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A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to propose new ...conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii) the mechanical properties – stiffness and strength – are experimentally measured, evaluated, and compared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants.
We present a conceptual bio-engineering design methodology for new biomedical lattices produced by additive manufacturing, which addresses some of the critical points in currently existing porous implant materials. Amongst others: (i) feasibility and accuracy of manufacturing, (ii) design to the elastic properties of bone, and (iii) sensible pores sizes for osseointegration. This has inspired new and novel geometrical latticed designs which aim at improving the properties of intervertebral fusion devices. In their fundamental form, these structures are here fabricated and tested. When integrated into medical devices, these concepts could offer superior medical outcomes.
The processing regime relevant to superplasticity in the Ti–6Al–4V alloy is identified. The effect is found to be potent in the range 850–900°C at strain rates between 0.001/s and 0.0001/s. Within ...this regime, mechanical behaviour is characterised by steady-state grain size and negligible cavity formation; electron backscatter diffraction studies confirm a random texture, leaving grain-boundary sliding as the overarching deformation mechanism. Outside of the superplastic regime, grain size refinement involving recrystallisation and the formation of voids and cavities cause macroscopic softening; low ductility results. Stress hardening is correlated to grain growth and accumulation of dislocations. The findings are used to construct a processing map, on which the dominant deformation mechanisms are identified. Physically-based constitutive equations are presented which are faithful to the observed deformation mechanisms. Internal state variables are used to represent the evolution of grain size, dislocation density and void fraction. Material constants are determined using genetic-algorithm optimisation techniques. Finally, the deformation behaviour of this material in an industrially relevant problem is simulated: the inflation of diffusion-bonded material for the manufacture of hollow, lightweight structures.
Although olfactory mucosa possesses long-lived horizontal basal stem cells (HBCs) and remarkable regenerative capacity, the function of human olfactory neuroepithelium is significantly impaired in ...chronic inflammatory rhinosinusitis. Here, we show that, while inflammation initially damages olfactory neurons and activates HBC-mediated regeneration, continued inflammation locks HBCs in an undifferentiated state. Global gene expression in mouse HBCs reveals broad upregulation of NF-κB-regulated cytokines and chemokines including CCL19, CCL20, and CXCL10, accompanied by enhancement of “stemness”-related transcription factors. Loss-of-function studies identify an NF-κB-dependent role of HBCs in amplifying inflammatory signaling, contributing to macrophage and T cell local proliferation. Chronically activated HBCs signal macrophages to maintain immune defense and prevent Treg development. In diseased human olfactory tissue, activated HBCs in a P63+ undifferentiated state similarly contribute to inflammation through chemokine production. These observations establish a mechanism of chronic rhinosinusitis-associated olfactory loss, caused by a functional switch of neuroepithelial stem cells from regeneration to immune defense.
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•NF-κB-mediated signals in HBCs direct immune cell infiltration and proliferation•Chronic inflammation blocks HBC regeneration and enhances stemness•HBC signaling activates macrophages, inhibiting local Treg development•Olfactory inflammation in humans is associated with neural stem cell dysfunction
Chen et al. identify the immune function of long-lived olfactory stem cells to regulate inflammatory cell recruitment and local proliferation by releasing cytokines and chemokines. Chronically activated stem cells shut down regenerative function and signal macrophages to maintain epithelial immune defense.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the ...pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords “COVID-19,” “smell,” and/or “olfaction.” We included any study that quantified smell loss (anosmia and hyposmia) as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss—subjective measures, such as self-reported smell loss, versus objective measures using rated stimuli—to determine if prevalence differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbances. We identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 objective and 28 subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4–89.2%) and 44% with subjective measurements (95% CI of 32.2–57.0%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.
Design rules are proposed by which the compositions of nickel-based single crystal superalloys can be chosen systematically, using models for the most important characteristics: creep resistance, ...microstructural stability, castability, density and cost. Application of the rules allows the very large compositional space to be reduced to just a few ideal compositions, which are likely to be close to the optimal ones. The procedures have the potential to remove much of the traditional reliance placed upon empiricism and trial-and-error-based testing. It appears that trade-offs must be accepted, however; for example, the most creep-resistant alloys are more dense, more costly and more inherently susceptible to casting-related defects such as freckles during processing. Compositions suitable for both jet propulsion and land-based applications are proposed, for future experimental testing.
The oxidation resistance of three prototype single-crystal nickel-based superalloys for industrial (electricity-generating) gas turbine applications is studied. All contain greater quantities of Cr ...than in most existing single-crystal superalloys; two are alloyed with Si. All alloys are found to be marginal Al
2O
3-formers, with the performance being better at 1000
°C rather than 900
°C, and when Si is added. Microstructural analysis indicates that the ability to form an Al
2O
3 layer is better in the interdendritic regions; the dendritic regions are prone to internal oxidation. In all cases, an outer scale of Cr
2O
3 is formed which is in contact with either Ta
2O
5 (at 1000
°C) or NiTa
2O
6 (at 900
°C). To explain the results, the factors known to influence the rate of Al
2O
3 scale formation are considered. A model is developed to predict whether any given alloy composition will form a continuous Al
2O
3 scale. This is used to rationalize the dependence of Al
2O
3 scale formation on alloy composition in these systems. It is useful for the purposes of alloy design.
The integumentary (i.e., skin) and gustatory systems both function to protect the human body and are a first point of contact with poisons and pathogens. These systems may share a similar protective ...mechanism because, as we show here, both human taste and skin cells express mRNA for bitter 'taste' receptors (TAS2Rs). We used gene-specific methods to measure mRNA from all known bitter receptor genes in adult human skin from freshly biopsied samples and from samples collected at autopsy from the Genotype-Tissue Expression project. Human skin expressed some but not all TAS2Rs, and for those that were expressed, the relative amounts differed markedly among individuals. For some TAS2Rs, mRNA abundance was related to presumed sun exposure based on the location from which the skin sample was collected (TAS2R14, TAS2R30, TAS2R42, and TAS2R60), sex (TAS2R3, TAS2R4, TAS2R8, TAS2R9, TAS2R14, and TAS2R60), and age (TAS2R5), although these effects were not large. These findings contribute to our understanding of extraoral expression of chemosensory receptors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A model is proposed for the variation of the yield strength of nickel-based superalloys as a function of chemical composition. Consistent with hardening theory, alloy strength is assumed to be ...proportional to the product of the anti-phase boundary (APB) energy and the square root of the fraction of the strengthening γ′ phase. A relationship is established between the APB energy estimated using a CALPHAD database and predictions from density functional theory. Quantitative estimates of the role played by Ti, Ta, Nb, Cr, W and Mo suggest that these elements have a profound effect on APB energy. A procedure is proposed to enable the strength to be estimated from an initial input of the chemical composition alone. Predictions are made for new multicomponent alloys. Insight is provided into how composition may be isolated for optimal strengthening. However, the size and spacing of the γ′ precipitates is not explicitly predicted or considered; future work must address this.
The present study aimed to determine if salty and sweet taste preferences in children are related to each other, to markers of growth, and to genetic differences.
We conducted a 2-day, single-blind ...experimental study using the Monell two-series, forced-choice, paired-comparison tracking method to determine taste preferences. The volunteer sample consisted of a racially/ethnically diverse group of children, 5-10 years of age (n = 108), and their mothers (n = 83). After excluding those mothers who did not meet eligibility and children who did not understand or comply with study procedures, the final sample was 101 children and 76 adults. The main outcome measures were most preferred concentration of salt in broth and crackers; most preferred concentration of sucrose in water and jelly; reported dietary intake of salty and sweet foods; levels of a bone growth marker; anthropometric measurements such as height, weight, and percent body fat; and TAS1R3 (sweet taste receptor) genotype.
Children preferred higher concentrations of salt in broth and sucrose in water than did adults, and for both groups, salty and sweet taste preferences were significantly and positively correlated. In children, preference measures were related to reported intake of sodium but not of added sugars. Children who were tall for their age preferred sweeter solutions than did those that were shorter and percent body fat was correlated with salt preference. In mothers but not in children, sweet preference correlated with TAS1R3 genotype.
For children, sweet and salty taste preferences were positively correlated and related to some aspects of real-world food intake. Complying with recommendations to reduce added sugars and salt may be more difficult for some children, which emphasizes the need for new strategies to improve children's diets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A physical model for the creep deformation of single crystal superalloys is presented that is sensitive to chemical composition and microstructure. The rate-controlling step is assumed to be climb of ...dislocations at the matrix/particle interfaces and their rate of escape from trapped configurations; a strong dependence on alloy composition then arises. By testing the predictions of the model against the considerable body of published experimental data, the dependence of the kinetics of creep deformation on alloy chemistry is rationalized. The effects of microstructural scale – precipitate size, geometry and spacing – are also studied. The climb processes assumed at the matrix/precipitate interfaces give rise to the vacancy flux required for the mass transport needed for rafting. For creep deformation at higher temperatures, a modification to the basic theory is proposed to account for a rafting-induced strengthening effect. A first-order estimate for the rate of creep deformation emerges from the model, which is useful for the purposes of alloy design.
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