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The use of toxic Cr (VI) in the chrome plating process poses significant health risks, highlighting the urgent need to find sustainable alternatives for many applications such as cold rolling. Understanding key properties of functional chrome coating in lubricated industrial processes, especially its wetting properties that can support lubrication, low friction, and durability, is essential for the development of safer coating processes. However, the wetting properties of hard chromium coating are not fully understood. This study investigates the wetting characteristics of chromium coatings in comparison to uncoated steel. The study explores the dynamic wetting behavior by conducting contact angle measurements with water and lubricant oil, determining surface free energy using the sessile drop method, and characterizing the surface through X-ray photoelectron spectroscopy analysis. The findings reveal that a standard hard chrome coating exhibits superior wettability by both water and oil and higher surface energy compared to uncoated steel. The research, supported by theoretical modelling, highlights that factors are not limited to chromium alone, but rather involve a multilayer system that includes chromium oxide and organic contaminations, which have a substantial impact on surface properties and wettability. Increased levels of organic contamination on the chrome-coated surface, are shown to result in weaker intermolecular interactions with the contacting fluid, leading to reduced surface affinity to water and consequently result in higher contact angles. Our findings provide critical insights into the intricate nature of chromium coatings and lay foundations for developing sustainable alternatives.

Fibrotic remodeling is the primary driver of functional loss in chronic kidney disease, with no specific anti-fibrotic agent available for clinical use. Transglutaminase 2 (TG2), a wound response enzyme that irreversibly crosslinks extracellular matrix proteins causing dysregulation of extracellular matrix turnover, is a well-characterized anti-fibrotic target in the kidney. We describe the humanization and characterization of two anti-TG2 monoclonal antibodies (zampilimab [hDC1/UCB7858] and BB7) that inhibit crosslinking by TG2 in human in vitro and rabbit/cynomolgus monkey in vivo models of chronic kidney disease. Determination of zampilimab half-maximal inhibitory concentration (IC50) against recombinant human TG2 was undertaken using the KxD assay and determination of dissociation constant (Kd) by surface plasmon resonance. Efficacy in vitro was established using a primary human renal epithelial cell model of tubulointerstitial fibrosis, to assess mature deposited extracellular matrix proteins. Proof of concept in vivo used a cynomolgus monkey unilateral ureteral obstruction model of chronic kidney disease. Zampilimab inhibited TG2 crosslinking transamidation activity with an IC50 of 0.25 nM and Kd of 50%, with no safety signals. Our data support the clinical investigation of zampilimab for the treatment of kidney fibrosis.

Summary: Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen.

We report multiwavelength observations and characterization of the ultraluminous transient AT 2021lwx (ZTF20abrbeie; aka “Barbie”) identified in the alert stream of the Zwicky Transient Facility (ZTF) using a Recommender Engine For Intelligent Transient Tracking filter on the ANTARES alert broker. From a spectroscopically measured redshift of 0.995, we estimate a peak-observed pseudo-bolometric luminosity of log( ${L}_{\max }/[\mathrm{erg}\,{{\rm{s}}}^{-1}]$ ) = 45.7 from slowly fading ztf- g and ztf- r light curves spanning over 1000 observer-frame days. The host galaxy is not detected in archival Pan-STARRS observations ( g > 23.3 mag), implying a lower limit to the outburst amplitude of more than 5 mag relative to the quiescent host galaxy. Optical spectra exhibit strong emission lines with narrow cores from the H Balmer series and ultraviolet semi-forbidden lines of Si iii ] λ 1892, C iii ] λ 1909, and C ii ] λ 2325. Typical nebular lines in Active Galactic Nucleus (AGN) spectra from ions such as [O ii ] and [O iii ] are not detected. These spectral features, along with the smooth light curve that is unlike most AGN flaring activity and the luminosity that exceeds any observed or theorized supernova, lead us to conclude that AT 2021lwx is most likely an extreme tidal disruption event (TDE). Modeling of ZTF photometry with MOSFiT suggests that the TDE was between a ≈14 M _⊙ star and a supermassive black hole of mass M _BH ∼ 10 ^8 M _⊙ . Continued monitoring of the still-evolving light curve along with deep imaging of the field once AT 2021lwx has faded can test this hypothesis and potentially detect the host galaxy.

It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.

Motor learning underpins successful motor skill acquisition. Although it is well known that pain changes the way we move, it's impact on motor learning is less clear. The aim of this systematic review was to synthesize evidence on the impact of experimental and clinical pain on task performance and activity-dependent plasticity measures across learning and explore these findings in relation to different pain and motor learning paradigms. Five databases were searched: Web of Science, Scopus, MEDLINE, Embase and CINAHL. Two reviewers independently screened the studies, extracted data, and assessed risk of bias using the Cochrane ROB2 and ROBIN-I. The overall strength of evidence was rated using the GRADE guidelines. Due to the heterogeneity of study methodologies a narrative synthesis was employed. Twenty studies were included in the review: fifteen experimental pain and five clinical pain studies, covering multiple motor paradigms. GRADE scores for all outcome measures suggested limited confidence in the reported effect for experimental pain and clinical pain, on motor learning. There was no impact of pain on any of the task performance measures following acquisition except for 'accuracy' during a tongue protrusion visuomotor task and 'timing of errors' during a motor adaptation locomotion task. Task performance measures at retention, and activity dependent measures at both acquisition and retention showed conflicting results. This review delivers a detailed synthesis of research studies exploring the impact of pain on motor learning. This is despite the challenges provided by the heterogeneity of motor learning paradigms, outcome measures and pain paradigms employed in these studies. The results highlight important questions for further research with the goal of strengthening the confidence of findings in this area.

This paper reports a series of experimental and modeling investigations on two piezoelectric arrays made of polyvinylidene fluoride (PVDF) films. They were embedded inside rubber cylinders and used to directly measure the internal stresses generated by various external excitations applied to the top surface of the cylinder. Corresponding finite element (FE) models were established to reveal the relationship between the PVDF output and the stress field applied to it. This research improves the understanding of the output mechanism of the embedded PVDF and provides useful information for the design of PVDF sensors.

Introduction Motor skill learning is intrinsic to living. Pain demands attention and may disrupt non-pain-related goals such as learning new motor skills. Although rehabilitation approaches have used motor skill learning for individuals in pain, there is uncertainty on the impact of pain on learning motor skills.Methods and analysis The protocol of this systematic review has been designed and is reported in accordance with criteria set out by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Web of Science, Scopus, MEDLINE, Embase and CINAHL databases; key journals; and grey literature will be searched up until March 2021, using subject-specific searches. Two independent assessors will oversee searching, screening and extracting of data and assessment of risk of bias. Both behavioural and activity-dependent plasticity outcome measures of motor learning will be synthesised and presented. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and dissemination No patient data will be collected, and therefore, ethical approval was not required for this review. The results of this review will provide further understanding into the complex effects of pain and may guide clinicians in their use of motor learning strategies for the rehabilitation of individuals in pain. The results of this review will be published in a peer-reviewed journal and presented at scientific conferences.PROSPERO registration number CRD42020213240.

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.

Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system, we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020 and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 61.9% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with a marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation.

There was a time not all that long ago when what is now known as medievalism was largely disregarded, so I take it as a mark of distinction to have my book Medievalism: A Critical History scrutinised as closely as it has been and given such generous attention by Richard Utz. As a still somewhat inchoate field, medievalism is still a volatile and changeable one. The following remarks are offered more in the spirit of keeping a critical conversation going within that context, than out of any desire to correct or to “get it right”.

The vast majority of clinically approved protein kinase inhibitors target the ATP-binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects. Allosteric inhibitors are generally more selective, but are difficult to identify because allosteric binding sites are often unknown or poorly characterized. Aurora-A is activated through binding of TPX2 to an allosteric site on the kinase catalytic domain, and this knowledge could be exploited to generate an inhibitor. Here, we generated an allosteric inhibitor of Aurora-A kinase based on a synthetic, vNAR single domain scaffold, vNAR-D01. Biochemical studies and a crystal structure of the Aurora-A/vNAR-D01 complex show that the vNAR domain overlaps with the TPX2 binding site. In contrast with the binding of TPX2, which stabilizes an active conformation of the kinase, binding of the vNAR domain stabilizes an inactive conformation, in which the αC-helix is distorted, the canonical Lys-Glu salt bridge is broken and the regulatory (R-) spine is disrupted by an additional hydrophobic side chain from the activation loop. These studies illustrate how single domain antibodies can be used to characterize the regulatory mechanisms of kinases and provide a rational basis for structure-guided design of allosteric Aurora-A kinase inhibitors.

A major contributor to longitudinal vibration in marine propulsion systems is propeller induced excitation. This constitutes a key source of underwater acoustical radiation through excitation of the hull. Understanding this hydrodynamic force at the interface of the thrust bearing is important in order to develop an accurate vibrational model of the propulsion system and in determining potential control mechanisms. In order to investigate the thrust force during operation of a propulsion system, Polyvinylidene Fluoride (PVDF) was embedded into the stationery collar inside a custom thrust bearing in a scaled model of a typical propulsion system. The number of blades of the propeller and its rotational speed were altered to obtain an understanding of the characteristic vibrations of the shaft propulsion system. The rig comprised of the propeller, shaft, journal bearings and a thrust bearing. A two and three blade propeller and a four, five and six pad bearing were tested. A strain gauge and accelerometer were used to infer the propeller force and enable comparison with the PVDF signals. As a result of the asymmetrical flow around the propeller, the blade passing frequencies (BPF) are clearly observed. This frequency contribution was present at all speeds tested. The PVDF signal also showed significant pad passing frequency (PPF) and BPF and modulation of both.