InAs/GaInAs quantum dot DFB lasers emitting at 1.3 μm

Singlemode operation of 1.3 μm InAs/GaInAs quantum dot lasers has been achieved using the concept of complex coupled distributed feedback. Mode selection was realised by laterally patterned metal gratings. At room temperature the lasers show stable singlemode emission with sidemode suppression ratios of up to 55 dB, threshold currents as low as 17 mA and output powers of up to 8 mW under continuous wave operation     

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.     

Noise peaks influence communication in the operating room. An observational study

Noise peaks are powerful distractors. This study focuses on the impact of noise peaks on surgical teams’ communication during 109 long abdominal surgeries. We related measured noise peaks during 5-min intervals to the amount of observed communication during the same interval. Results show that noise peaks are associated with less case-relevant communication; this effect is moderated by the level of surgical experience; case-relevant communications decrease under high noise peak conditions among junior, but not among senior surgeons. However, case-irrelevant communication did not decrease under high noise level conditions, rather there was a trend to more case-irrelevant communication under high noise peaks. The results support the hypothesis that noise peaks impair communication because they draw on attentional resources rather than impairing understanding of communication. As case-relevant communication is important for surgical performance, exposure to high noise peaks in the OR should be minimised especially for less experienced surgeons.

Practitioner Summary: This study investigated whether noise during surgeries influenced the communication within surgical teams. During abdominal surgeries, noise levels were measured and communication was observed. Results showed that high noise peaks reduced the frequency of patient-related communication, but did not reduce patient-irrelevant communication. Noise may negatively affect team coordination in surgeries.     

Synthesis of an Anti-CD7 Recombinant Immunotoxin Based on PE24 in CHO and E. coli Cell-Free Systems

Recombinant immunotoxins (RITs) are an effective class of agents for targeted therapy in cancer treatment. In this article, we demonstrate the straight-forward production and testing of an anti-CD7 RIT based on PE24 in a prokaryotic and a eukaryotic cell-free system. The prokaryotic cell-free system was derived from Escherichia coli BL21 Star^TM (DE3) cells transformed with a plasmid encoding the chaperones groEL/groES. The eukaryotic cell-free system was prepared from Chinese hamster ovary (CHO) cells that leave intact endoplasmic reticulum-derived microsomes in the cell-free reaction mix from which the RIT was extracted. The investigated RIT was built by fusing an anti-CD7 single-chain variable fragment (scFv) with the toxin domain PE24, a shortened variant of Pseudomonas Exotoxin A. The RIT was produced in both cell-free systems and tested for antigen binding against CD7 and cell killing on CD7-positive Jurkat, HSB-2, and ALL-SIL cells. CD7-positive cells were effectively killed by the anti-CD7 scFv-PE24 RIT with an IC₅₀ value of 15 pM to 40 pM for CHO and 42 pM to 156 pM for E. coli cell-free-produced RIT. CD7-negative Raji cells were unaffected by the RIT. Toxin and antibody domain alone did not show cytotoxic effects on either CD7-positive or CD7-negative cells. To our knowledge, this report describes the production of an active RIT in E. coli and CHO cell-free systems for the first time. We provide the proof-of-concept that cell-free protein synthesis allows for on-demand testing of antibody–toxin conjugate activity in a time-efficient workflow without cell lysis or purification required.     

Multiblend JET A-1 in Practice: Results of an R&D Project on Synthetic Paraffinic Kerosenes

The research and demonstration project, DEMO-SPK, a model project under the German Mobility and Fuel Strategy (MFS), investigated the use of renewable kerosene at the Leipzig/Halle airport. Its primary goal was to examine and verify the behavior of blends consisting of several types of renewable kerosene and fossil JET A-1, under the realistic supply conditions of a major airport. The project demonstrated that the supply chain for multiblend JET A-1 was technically feasible and that the fuel could be used without requiring any changes in the normal operating procedures. The project also confirmed that the use of multiblend JET A-1 resulted in a 30–60% reduction in particulate emissions for ground operations and a reduction in CO₂ equivalents, compared with pure fossil JET A-1.     

Energieeffizienzsteigerung in der Prozesswasseraufbereitung – Untersuchungen zu Bildungsmechanismen von Silikatbelägen

Investigations on the formation mechanisms of silicate films on reverse osmosis membranes and their morphological characteristics are presented. Relevant influencing factors on the formation of coatings are considered and the individual mechanisms are described. Furthermore, the essential characterization characteristics for the investigation of silicate coatings are determined, the applied analysis methods are described and an overview of the sample preparation is given.     

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.     

Fluorescence Lifetime Imaging Microscopy (FLIM) of Intracellular Transport by Means of Doubly Labelled siRNA Architectures

For monitoring the intracellular pathway of small interfering RNA (siRNA), both strands were labelled at internal positions by two ATTO dyes as an interstrand Förster resonance energy transfer pair. siRNA double strands show red emission and a short donor lifetime as readout, whereas siRNA antisense single strands show green emission and a long donor lifetime. This readout signals if GFP silencing can be expected (green) or not (red). We attached both dyes to three structurally different alkyne anchors by postsynthetic modifications. There is only a slight preference for the ribofuranoside anchors with the dyes at their 2’-positions. For the first time, the delivery and fate of siRNA in live HeLa cells was tracked by fluorescence lifetime imaging microscopy (FLIM), which revealed a clear relationship between intracellular transport using different transfection methods and knockdown of GFP expression, which demonstrates the potential of our siRNA architectures as a tool for future development of effective siRNA.     

Prevention of Bone Destruction by Mechanical Loading Is Not Enhanced by the Bruton’s Tyrosine Kinase Inhibitor CC-292 in Myeloma Bone Disease

Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton’s tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.