Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that ...pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.
•Ischemic cardiac tissue is replaced with a fibrotic scar.•The classical role of resident cardiac fibroblasts is the deposition of scar tissue.•Fibroblasts play a wide variety of roles in ischemic ...cardiac remodeling.•Fibroblasts interact with other cardiac cell types in the ischemic heart.•Fibroblasts contribute to each of the various phases of the injury response.
•Amorphous powder of Fe-Si-B-Nb-Cu alloy was produced by helium gas atomisation.•Proper annealing resulted in structural relaxation and nanocrystallisation.•Powder cores were manufactured using the ...as-atomised and annealed powders.•Cores exhibit excellent low coercivity and low core losses.•The small particle size and good insulation can explain the low core losses.
The present work demonstrates the high-frequency core loss performance of Fe-based amorphous and nanocrystalline powder cores, initially produced by gas atomised powder, consolidated using sieved particles ≤20 µm, and isolated by a precise insulating layer of polymer to limit the inter- and intra-particle eddy currents to attain enhanced performance. The large glass forming ability (GFA) of the gas atomised powder, reflected by different glass forming instruments, such as the supercooled region (ΔTX = 54 °C) and the reduced glass transition temperature (Trg = 0.56), is consistent with the substantial amorphisation capability of the alloy. To the best of our knowledge, this is the first-ever report to reveal a large ΔTX in the Finemet-type alloy powders, an essential parameter to gas-atomise the amorphous powders with significantly lower cooling rates compared to the melt-spun ribbons. Further, subsequent annealing of the amorphous powders, between the exothermic events guided by differential scanning calorimetry (DSC), lead to the growth of a fine nanocrystalline structure of grains ≤15 nm, thanks to the positive enthalpy of mixing of Cu with the constituents to act as a nucleation agent, to retain the excellent soft magnetic properties. The DC soft magnetic properties of the powders were significantly improved on thermal annealing, confirmed by hysteretic loops, quantified by reduced coercivity HC <1 Oe of annealed powders at <575 °C, and attributed to the reduced magnetoelastic contribution due to zero/near-zero magnetostriction anisotropy, attained due to the homogenous nanocrystalline structure. The amorphous and nanocrystalline powder cores, consolidated by compression moulding, show ultra-high loss performance, due to the ultra-low coercivity attained on nanocrystallisation, and negligible eddy currents loss, owning to efficient insulation of small particles, for high-frequency power conversion applications, such as voltage regulator (VR), and resonant converters, in automotive industry and data storage centres.
Fe–Si–B–Nb–Cu alloy powders, with and without P additions, were produced by gas atomization. The particles smaller than 20 μm are fully amorphous, exhibiting good soft magnetic properties. The ...crystallization process was studied by differential scanning calorimetry, demonstrating that its kinetics changes dramatically with small variations in the composition. The (Fe0.76Si0.09B0.10P0.05)97.5Nb2.0Cu0.5 (at. %) alloy was annealed in the supercooled liquid region (480 °C) and at the first crystallization peak (530 °C). The structural characterization by means of differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy provided information that explained the excellent soft magnetic properties. Annealing at 480 °C produced an amorphous relaxed structure with improved soft magnetic properties. At 530 °C, a two-phase material formed by nanocrystals with an average grain size of 16–17 nm embedded in an amorphous matrix was developed. Partial nanocrystallization increased the saturation magnetization from 139 to 144 emu/g and reduced the coercivity from 2.24 to 0.69 Oe. These results can be understood in terms of the algebraic contribution of both phases to the magnetization and the application of the random anisotropy model to nanocrystalline soft magnetic materials.
•Amorphous powder of Fe–Si–B–P–Nb–Cu alloys was produced by He gas atomization.•Proper annealing resulted in structural relaxation and nanocrystallization.•Crystallization kinetics was different depending on composition.•The annealed powders exhibit excellent soft magnetic properties.•Random anisotropy model can explain the very low coercivity.
•Congenital dyserythropoietic anemia type 1 (CDA1) is caused by mutations in CDAN1.•HUDEP2 lines with deletion or mutation of CDAN1 phenocopy CDA1 erythroblasts.•CDAN1 mutant HUDEP2 cells have ...altered histone acetylation and gene expression.
The generation of a functional erythrocyte from a committed progenitor requires significant changes in gene expression during hemoglobin accumulation, rapid cell division, and nuclear condensation. Congenital dyserythropoietic anemia type I (CDA-I) is an autosomal recessive disease that presents with erythroid hyperplasia in the bone marrow. Erythroblasts in patients with CDA-I are frequently binucleate and have chromatin bridging and defective chromatin condensation. CDA-1 is most commonly caused by mutations in Codanin-1 (CDAN1). The function of CDAN1 is poorly understood but it is thought to regulate histone incorporation into nascent DNA during cellular replication. The study of CDA-1 has been limited by the lack of in vitro models that recapitulate key features of the disease, and most studies on CDAN1 function have been done in nonerythroid cells. To model CDA-I we generated HUDEP2 mutant lines with deletion or mutation of R1042 of CDAN1, mirroring mutations found in CDA-1 patients. CDAN1 mutant cell lines had decreased viability and increased intercellular bridges and binucleate cells. Further, they had alterations in histone acetylation associated with prematurely elevated erythroid gene expression, including gamma globin. Together, these data imply a specific functional role for CDAN1, specifically R1042 on exon 24, in the regulation of DNA replication and organization during erythroid maturation. Most importantly, generation of models with specific patient mutations, such as R1042, will provide further mechanistic insights into CDA-I pathology.
The interest and societal demand on the use of natural, biodegradable and renewable resources has increased in the last few years. In addition, food producers and consumers have improved their ...requirements for the quality of processed food, particularly in the field of increasing shelf-life while preserving organoleptic and nutritional properties. Active packaging technologies have greatly developed in the last decade by trying to satisfy the need for long-life processed food in addition to antioxidant/antimicrobial components in the packaging material. These components are intended to be released in a controlled way to food. These rising trends have been reflected in the field of food packaging by the use of chemicals extracted and obtained from plants in active packaging formulations. Herbs and spices have shown great potential to be used as renewable, biodegradable and valuable sources of chemicals, such as polyphenols, with high antioxidant/antimicrobial performance. This review aims to present the latest published work in this area.
Natural additives obtained from herbs and spices are being increasingly used in the food packaging industry.
Blends of poly(lactic acid) (PLA) and poly(3-hydroxybutyrate) (PHB) plasticized with a lactic acid oligomer (OLA) added at three different concentrations (15, 20 and 30 wt% by weight), were prepared ...by an optimized extrusion process to improve the processability and mechanical properties of these biopolymers for flexible film manufacturing. Morphological, chemical, thermal, mechanical, barrier and migration properties were investigated and formulations with desired performance in eco-friendly films were selected. The efficiency of OLA as plasticizer for PLA_PHB blends was demonstrated by the significant decrease of their glass transition temperatures and a considerable improvement of their ductile properties. The measured improvements in the barrier properties are related to the higher crystallinity of the plasticized PLA_PHB blends, while the overall migration test underlined that all the proposed formulations maintained migration levels below admitted levels. The PLA_PHB blend with 30 wt% OLA was selected as the optimum formulation for food packaging, since it offered the best compromise between ductility and oxygen and water vapor barrier properties with practically no migration.
Owing to its excellent soft-tissue contrast, magnetic resonance (MR) imaging has found an increased application in radiation therapy (RT). By harnessing these properties for treatment planning, ...automated segmentation methods can alleviate the manual workload burden to the clinical workflow. We investigated atlas-based segmentation methods of organs at risk (OARs) in the head and neck (H&N) region using one approach that selected the most similar atlas from a library of segmented images and two multi-atlas approaches. The latter were based on weighted majority voting and an iterative atlas-fusion approach called STEPS. We built the atlas library from pre-treatment T1-weighted MR images of 12 patients with manual contours of the parotids, spinal cord and mandible, delineated by a clinician. Following a leave-one-out cross-validation strategy, we measured the geometric accuracy by calculating Dice similarity coefficients (DSC), standard and 95% Hausdorff distances (HD and HD95), and the mean surface distance (MSD), whereby the manual contours served as the gold standard. To benchmark the algorithm, we determined the inter-observer variability (IOV) between three observers. To investigate the dosimetric effect of segmentation inaccuracies, we implemented an auto-planning strategy within the treatment planning system Monaco (Elekta AB, Stockholm, Sweden). For each set of auto-segmented OARs, we generated a plan for a 9-beam step and shoot intensity modulated RT treatment, designed according to our institution's clinical H&N protocol. Superimposing the dose distributions on the gold standard OARs, we calculated dose differences to OARs caused by delineation differences between auto-segmented and gold standard OARs. We investigated the correlations between geometric and dosimetric differences. The mean DSC was larger than 0.8 and the mean MSD smaller than 2 mm for the multi-atlas approaches, resulting in a geometric accuracy comparable to previously published results and within the range of the IOV. While dosimetric differences could be as large as 23% of the clinical goal, treatment plans fulfilled all imposed clinical goals for the gold standard OARs. Correlations between geometric and dosimetric measures were low with R2 < 0.5. The geometric accuracy and the ability to achieve clinically acceptable treatment plans indicate the suitability of using atlas-based contours for RT treatment planning purposes. The low correlations between geometric and dosimetric measures suggest that geometric measures alone are not sufficient to predict the dosimetric impact of segmentation inaccuracies on treatment planning for the data utilised in this study.
Background
The objective of this study was to estimate the association between sleep quality (SQ) and improvements in low back pain (LBP) and disability, among patients treated for LBP in routine ...practice.
Methods
This prospective cohort study included 461 subacute and chronic LBP patients treated in 11 specialized centres, 14 primary care centres and eight physical therapy practices across 12 Spanish regions. LBP, leg pain, disability, catastrophizing, depression and SQ were assessed through validated questionnaires upon recruitment and 3 months later. Logistic regression models were developed to assess: (1) the association between the baseline score for SQ and improvements in LBP and disability at 3 months, and (2) the association between improvement in SQ and improvements in LBP and disability during the follow‐up period.
Results
Seventy‐three per cent of patients were subacute. Median scores at baseline were four points for both pain and disability, as assessed with a visual analog scale and the Roland‐Morris Questionnaire, respectively. Regression models showed (OR 95% CI) that baseline SQ was not associated with improvements in LBP (0.99 0.94; 1.06) or in disability (0.99 0.93; 1.05), although associations existed between ‘improvement in SQ’ and ‘improvement in LBP’ (4.34 2.21; 8.51), and ‘improvement in SQ’ and ‘improvement in disability’ (4.60 2.29; 9.27).
Conclusions
Improvement in SQ is associated with improvements in LBP and in disability at 3‐month follow‐up, suggesting that they may reflect or be influenced by common factors. However, baseline SQ does not predict improvements in pain or disability.
Significance
In clinical practice, sleep quality, low back pain and disability are associated. However, sleep quality at baseline does not predict improvement in pain and disability.
Highlights • Establishing MRI-only RTP workflows requires synthetic CTs for dose calculation. • This study evaluates the feasibility of using a multi-atlas CT synthesis approach. • The proposed ...method was validated on head and neck and prostate cancer patients. • Results showed an accurate bone estimation for future patient positioning. • Results showed that synthetic CTs are suitable to perform clinical dose calculations.
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