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Fast radio bursts (FRBs) last for milliseconds and arrive at Earth from cosmological distances. Although their origins and emission mechanisms are unknown, their signals bear similarities with the much less luminous radio emission generated by pulsars within our Miky Way Galaxy1, with properties suggesting neutron star origins2,3. However, unlike pulsars, FRBs typically show minimal variability in their linear polarization position angle (PA) curves4. Even when marked PA evolution is present, their curves deviate significantly from the canonical shape predicted by the rotating vector model (RVM) of pulsars5. Here we report on FRB 20221022A, detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst project (CHIME/FRB) and localized to a nearby host galaxy (about 65 Mpc), MCG+14-02-011. This FRB shows a notable approximately 130° PA rotation over its about 2.5 ms burst duration, resembling the characteristic S-shaped evolution seen in many pulsars and some radio magnetars. The observed PA evolution supports magnetospheric origins6, 7–8over models involving distant shocks9, 10–11, echoing similar conclusions drawn from tempo-polarimetric studies of some repeating FRBs12,13. The PA evolution is well described by the RVM and, although we cannot determine the inclination and magnetic obliquity because of the unknown period or duty cycle of the source, we exclude very short-period pulsars (for example, recycled millisecond pulsars) as the progenitor.

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light years1. The nature of their progenitors and their emission mechanism remain open astrophysical questions2. Here we report the detection of the multicomponent FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components, with a significance of 6.5σ. The long (roughly 3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere3,4, as opposed to emission regions located further away from the star, as predicted by some models5.

Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline from in silicoto analytical and in vitroto overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion channel LRRC8A as a critical component for cisplatin resistance. LRRC8A’s cisplatin-specificity was verified by testing free as well as nanoformulated paclitaxel or doxorubicin. The clinical relevance of LRRC8A was demonstrated by its differential expression in a cohort of 500 head and neck cancer patients, correlating with patient survival under cisplatin therapy. To overcome LRRC8A-mediated cisplatin resistance, we constructed cisplatin-loaded, polysarcosine-based core cross-linked polymeric NPs (NPCis, Ø ∼ 28 nm) with good colloidal stability, biocompatibility (low immunogenicity, low toxicity, prolonged in vivocirculation, no complement activation, no plasma protein aggregation), and low corona formation properties. 2D/3D-spheroid cell models were employed to demonstrate that, in contrast to standard of care cisplatin, NPCissignificantly (p< 0.001) eradicated all cisplatin-resistant cells by circumventing the LRRC8A-transport pathway viathe endocytic delivery route. We here identified LRRC8A as critical for cisplatin resistance and suggest LRRC8A-guided patient stratification for ongoing or prospective clinical studies assessing therapy resistance to nanoscale platinum drug nanoformulations versus current standard of care formulations.

Object Linking and Embedding (OLE) is getting lots of attention these days from both the computer press and application developers, but Dynamic Data Exchange (DDE) is still the primary standard […]

G protein-coupled receptors (GPCRs) constitute the largest family among mammalian membrane proteins and are capable of initiating numerous essential signaling cascades. Various GPCR-mediated pathways are organized into protein microdomains that can be orchestrated and regulated through scaffolding proteins, such as PSD-95/discs-large/ZO1 (PDZ) domain proteins. However, detailed binding characteristics of PDZ–GPCR interactions remain elusive because these interactions seem to be more complex than previously thought. To address this issue, we analyzed binding modalities using our established model system. This system includes the 13 individual PDZ domains of the multiple PDZ domain protein 1 (MUPP1; the largest PDZ protein), a broad range of murine olfactory receptors (a multifaceted gene cluster within the family of GPCRs), and associated olfactory signaling proteins. These proteins were analyzed in a large-scale peptide microarray approach and continuative interaction studies. As a result, we demonstrate that canonical binding motifs were not overrepresented among the interaction partners of MUPP1. Furthermore, C-terminal phosphorylation and distinct amino acid replacements abolished PDZ binding promiscuity. In addition to the described in vitroexperiments, we identified new interaction partners within the murine olfactory epithelium using pull-down-based interactomics and could verify the partners through co-immunoprecipitation. In summary, the present study provides important insight into the complexity of the binding characteristics of PDZ–GPCR interactions based on olfactory signaling proteins, which could identify novel clinical targets for GPCR-associated diseases in the future.

The SlipReactionFoamSintering (SRFS)‐ process is a metallurgical method to produce open‐cell metallic foams of iron based materials, steels and nickel based materials. In this process several chemical reactions take place. Through the most influential parameter, the morphology of the metallic powder, different properties of the foam can be adjusted, such as the viscosity of the slip, the cell structure and the mechanical properties. Several examples are presented in this paper. Moreover, the thermal conductivity of three foams is measured with the transient‐heat‐source‐technique.

Quadratic response surface modeling was used to estimate the optimum combination of feeding rate and percentage of dietary protein for growth of 3–6-week-old blue tilapia Tilapia aurea. Sixteen treatments consisting of all combinations of four dietary protein levels and four feeding rates were replicated in a recirculating-water aquarium system at 23°C for 3 weeks. Quadratic response surfaces fitted to the data were similar for the two replicates and identified treatment combinations supporting maximum growth. Dietary protein, feeding rate, and their interaction significantly affected food conversion by blue tilapia. The quadratic response surface model yielded results that generally agreed with published values for juvenile tilapias. This approach offers a promising research pathway to project optimum culture conditions from short-term trials.