Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.     

The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.     

Reconfigurable handling system

The demand for more versatile assembly and handling systems to facilitate customized production is gaining in importance, especially with regard to the constantly-increasing cost pressure, to expansion of the range of product versions and the shortening of innovation cycles. As a cost-effective approach for frequently changing assembly tasks, a novel manipulation concept has been developed by combining given robot technologies. This new handling system has a modular and adaptable layout, which consists of several mobile arms to manipulate the object in six-dimensional Cartesian space. After grasping, when the arms are attached to the object, the mechanical architecture is similar to parallel manipulators or cooperating robots. As the mounting and gripping points of the arms can easily be changed, the manipulator can be reconfigured so as to match the user’s preferences and needs. In addition to the kinematic adaption the regarding task, the hardware and new functions can be reconfigured as well. Contact elements, measurement and assembly devices as well as testing modules can easily be in integrated in the concept. A modular automatic control concept combined with a self-optimizing planning tool helps the user to find the optimal configuration and realize it in an economic way.     

Structure,homogeneity ranges,magnetic, and electrical properties of the ordered Laves phases RENi4Mg with MgCu4Sn type structure

New ordered Laves phases RENi₄Mg (RE = Sc, Sm, Tb–Lu) were synthesized from the elements in sealed tantalum ampoules in an induction furnace. Six of the structures were refined on the basis of X-ray single crystal data. The diffraction experiments gave hint for small homogeneity ranges RE_1+xNi₄Mg_1?x. Magnetic susceptibility measurements show Curie–Weiss behavior for RE = Gd, Dy, Ho, Tm, Yb and the resulting effective magnetic moments suggest both stable trivalent states for all RE and a non-magnetic state for Ni. Gd_1+xNi₄Mg_1?x (x ≈ 0.12) orders antiferromagnetically at a Néel temperature of T_N = 4.6(5) K. Resistivity measurements reflect the metallic nature of these compounds.     

Deficits in emotion-regulation skills predict alcohol use during and after cognitive–behavioral therapy for alcohol dependence.

Objective: As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). Method: A prospective study investigated whether emotion-regulation skills were associated with AD and whether these skills predicted alcohol use during and after treatment for AD. Participants were 116 individuals treated for AD with cognitive–behavioral therapy. Emotion regulation and severity of AD symptoms were assessed by self-report. Alcohol use during treatment was assessed by Breathalyzer and urine analysis for ethyl glucuronide; alcohol use during the 3-month follow-up interval was assessed by self-report. Results: Pretreatment emotion-regulation skills predicted alcohol use during treatment, and posttreatment emotion-regulation skills predicted alcohol use at follow-up, even when controlling for other predictors potentially related to emotion regulation. Among a broad range of specific emotion-regulation skills, the ability to tolerate negative emotions was the only skill that negatively predicted subsequent alcohol consumption when controlling for the other skills. Individuals in the AD sample reported significantly larger deficits in emotion-regulation skills than did those in a nonclinical control sample but significantly less than did those in a sample of individuals exclusively meeting criteria for major depressive disorder. Conclusions: Enhancement of general emotion-regulation skills, especially the ability to tolerate negative emotions, appears to be an important target in the treatment of AD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Turbulent boundary layers: is the wall falling or merely wobbling?

A quick passage through five centuries of turbulence research highlights the major milestones. The more recent cornerstones include Kolmogorov??s equilibrium theory of turbulence spectrum, the universal logarithmic law of wall-bounded flows, and the proliferation of direct numerical simulations. Evidence of recent fault lines in all three major achievements is presented, but also novel remedies as well as a few contemporary accomplishments are pointed out.     

Linearisation of asymmetrical Doherty amplifier by the even-order non-linear signals

This paper considers the linearisation of an asymmetrical two-way Doherty amplifier by the method that uses the second harmonics and fourth-order non-linear signals for linearisation. These even-order signals for linearisation are extracted at the output of the peaking amplifier, adjusted in amplitude and phase and injected at the input and output of the carrier amplifier transistor in the Doherty configuration. The effect of linearisation has been experimentally confirmed on a fabricated asymmetrical Doherty amplifier with the additional circuit for linearisation. The suppression of the third-order intermodulation products has been carried out for two-tone test, 64QAM and WCDMA digitally modulated signals in a range of signal power.     

Morphology Transformation Pathway of Block Copolymer-Directed Cooperative Self-Assembly of ZnO Hybrid Films Monitored In Situ during Slot-Die Coating

Cooperative self-assembly (co-assembly) of diblock copolymers (DBCs) and inorganic precursors that takes inspiration from the rich phase separation behavior of DBCs can enable the realization of a broad spectrum of functional nanostructures with the desired sizes. In a DBC assisted sol–gel chemistry approach with polystyrene-block-poly(ethylene oxide) and ZnO, hybrid films are formed with slot-die coating. Pure DBC films are printed as control. In situ grazing-incidence small-angle X-ray scattering measurements are performed to investigate the self-assembly and co-assembly process during the film formation. Combining complementary ex situ characterizations, several distinct regimes are differentiated to describe the morphological transformations from the initially solvent-dispersed to the ultimately solidified films. The comparison of the assembly pathway evidences that the key step in the establishment of the pure DBC film is the coalescence of spherical micelles toward cylindrical domains. Due to the presence of the phase-selective precursor, the formation of cylindrical aggregates in the solution is crucial for the structural development of the hybrid film. The pre-existing cylinders in the ink impede the domain growth of the hybrid film during the subsequent drying process. The precursor reduces the degree of order, prevents crystallization of the PEO block, and introduces additional length scales in the hybrid films.     

Still Image Processing on Coarse-Grained Reconfigurable Array Architectures

Due to the increasing demands on efficiency, performance and flexibility reconfigurable computational architectures are very promising candidates in embedded systems design. Recently coarse-grained reconfigurable array architectures (CGRAs), such as the ADRES CGRA and its corresponding DRESC compiler are gaining more popularity due to several technological breakthroughs in this area. We investigate the mapping of two image processing algorithms, Wavelet encoding and decoding, and TIFF compression on this novel type of array architectures in a systematic way. The results of our experiments show that CGRAs based on ADRES and its DRESC compiler technology deliver improved performance levels for these two benchmark applications when compared to results obtained on a state-of-the-art commercial DSP platform, the c64x DSP from Texas Instruments. ADRES/DRESC can beat its performance by at least 50% in cycle count and the power consumption even drops to 10% of the published numbers of the c64x DSP.