkyne route will obtain the highest surface density of molecular immobilization in such spotting approaches. The obtained achievements and results from this work can be used for design and manufacturing of microscale patterns suitable for biomedical and biological applications.