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Air quality in transportation vehicle cabins is becoming a major concern due to increasing exposure of drivers to harmful gases and aerosol, especially if having in mind that that safety and pollution are positively correlated and adverse events. In order to reduce exposure to air pollution, there is ongoing development of air filters in modern heavy-duty vehicles and increase in protective regulations throughout the world. The aim of this study is to gain insight into extent of pollutants in heavy-duty vehicle cabins, in which drivers spend a large amount of their working (and spare) time, and the necessity for use of air filtration systems. Both experimental results and modelling approach applied in this manuscript reveal the importance of filtration of cabin air, and indicate good correlation between experimental and mathematical results from field measurements conducted in a highly polluted city. Namely, this paper reveals excellent results with the HECA filter which have potential to significantly reduce pollution in the cabin.

Wall slip or, more usually, liquid-solid phase separation at the boundary wall when measuring the rheological properties of particulate suspensions is normally considered an undesirable source of error. However, exclusion of a structure consisting of multiple particulates at a planar boundary can, in turn, reveal the nature of that structure and the way it interacts with other elements in the dispersion. Using a system of surface-treated ground calcite particles, designed to control lyophilicity, dispersed, respectively, in two comparative liquids, hexadecane (dispersive surface tension component only) and linseed oil (both dispersive and polar surface tension components), the relative wettability of the particulate surface can be studied. The static state is viscoelastic, with the elastic component reflecting the network of interacting forces acting to structure the particles together and/or to trap liquid within the long-range particle-particle matrix. As strain is applied under plate-plate geometry, selected aggregate structures become size-excluded at the wall, leading to a loss of shear coupling with the bulk polydisperse suspension. At high strain, given optimal solids content, this results in a stochastic transition between two discrete stress data sets, i.e. that with full shear coupling and that with only partial coupling. Stress recovery is subsequently monitored as strain is step-wise reduced, and the progress toward loss of the stochastic transient phenomenon, together with its parallel change in magnitude, is used to describe the re-formation of primary agglomerates. Cessation of the phase separation indicates re-build of the close-to-static structure. Under certain conditions it is observed that the cessation may be accompanied by a secondary relaxation of state, indicating the build of a secondary but weaker structure, likened to the well-known dual-level flocculation in aqueous colloidal suspension. Rheo-optical observations using small angle light scattering illumination (SALS) are used to confirm a structure model switching from static (uncoupled with shear) to rotating (fully coupled to the boundary-defined shear) and finally uniformly sheared.

Novel-produced never-dried and dried microcrystalline cellulose (MCC) was previously compared with a commercial MCC. The novel MCC was shown to be a suitable starting material for producing cellulose nanofibrils, in turn having similar molecular weight Mw, crystallinity, and particle size comparable to those from sequentially enzymatic and mechanically treated softwood sulphite pulp, but at lower cost. The study here presents a rheological parameterisation of the aqueous suspension throughout the process, aimed at delivering a correlation between specific surface area, at equal material particle size, and adsorptive coupling between neighbouring cellulose particles and interstitial water under flow. We conclude that combining dynamic viscosity with an independent measure of particle size provides a suitable quality control of MCC-derived cellulose nanofibrils, obviating the need for individual property-raw material relationships to be evaluated, and this principle may provide a generalised method for use in the production of cellulose nanofibrils.

Plant root-nodule symbiosis (RNS) with mutualistic nitrogen-fixing bacteria is restricted to a single clade of angiosperms, the Nitrogen-Fixing Nodulation Clade (NFNC), and is best understood in the legume family. Nodulating species share many commonalities, explained either by divergence from a common ancestor over 100 million years ago or by convergence following independent origins over that same time period. Regardless, comparative analyses of diverse nodulation syndromes can provide insights into constraints on nodulation-what must be acquired or cannot be lost for a functional symbiosis-and the latitude for variation in the symbiosis. However, much remains to be learned about nodulation, especially outside of legumes. Here, we employed a large-scale phylogenomic analysis across 88 species, complemented by 151 RNA-seq libraries, to elucidate the evolution of RNS. Our phylogenomic analyses further emphasize the uniqueness of the transcription factor NIN as a master regulator of nodulation and identify key mutations that affect its function across the NFNC. Comparative transcriptomic assessment revealed nodule-specific upregulated genes across diverse nodulating plants, while also identifying nodule-specific and nitrogen-response genes. Approximately 70% of symbiosis-related genes are highly conserved in the four representative species, whereas defense-related and host-range restriction genes tend to be lineage specific. Our study also identified over 900 000 conserved non-coding elements (CNEs), over 300 000 of which are unique to sampled NFNC species. NFNC-specific CNEs are enriched with the active H3K9ac mark and are correlated with accessible chromatin regions, thus representing a pool of candidate regulatory elements for genes involved in RNS. Collectively, our results provide novel insights into the evolution of nodulation and lay a foundation for engineering of RNS traits in agriculturally important crops.

Skeletal muscle stem and progenitor cells including those derived from human pluripotent stem cells (hPSCs) offer an avenue towards personalized therapies and readily fuse to form human-mouse myofibres in vivo. However, skeletal muscle progenitor cells (SMPCs) inefficiently colonize chimeric stem cell niches and instead associate with human myofibres resembling foetal niches. We hypothesized competition with mouse satellite cells (SCs) prevented SMPC engraftment into the SC niche and thus generated an SC ablation mouse compatible with human engraftment. Single-nucleus RNA sequencing of SC-ablated mice identified the absence of a transient myofibre subtype during regeneration expressing Actc1. Similarly, ACTC1+ human myofibres supporting PAX7+ SMPCs increased in SC-ablated mice, and after re-injury we found SMPCs could now repopulate into chimeric niches. To demonstrate ACTC1+ myofibres are essential to supporting PAX7 SMPCs, we generated caspase-inducible ACTC1 depletion human pluripotent stem cells, and upon SMPC engraftment we found a 90% reduction in ACTC1+ myofibres and a 100-fold decrease in PAX7 cell numbers compared with non-induced controls. We used spatial RNA sequencing to identify key factors driving emerging human niche formation between ACTC1+ myofibres and PAX7+ SMPCs in vivo. This revealed that transient regenerating human myofibres are essential for emerging niche formation in vivo to support PAX7 SMPCs.

A novel method is introduced to describe quantitatively hysteresis seen in flow curves of microfibrillated cellulose suspensions. Also, a data normalisation procedure is presented that allows a direct comparison of data from suspensions of different solids contents. The discussion of the flow curve hysteresis of an MFC suspension is proposed to provide a lot of information on the suspension morphology under flow. Such information is not only useful for process design, but also may serve as a quality control tool. Hysteresis data as a function of the suspension solids content are provided, and considered with reference to an overview made of peer work in the field. Two discrete hysteresis loop areas were found in the flow curves presented in this work, each associated with a distinct shear rate region, one where the viscosity of the flow curve during shear rate increase is higher than that of the shear rate flow curve at decreasing shear rate (named positive hysteresis) and another where it is the opposite (named negative hysteresis). This behavior seems to have been rarely reported, and where reported we offer an explanation, based on morphological models and rheometer measurement set up, as to why other researchers may find a variety of hysteresis forms. It is hypothesised that the negative normalised hysteresis is mainly depending on the excessive flocculation/structuration induced at intermediate shear rates during the shear rate increase, and that it is necessarily less with increasing solids content because of the reduced availability of free water. The positive normalised hysteresis, however, is considered to originate from the different morphologies at lower shear rates, i.e. the initial, homogeneous structure vs. the structure that was previously induced by the intermediate shear during shear rate decrease. The positive normalised hysteresis appears not to depend on the solids content, indicating a self-similarity or scaling behavior of the structuring with respect to the underlying network structure.

Phase-separable particulate-containing gel structures constitute complex fluids. In many cases they may incorporate component concentration inhomogeneities within the ensemble matrix. When formulated into high consistency suspensions, these can lead to unpredictable time-dependent variations in rheological response, particularly under shear in simple parallel plate and cylindrical rotational geometries. Smoothing function algorithms are primarily designed to cope with random noise. In the case studied here, namely nanocellulose-based high consistency aqueous suspensions, the system is not randomised but based on a series of parallel and serial spatial and time related mechanisms. These include: phase separation, wall slip, stress relaxation, breakdown of elastic structure and inhomogeneous time-dependent and induced structure rebuild. When vacuum dewatering is applied to such a suspension while under shear, all these effects are accompanied by the development of an uneven solid content gradient within the sample, which further adds to transitional phenomena in the recorded rheological data due to spatial and temporal differences in yield stress distribution. Although these phenomena are strictly speaking not noise, it is nevertheless necessary to apply relevant data smoothing in order to extract apparent/process viscosity parameters in respect to averaging across the structural ensemble. The control parameters in the measurement of the rheological properties, to which smoothing is applied, are focused on parallel plate gap, surface geometry, shear rate, oscillation frequency and strain variation, and relaxation time between successive applications of strain. The smoothing algorithm follows the Tikhonov regularisation procedure.

Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

The formulation of the problem in this study is that there is a phenomenon that occurs in the field that the housing and settlement area services of South Sumatra Province have problems such as minimal employee motivation due to demands to fulfill their rights and obligations as state civil servants, as well as a decreased level of enthusiasm so that it becomes an obstacle for the realization of the performance process in completing the work given. This study aims to determine the motivation and competence of the employees of the Department of Housing and Residential Areas of South Sumatra Province. Sampling of 53 respondents in this study using simple random sampling technique. The data analysis technique used multiple linear analysis with the help of the IBM SPSS 22 program. The results obtained both partially and simultaneously that work motivation and competence have a positive and significant effect on employee performance in the Housing and Settlement Area Office of South Sumatra Province.

Cellulose is a strong contender for the development of sustainably resourced biodegradable material composites supporting circular economy. Nanofibrillar cellulose-comprising materials are among the most promising lignocellulose derivatives. Currently, their production capacity and economy are hindered by high chemical and energy consumption, the latter primarily during mechanical fibrillation of native fiber in aqueous suspension and the negative limitation of very low solid content associated with the gel-like properties of the resulting final product. The application of oxygen gas barrier discharge (DBD) plasma on dry cellulose fiber, as reported here, is considered novel in achieving onward nanofibrillation. At this early stage, though, simple laboratory DBD equipment precludes the study of overall efficiency. Example fiber was taken from paper pulp manufacture but may not be limited to wood source. The oxygen plasma was seen to etch the microcellulose fiber structure, simultaneously oxidizing the glue-functioning hemicellulose, rendering it soluble, so that nanopolymer crystalline-based cellulose fibrils can be readily released at the surface of the host refined microfiber at the point of application, forming micro nanofibrillated cellulose structure (MNFC) at previously uneconomic higher solid content. Eliminating the need for liquid water during precursor process treatment is considered potentially transformative with respect to production feasibility, end-product transportation and application.

Duchenne muscular dystrophy (DMD) is caused by an out-of-frame mutation in the DMD gene that results in the absence of a functional dystrophin protein, leading to a devastating progressive lethal muscle-wasting disease. Muscle stem cell-based therapy is a promising avenue for improving muscle regeneration. However, despite the efforts to deliver the optimal cell population to multiple muscles most efforts have failed. Here we describe a detailed optimized method of for the delivery of human skeletal muscle progenitor cells (SMPCs) to multiple hindlimb muscles in healthy, dystrophic and severely dystrophic mouse models. We show that systemic delivery is inefficient and is affected by the microenvironment. We found that significantly less human SMPCs were detected in healthy gastrocnemius muscle cross-sections, compared to both dystrophic and severely dystrophic gastrocnemius muscle. Human SMPCs were found to be detected inside blood vessels distinctly in healthy, dystrophic and severely dystrophic muscles, with prominent clotting identified in severely dystrophic muscles after intra arterial (IA) systemic cell delivery. We propose that muscle microenvironment and the severity of muscular dystrophy to an extent impacts the systemic delivery of SMPCs and that overall systemic stem cell delivery is not currently efficient or safe to be used in cell based therapies for DMD. This work extends our understanding of the severe nature of DMD, which should be taken into account when considering stem cell-based systemic delivery platforms.

Duchenne muscular dystrophy (DMD) is caused by out-of-frame mutations in the DMD gene resulting in the absence of a functional dystrophin protein, leading to a devastating and progressive lethal muscle-wasting disease. Little is known about cellular heterogeneity as disease severity increases. Advances in single-cell RNA sequencing (scRNA-seq) enabled us to explore skeletal muscle-resident cell populations in healthy, dystrophic, and severely dystrophic mouse models. We found increased frequencies of activated fibroblasts, fibro-adipogenic progenitor cells, and pro-inflammatory macrophages in dystrophic gastrocnemius muscles and an upregulation of extracellular matrix genes on endothelial cells in dystrophic and severely dystrophic muscles. We observed a pronounced risk of clotting, especially in the severely dystrophic mice with increased expression of plasminogen activator inhibitor-1 in endothelial cells, indicating endothelial cell impairment as disease severity increases. This work extends our understanding of the severe nature of DMD which should be considered when developing single or combinatorial approaches for DMD.

Abstract Background Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. Methods The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. Results Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. Conclusion Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA

Objectives: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesions. In addition, to investigate pathophysiological changes based on imaging and biomarker measures. Methods: Using a single-case experimental design, a total of 12 participants were randomly allocated in 4 equal groups of 3 to receive different dosages of focused-extracorporeal shock wave therapy. Each group received either 4 or 6 sessions of 1500 or 3000 shocks over 4 or 6 weekly sessions. Participants underwent repeated measurements during the baseline, intervention, and post-intervention phases for Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, aggregated locomotor function score and pressure pain threshold. Imaging and inflammatory biomarker outcomes were measured at baseline and 3 months following the intervention. Results: The group receiving the highest dosage of focused-extracorporeal shock wave therapy showed clinical improvements superior to those of participants in the other 3 groups. Statistically significant changes during the follow-up phase in contrast to baseline measurements for the WOMAC score (Tau-U= –0.88, p

There is little empirical research related to how elementary students develop computational thinking (CT) and how they apply CT in problem-solving. To address this gap in knowledge, this study made use of learning trajectories (LTs; hypothesized learning goals, progressions, and activities) in CT concept areas such as sequence, repetition, conditionals, and decomposition to better understand students' CT. This study implemented eight math-CT integrated lessons aligned to U.S. national mathematics education standards and the LTs with third- and fourth-grade students. This basic interpretive qualitative study aimed at gaining a deeper understanding of elementary students' CT by having students express and articulate their CT in cognitive interviews. Participants' (n = 22) CT articulation was examined using "a priori" codes translated verbatim from the learning goals in the LTs and was mapped to the learning goals in the LTs. Results revealed a range of students' CT in problem-solving, such as using precise and complete problem-solving instructions, recognizing repeating patterns, and decomposing arithmetic problems. By collecting empirical data on how students expressed and articulated their CT, this study makes theoretical contributions by generating initial empirical evidence to support the hypothesized learning goals and progressions in the LTs. This article also discusses the implications for integrated CT instruction and assessments at the elementary level.